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Plasma butyrylcholinesterase concentrations in psittacine birds: reference values, factors of variation, and association with feather-damaging behavior.

Abstract. Butyrylcholinesterase is a glycoprotein enzyme used in the diagnosis of toxicosis by cholinesterase-inhibitor agents like organophosphates and carbamates. In animals, butyrylcholinesterase concentrations have been shown to vary depending on numerous factors such as age, sex, diet, and season of sampling. To establish reference values of plasma butyrylcholinesterase concentrations in common psittacine species, plasma butyrylcholinesterase concentrations were measured in 1942 companion psittacine birds. The birds were classified by age, sex, season, health status, and the presence of feather-damaging behavior. A significant difference was observed among species, with eclectus parrots (Eclectus roratus) having the lowest and African grey parrots (Psittacus erithacus) having the highest reference values. Plasma butyrylcholinesterase concentrations varied by age, health status, and season but not by sex. Concentrations were significantly higher during autumn and spring than during winter and summer, and significantly lower in healthy birds than in sick birds. No significant association between butyrylcholinesterase concentrations and feather-damaging behavior could be established except in lovebirds (Agapornis species). Further research is needed to better understand the effect of nutritional and hormonal factors on butyrylcholinesterase concentrations in psittacine birds and its possible effect on bird cognition.

Key words: butyrylcholinesterase, organophosphate, carbamate, psittacine bird, featherdestructive behavior, avian

Introduction

Butyrylcholinesterase is a glycoprotein enzyme found in plasma and in various compartments within the body and is widely distributed in the nervous system. (1) However, its physiologic role is not well defined. (1) In animals, butyrylcholinesterase concentrations have been shown to vary depending on numerous factors, including age, (2-4) sex, (5-8) diet, (9) and season of sampling. (10-12) A correlation between plasma butyrylcholinesterase and brain acetylcholinesterase levels has been established in some avian (13,14) and reptilian (15) species. Plasma butyrylcholinesterase usually is inhibited more rapidly and to a larger degree than brain acetylcholinesterase and may be scavenging the active forms of cholinesterase-inhibitor compounds that otherwise might inhibit brain acetylcholinesterase activity. (1) Butyrylcholinesterase, also called pseudocholinesterase, has drawn growing interest in human medicine and is used as a target in Alzheimer's disease (16,17) and Parkinson disease treatment. (18) In human medicine, butyrylcholinesterase activity has been shown to increase progressively in patients with Alzheimer's disease, leading to cholinergic deficit, which is considered to contribute to cognitive and behavioral declines. (16,17) Acetylcholinesterase predominates in the healthy human brain, with butyrylcholinesterase considered to play a minor role in regulating brain acetylcholine levels. (16) However, butyrylcholinesterase activity progressively increases in patients with Alzheimer's disease, while acetylcholinesterase activity remains unchanged or declines. (16) Both enzymes are used as therapeutic targets (19) for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral, and global functioning characteristic of Alzheimer's disease. (16) In human medicine, patients with obsessive-compulsive disorders have been shown to have higher serum butyrylcholinesterase concentration, (20) and a correlation between anxiety and serum cholinesterase concentration has been demonstrated. (20,21) Additionally, rats with forebrain cholinergic depletion administered donepezil, an acetylcholinesterase inhibitor used in Alzheimer's disease treatment, (19) showed decreased compulsive behaviors as a result of the treatment. (22) Whether this effect is applicable to birds with feather-destructive behavior has not been evaluated.

In psittacine birds, feather-damaging behavior is a very common reason of presentation to veterinarians, with one study estimating that up to 10% of captive psittacine birds exhibit this abnormal behavior. (23) Feather-damaging behavior is thought to have a medical or psychogenic primary etiology. (24) Several theories have been postulated about the motivational systems that induce feather-damaging behavior, such as redirected foraging or excessive grooming associated with chronic stress. (25) Adrenocorticotropic hormone, opiate, (26) dopaminergic, and serotoninergic systems (27) have been shown to influence the onset, development, and maintenance of feather-damaging behavior. (25) Neurotransmitter deficiencies have been proposed but not confirmed in birds presenting with feather-destructive behavior. This theory is based on results of therapeutic trials, sometimes nonblinded (27) and including a limited number of birds, (26) that showed response to treatment with antidepressants such as clomipramine, (27,28) acting as serotonin and norepinephrine reuptake inhibitors with antidopaminergic effects; selective serotonin reuptake inhibitors such as fluoxetine (29); antidopaminergic antipsychotic drugs such as haloperidol (30,31); or opioid inhibitors such as naltrexone. (25-27,31,32) However, which neurotransmitters actually affect feather-destructive behavior in psittacine birds is unknown. (25) Many of these drugs have a general effect on all behaviors, potentially masking the clinical signs rather than treating them. (25) Differences in neurotransmitter levels and distribution have been found between high and low feather-pecking lines of laying hens, suggesting a strong genetic predisposition. (25) Specific loci have been linked to feather-damaging behavior in poultry, (24,33,34) and selection has proved to be successful in decreasing individual predisposition to this behavior, (35) although environmental factors also have an effect. (25) In psittacine birds, whether a genetic predisposition to feather-destructive behavior exists is unknown, although some species, such as African grey parrots (Psittacus erithacus) seem to be overrepresented, (25) and heritability of the problem has been suspected in Amazon parrots (Amazona species). (22) Comparative research in psittacine birds and humans have been advocated to investigate cognitive and behavioral disorders-in particular, feather-damaging behavior. (25) Therefore, to investigate whether cognitive disorders associated with butyrylcholinesterase as it exists in humans and rats may apply to birds, one aim of this study was to explore a possible association between enzyme concentrations and feather-destructive behavior in psittacine birds.

Butyrylcholinesterase concentrations have been monitored in wild animal species to determine the effect of cholinesterase-inhibitor pesticides. Throughout the world, organophosphates and carbamates are used to control insects in the agricultural industry, in domestic applications such as home gardening and landscape maintenance, and in veterinary medicine for parasite control on livestock. (36) Their application is often relatively localized, and they are short-lived in the environment; thus, they have a low potential for bioaccumulation but a high potential for acute toxicity. (36) Based on median lethal dose values for these chemicals, birds are 10%-20% more susceptible to the toxic effects of cholinesterase-inhibiting compounds than mammals. (36,37) Between 1980 and 2000, the Geographic National Health Center recorded 335 group mortality events involving 8877 birds belonging to 103 avian species, mainly Falconiformes, Anseriformes, (38) Strigiformes, Passeriformes, and Gaviiformes. (39) The primary toxic effect of organophosphate and carbamate pesticides on animals is the phosphorylation of the enzyme acetylcholinesterase and of other esterases at the nerve synapse 40 Phosphorylation inactivates the enzymes and prevents regulation of the level of the neurotransmitter acetylcholine at the synapse, resulting in excessive stimulation of the target organs. (40) Toxic effects include hyperstimulation of muscarinic cholinergic synapses of the heart, airways, digestive tract, and central nervous system, resulting in bradycardia progressing to asystole, bronchoconstriction, increased respiratory and salivary secretions, crop and gastrointestinal stasis, regurgitation, ataxia, seizure, lethargy, and protrusion of the nictitans. (40) This is followed by hyperstimulation of nicotinic cholinergic synapses, associated with paralysis of skeletal muscles, including voluntary respiratory muscles. (37) The affected bird is usually recumbent with clenched feet. Death results from cardiorespiratory effects (37) associated with increased pulmonary secretion in conjunction with respiratory failure. (40) In addition to acute toxicity, anticholinesterase pesticides have been reported to cause sublethal effects such as alteration of thermoregulation, behavior, and reproduction. (39)

Blood levels of butyrylcholinesterase have been measured in a large array of wild species as nondestructive biomarkers of environmental organophosphate exposure, (41) especially in cases of mass mortality in avian populations, such as those involving sandhill cranes (Grus canadensis) in Georgia and West Virginia. (42) In 1988, 5 separate incidences of wild bird mortality were associated with famphur, an organophosphate. (42) All birds showed brain cholinesterase inhibition greater than 50%, which is diagnostic of death associated with cholinesterase-inhibitor toxicosis. (42) Additionally, corn soaked in famphur was retrieved from their gastrointestinal content. (42) A diagnosis of organophosphate or carbamate toxicosis is difficult to confirm in wild psittacine species because of the lack of published data on normal plasma and cerebral cholinesterase levels, except in Hispaniolan Amazon parrots (Amazona ventralis) and because of inconsistency in testing methodology. (40) To our knowledge, plasma butyrylcholinesterase concentrations have not been established in psittacine birds. Reference values of plasma butyrylcholinesterase concentrations determined in pet psittacine species could be applied to their free-living counterparts. In cases of exposure to organophosphates or carbamates, a decreased concentration of butyrylcholinesterase, would be expected, contrary to what is observed in humans with compulsive disorders.

The aims of this study were 3-fold: first, to determine reference values for plasma concentrations of butyrylcholinesterase in psittacine birds and species-specific differences; second, to study the effect of age, sex, and season on butyrylcholinesterase concentrations; and third, to determine whether butyrylcholinesterase concentrations differed in birds presented for feather-damaging behavior compared with healthy birds. Our hypotheses were that species, sex, age, and season would have a significant effect on plasma butyrylcholinesterase values and that birds presented with feather-damaging behavior would have higher values than those in healthy birds.

Materials and Methods

Study population

Psittacine birds presented for clinical examinations between 2002 and 2011 were used for the study. The study population totaled 1942 psittacine birds belonging to 17 subfamilies, 29 genera, and 78 species. The birds were classified as male, female, or unknown based on sexual dimorphism of the species (eg, eclectus parrots [Eclectus roratus]), history of egg laying, or information available from DNA testing or coelomic endoscopy. The birds were classified as fledgling (less than 4 months), juvenile (between 4 months and 2 years), and adult (older than 2 years). Birds were classified as either healthy or nonhealthy based on physical examination results, blood test results, or presenting problems. Birds in the healthy control group (n = 1147) were those that presented for wellness examination and were considered healthy on the basis of the results of physical examination and diagnostic testing. In healthy birds, plasma biochemical results were within reference ranges for the species, (43) and results of any additional tests requested by the owner, including tests for psittacine circovirus. Chlamydia species, or polyomavirus, were negative. Birds in the nonhealthy group (n = 795) were defined as those birds having abnormal findings on physical examination (anorexia, regurgitation, diarrhea, infection of any body system, wound, orthopedic problem) or abnormal blood test results and included birds with evidence of feather-damaging behavior (n = 180). Birds with feather-damaging behavior were defined as birds with damaged or plucked feathers and observed by their owner to remove their feathers, with or without self-mutilation. The suspected cause of the feather-destructive behavior could be either medical (dermatitis, local pain) or psychogenic.

The birds were grouped by subfamilies (n = 17). Only the 8 subfamilies with more than 30 individuals were analyzed, with a total of 1942 birds, including 1147 healthy birds. Sex and age distribution of psittacine birds sampled in this study are indicated in Table 1. The Amazon parrot group comprised the following species: blue-cheeked parrot (Amazona dufresniana), Cuban Amazon (Amazona leucocephald), festive parrot (Amazona festiva), Hispaniolan parrot, lilac-crowned parrot (Amazona finschi), mealy parrot (Amazona farinosa), orange-winged parrot (Amazona amazonica), red-crowned Amazon (Amazona viridigenalis), red-lored parrot (Amazona autumnalis), Tucuman parrot (Amazona tucumana), white-fronted parrot (Amazona albifrons), yellow-crowned parrot (Amazona ochrocephala), yellow-headed parrot (Amazona oratrix), and yellow-naped parrot (Amazona auropalliata). The cockatoo group comprised the following species: blue-eyed cockatoo (Cacatua ophthalmica), Ducorps's cockatoo (Cacatua ducorpsii), galah (Eolophus roseicapilla), little corella (Cacatua sanguined), Moluccan cockatoo (Cacatua moluccensis), pink cockatoo (Cacatua leadbeateri), sulphur-crested cockatoo (Cacatua galerita), Tanimbar cockatoo (Cacatua goffini), white cockatoo (Cacatua alba), and yellow-crested cockatoo (Cacatua sulphured). The lovebirds group comprised the following species: black-cheeked lovebird (Agapornis nigrigenis), Fischer's lovebird (Agapornis fischeri), rosyfaced lovebird (Agapornis roseicollis), and yellow-collared lovebird (Agapornis personata). The group of the macaws included the following species: blue-and-gold macaw (Ara ararauna), blue-throated macaw (Ara glaucogularis), blue-winged macaw (Ara maracana), hyacinth macaw (Anodorhynchus hyacinthinus), military macaw (Ara militaris), red-and-green macaw (Ara chloropterus), red-fronted macaw (Ara rubrogenys), red-shouldered macaw (Ara nobilis), and scarlet macaw (Ara macao). The Poicephalus group included the following species: brown-necked parrot (Poicephalus robustus), Meyer's parrot (Poicephalus meyeri), red-fronted parrot (Poicephalus gulielmi), and Senegal parrot (Poicephalus senegalus).

Blood sample collection and analysis

For blood sample collection, the birds were fasted for 3 hours and then anesthetized with isoflurane administered by face mask. The samples were classified based on the season they were collected as summer, autumn, winter, and spring samples. Blood samples were collected from the right jugular vein with a 1- to 3-mL syringe and 23- to 25-gauge needle. The total amount of blood collected was less than 1% of total body weight in each bird. The blood was collected into a lithium heparin tube and centrifuged at 3111g for 5 minutes. Plasma was separated and stored refrigerated for a maximum of 2 hours during transportation to a veterinary laboratory (Idexx Alfort, 94140 Alfortville, France). The plasma sample was submitted for biochemical analysis (MODULAR P analyzer, Roche, CFI-4070 Basel, Switzerland) as well as for butyrylcholinesterase concentration by colorimetric method between 404 and 415 nm (Roche/Hitachi 912/917/ModularP:ACN510, F. Hoffmann-La Roche Ltd, CFI-4070 Basel, Switzerland) as described elsewhere. (44) None of the birds were in contact with pesticides before presentation according to the medical history.

Statistical analysis

Stata/IC 12.1 (StataCorp LP, College Station, TX, USA) and MedCalc (MedCalc software, Ostend, Belgium) software were used for statistical analysis. The median, mean, 95% confidence interval, standard deviation, minimum, and maximum values of butyrylcholinesterase were determined for each subfamily. Reference intervals of butyrylcholinesterase were determined by using a robust method for small sample sizes (MedCalc). A Kruskal-Wallis rank test followed (when significant) by pairwise Mann-Whitney tests with a Bonferroni-Holm multiple comparison adjustment was used to analyze plasma butyrylcholinesterase concentrations across levels of categorical data, including subfamilies, sex, age, season, and feather-damaging behavior. A Pearson [chi square] test was used to analyze associations between categorical data, including the distribution of sex and age by subfamily group. Statistical significance was set at P < .05.

Results

Means, 95% confidence intervals, standard deviations, medians, and minimum and maximum values of butyrylcholinesterase are summarized in Table 2. Plasma butyrylcholinesterase concentrations differed significantly between subfamily groups (P < .001; Table 2; Fig 1). Butyrylcholinesterase plasma concentrations were significantly lower in eclectus parrots and lovebirds than in cockatiels (Nymphicus hollandicus) and cockatoos (P < .001), and concentrations were significantly lower in eclectus parrots than in lovebirds (P = .007). Macaws and Amazon parrots showed significantly higher plasma butyrylcholinesterase concentrations than cockatiels and cockatoos (P < .001). Butyrylcholinesterase levels were significantly higher in Poicephalus species than in eclectus parrots, lovebirds, cockatiels, cockatoos, macaws, and Amazon parrots (P < .001 for all tests) and significantly lower than in African grey parrots (P < .001).

[FIGURE 1 OMITTED]

Sex was known for only 32% of the birds (329 females and 284 males); in most birds, the sex was undetermined. Butyrylcholinesterase plasma levels did not differ significantly between sex among groups in any class of healthy birds.

Plasma butyrylcholinesterase concentrations differed significantly between fledgling, juvenile, and adult psittacine birds (P < .001), with birds between 4 months and 2 years old having the highest concentrations and birds older than 2 years and fledglings less than 4 months old having the lowest (P < .001). Age distribution was not homogeneous among subfamilies (P < .001), with a higher frequency of adult birds in small species such as lovebirds and cockatiels. However, in birds older than 2 years, butyrylcholinesterase concentrations differed significantly among subfamilies (P < .001).

Butyrylcholinesterase concentrations varied significantly by season (P < .001). Values were significantly higher during autumn and spring than during winter and summer. The number of blood samples collected throughout the year was uniform in all groups except for Poicephalus species, in which more blood samples were collected during the spring. Such weighted sampling could have resulted in an artifactually higher median butyrylcholinesterase concentration in this group.

Plasma butyrylcholinesterase concentrations were significantly lower in healthy birds than in nonhealthy birds (P < .001). Among the 1942 birds, 180 birds presented with feather-damaging behavior. Of these birds, 36 were females, 23 were males, and sex was unknown in the remaining 121 birds. African grey parrots, lovebirds, and cockatoos represented 44%, 17%, and 15%, respectively, of the birds presented with feather-damaging behavior in this population of pet birds (Table 3). However, African grey parrots were the most common species seen, and birds presented with feather-damaging behavior represented 12% of African grey parrots. No significant difference was found in the butyrylcholinesterase concentrations between healthy birds and birds presenting for feather-damaging behavior, except in lovebirds (P = .02). The mean butyrylcholinesterase concentration was 0.17 kU/L in lovebirds with feather-damaging behavior compared with 0.39 kU/L in healthy lovebirds.

Discussion

This study was conducted to establish reference values of butyrylcholinesterase concentrations in captive psittacine birds. The ultimate goal is to apply reference values to their wild counterparts to evaluate exposure of free-living psittacine birds to carbamate and organophosphate pesticides. Additionally, factors associated with variation of butyrylcholinesterase concentrations were evaluated, including species. Values varied significantly among psittacine species, with African grey parrots having the highest values and lovebirds and eclectus parrots the lowest values. Butyrylcholinesterase concentrations did not differ significantly between male and female psittacine birds. Butyrylcholinesterase also showed variation associated with age and season.

In this study, butyrylcholinesterase plasma concentrations observed in psittacine birds ranged between 0.04 and 16.50 kU/L. This was similar to concentrations observed in other species, with plasma concentrations ranging from 0.27 to 3.99 kU/L in European raptor species (45) and from 0.69 to 4.85 kU/L in northern bobwhites (Colinus virginianus) and passerine birds. (10) In Amazon parrots, the reference interval in our study was 0.78-6.18 kU/L. Acetylcholinesterase and butyrylcholinesterase reference ranges have been described in Hispaniolan Amazon parrots, measured by using a modified Michel method and a modified Ellmann spectrophotometric method. (40) Concentrations of butyrylcholinesterase ranged from 0.12 to 0.94 kU/L (with kU/L = mmol/mL per minute because 1 kat = 1 mol/s and 1 U/L= 1 mkat/60 L) in Hispaniolan Amazon parrots. (40) The higher and wider reference interval found in our study may be due to the inclusion of 15 species of Amazon parrots in this group, while excluding Hispaniolan Amazons that may have lower butyrylcholinesterase values than other Amazon parrots. (40) Finally, the different analytic method used in the 2 studies may be responsible for the different results. Establishment of reference values for each psittacine species would likely be more accurate, and a single species was studied when the number of individual birds was greater than 20 (ie, for eclectus parrots, cockatiels, and African grey parrots). However reference values obtained in psittacine birds in this study could still be used as baseline values in evaluating the effect of cholinesterase-inhibiting insect repellents used in outdoor aviaries or in free-ranging birds in areas where pesticides are used, like crop fields. (2) Additionally, reference values for brain cholinesterase levels in psittacine birds would also be useful for postmortem diagnosis, although this was beyond the scope of our study.

One major difference between organophosphate compounds and carbamates is that organophosphates bind irreversibly to acetylcholinesterase, whereas carbamates may separate from their substrate via hydrolytic removal, allowing for reactivation of the enzyme. (37) Antidotes against acetylcholinesterase-inhibitor agents include atropine and pralidoxime. (37) Atropine is a competitive muscarinic receptor antagonist that reverses the actions of acetylcholine on the heart, the airways, and the digestive tract. More specifically, it decreases respiratory secretions and gastrointestinal motility. (37) Atropine is not effective at nicotinic cholinergic receptor sites and thus will not mitigate skeletal muscle paralysis induced by toxic cholinesterase inhibitors. (37) Pralidoxime iodide is an antidote for organophosphate poisoning in mammals but has shown mixed results in raptors. (37) It is contraindicated in cases of carbamate toxicosis because it further inhibits acetylcholinesterase activity. (37) Therefore, it should not be used if the source of toxicosis is unknown. (37) To differentiate organophosphate from carbamate toxicosis, samples with a low level of butyrylcholinesterase activity measured by the modified Ellman spectrophotometric method can be reanalyzed after incubation for 1 to 5 hours at room temperature. If the activity increases, carbamate exposure, rather than organophosphate exposure, is suspected, since the toxicity is reversible. (40)

Butyrylcholinesterase plasma concentrations were shown to vary significantly among psittacine species, with African grey parrots showing the highest values and lovebirds and eclectus parrots the lowest values. Contrary to previous findings in a study evaluating 729 European raptors of 20 species, (45) the interspecies analysis did not show a negative correlation between body mass and cholinesterase activity. For instance, lovebirds were shown to have lower median levels of butyrylcholinesterase (median of 0.26 kU/L) than macaws (median of 2.89 kU/L). Inter-specific differences could also be attributed to phylogenic factors, as has been previously suggested in birds of prey. (45) Australian native species, including cockatiels, cockatoos, and eclectus parrots, showed lower levels of butyrylcholinesterase than Amazon parrots and macaws originating from South America. Among Australian psittacine birds, eclectus parrots had significantly lower levels of plasma butyrylcholinesterase. This finding is in accordance with a previous study, which showed that eclectus parrots and Cacatuini are phylogenically distantly related. (46)

The association between feather-damaging behavior and blood parameters is likely complex because this problem is multifactorial, and causes may also vary among psittacine species. Etiology of feather-damaging behavior has been classified as either psychogenic or medical. (31) However, in most cases, distinction between these two categories is difficult: dermatitis and infection by bacteria and fungi can be a secondary problem of self-mutilation or a primary cause of feather-destructive behavior. Often the practitioner treats medical problems before addressing possible psychogenic disorders. Additionally, primary localized pain or pruritus (such as poor wing trimming, ectoparasites, or allergic dermatitis) (25) could lead to secondary psychogenic feather-damaging behavior, which has been considered a stereotypic behavior. (32) Stereotypic behaviors are defined as repetitive behaviors performed out of their original context that serve no obvious purpose but are elicited by a certain environment. (32,47) Feather removal elicits release of endorphin hormones, (32,48) which could act as a positive reinforcement, leading to a vicious circle similar to trichotillomania in humans. (25,32,49) Complex behavioral mechanisms and medical complications or primary causes are often combined, so feather-destructive behavior has been termed a "syndrome" more than a homogeneous disease. (32) In some psittacine species, idiopathic mutilation syndromes have been described, such as chronic ulcerative dermatitis in lovebirds, self-mutilation in cockatoos, or mutilation syndrome in monk parakeets (Myiopsitta monachus). (32) Therefore, it is likely that birds included in the feather-damaging group in this study actually overlap a variety of disorders. However, this group was created to compare butyrylcholinesterase levels between healthy birds and birds with feather-destructive behavior. The reason for the higher butyrylcholinesterase values observed in African grey parrots in this study is unknown. African grey parrots are known to be prone to develop feather-destructive behavior more frequently because of primary behavioral disorders rather than inflammatory skin disease. (25,49) In humans, butyrylcholinesterase activity progressively increases in patients with Alzheimer's disease, leading to a cholinergic deficits considered to be responsible for the decline in cognitive, behavioral, and global functioning. (16,17) Similarly in humans, patients with compulsive behaviors have been shown to have higher butyrylcholinesterase concentrations. (20) Whether or not this increase in enzyme levels might predispose African grey parrots to cognitive impairments remains to be determined, but it appears unlikely because Poicephalus species also showed high levels of butyrylcholinesterase and are not prone to feather-damaging behavior.

In this population, butyrylcholinesterase activity was not significantly different in birds presenting with feather-damaging behavior and healthy birds, except in lovebirds, with healthy lovebirds showing a higher level of butyrylcholinesterase than lovebirds with feather-damaging behavior. In this species, feather-damaging behavior is typically associated with an underlying medical problem, (50) which possibly could affect butyrylcholinesterase concentrations, whereas primary behavioral causes have been reported more commonly in other species, such as cockatoos and African grey parrots. (50) Of note, nonhealthy birds had higher butyrylcholinesterase concentrations than healthy birds (P < .001), whereas feather-damaging lovebirds had lower butyrylcholinesterase concentrations than healthy lovebirds. Which disease processes affect butyrylcholinesterase concentrations in nonhealthy birds is unknown, because this group was heterogeneous. Possibly, only certain diseases affected this parameter, but overall, butyrylcholinesterase concentrations were significantly higher in nonhealthy psittacine birds than in healthy psittacine birds. Additionally, all environmental parameters could not be controlled in this retrospective study, some of which could have been different in the group of healthy birds compared with nonhealthy birds. Ideally, a prospective study would be necessary to evaluate the effect of a given disease on butyrylcholinesterase concentrations. However, it is still worth noting that some nonhealthy birds may have significantly elevated butyrylcholinesterase plasma concentrations, similar to those observed in humans. (13,14)

Sex-related differences affecting butyrylcholinesterase concentrations have been previously reported in little owls (Athene noctua) but not in other European raptors. (45) Male northern cardinals (Cardinalis cardinalis) (7) and Japanese quail (Coturnix japonica) (8) have higher values of cholinesterase 1, another plasma esterase, than their female counterparts. No significant association with sex could be demonstrated in our study. However, this could be a result of the low number of sexed birds included in the sampled population.

Age-related differences affecting butyrylcholinesterase levels have been previously reported in sparrowhawks (Accipiter nisus), European kestrels (Falco tinnunculus), tawny owls (Strix aluco), (45) eastern bluebirds (Sialia sialis), and European starlings (Sturnus vulgaris),' with adults having higher levels than juveniles in altricial species. Conversely, among precocial species, plasma butyrylcholinesterase levels have different trends. In mallard ducks (Anas platyrhynchos) and domestic chickens, concentrations decline as the bird ages. (51,52) In this study, juvenile psittacine birds between 4 months old and 2 years old had the highest butyrylcholinesterase concentrations, whereas the concentration decreased significantly in adults. This observation is the opposite of what has been previously reported in other avian altricial species. The definition of juvenile as a bird older than 4 months old used in this study was arbitrary and does not apply to all psittacine species. Unfortunately, the hatch date of every bird was not available in this study population, and continuous data for age would have been preferred. A more accurate analysis of the association of age on butyrylcholinesterase concentrations in psittacine birds would be warranted.

Seasonal trends in butyrylcholinesterase activity have been previously observed in captive female northern bobwhite, with significantly lower activity during summer and fall than during the rest of the year. (10) The reason for this activity trend was not elucidated, but a hormonal cause was suspected. (53) No seasonal trend could be detected in European raptors (45) or in American passerines. (10) In psittacine birds, values were significantly higher during autumn and spring than during winter and summer. The reason for this seasonal trend in our study remains undetermined.

Dietary factors were not investigated in this study. Most of the privately owned birds in the current study were fed pellets or seeds, nuts, greens, and fruits. However, a thorough evaluation of the quantity and quality of the food provided by owners was not possible. Plasma butyrylcholinesterase activity can be influenced by the diet because of its hepatic synthesis. (1) In malnourished humans, plasma values have been shown to decrease. (54) A decrease of butyrylcholinesterase effect has also been experimentally induced in rats supplemented with fish oil instead of coconut, olive, or corn oil. (9) Therefore, a bias associated with different diets among species cannot be ruled out in our study.

The results of this study provided reference values of butyrylcholinesterase plasma concentrations for common psittacine species and showed a significant difference among species. No association between this enzyme and feather-damaging behavior could be established except in lovebirds. No association with sex was found. Butyrylcholinesterase concentrations showed variation associated with age and season, with significantly higher concentrations during autumn and spring than during winter and summer and significantly lower values in healthy birds than in sick birds. Further research is needed to better understand the effect of nutritional and hormonal factors on butyrylcholinesterase levels in psittacine birds and its possible effect on bird cognition.

Acknowledgments: We thank Jacques Turet and Julien Vergneau for their help in data analysis.

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Claire Grosset, DVM, IPSAV, Christian Bougerol, DVM, Philip H. Kass, DVM, PhD, Dipl ACVPM, and David Sanchez-Migallon Guzman, LV, MS, Dipl ECZM (Avian), Dipl ACZM

From the William R. Pritchard Veterinary Medical Teaching Hospital (Grosset), the Departments of Medicine and Epidemiology (Guzman), and Population Health and Reproduction (Kass), School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA; and the Veterinary Clinic, 50 rue Molitor, 75016 Paris, France (Bougerol).
Table 1. The species groups, sex, and age of psittacine birds (N =
1942) sampled for plasma butyrylcholinesterase levels.

Group                   n                   Sex

                              Unknown sex   Female   Male

African grey parrots   639        452        103      84
Amazon parrots         325        224         55      46
Cockatiels             174        134         25      15
Cockatoos              315        221         40      54
Eclectus parrots        35          7         17      11
Lovebirds              122         90         17      15
Macaws                 165         99         38      28
Poicephalus species    167        102         34      31
Total                  1942      1329        329     284

Group                              Age

                       <4 mo   4 mo to 2 y   >2 y

African grey parrots     5         218        416
Amazon parrots           0          90        235
Cockatiels               0          19        155
Cockatoos                4         122        189
Eclectus parrots         0          14         21
Lovebirds                1           6        115
Macaws                   6          93         66
Poicephalus species     11         107         49
Total                   27         669       1246

Table 2. Butyrylcholinesterase plasma concentrations (expressed in kU/
L = mmol/mL per minute) in healthy psittacine birds (n = 1147).
Reference ranges are based on a robust 95% confidence interval.

Group (a)                n     Median   Reference range   Mean     SD

African grey parrot A   351     6.59      0.71-12.45      6.65    2.98
Amazon parrots B        205     3.49      0.78-6.18       3.50    1.36
Cockatiels C             65     1.82      0.45-3.20       1.91    0.68
Cockatoos C             228     1.80    0-5.23            2.15    1.74
Eclectus parrots D       22     0.14      0.02-0.25       0.14    0.05
Lovebirds E              31     0.26    0-1.41            0.39    0.57
Macaws B                120     2.89    0-6.21            3.21    1.55
Poicephalus species F   125     4.70      1.19-8.29       4.82    1.78

Group (a)               Min     Max

African grey parrot A   0.06     14.6
Amazon parrots B        0.24     6.94
Cockatiels C            0.70     4.05
Cockatoos C             0.27    17.20
Eclectus parrots D      0.31     0.24
Lovebirds E             0.01     2.82
Macaws B                0.01      7.2
Poicephalus species F   0.90    10.24

(a) Means with different letters are significantly different.

Table 3. Number and distribution by species of total birds (N = 1942),
healthy birds (n = 1147), and nonhealthy birds with feather-damaging
behavior (FDB; n = 180) included in the study of butyrylcholinesterase
plasma concentrations in psittacine birds. All birds with FDB were
part of the total nonhealthy bird group (n = 795).

Group                     Total birds            Healthy birds
                       (% total with FDB)   (% total healthy group)

African grey parrots         639 (12)               351 (30)
Amazon parrots               325 (4)                205 (18)
Cockatiels                   174 (6)                 65 (6)
Cockatoos                    315 (9)                228 (20)
Eclectus parrots              35 (14)                22 (2)
Lovebirds                    122 (25)                31 (3)
Macaws                       165 (5)                120 (10)
Poicephalus species          167 (2)                125 (11)
Total                       1942 (9)               1147 (100)

Group                    Birds with FDB
                       (% total FDB group)

African grey parrots         79 (44)
Amazon parrots               13 (7)
Cockatiels                   11 (6)
Cockatoos                    27 (15)
Eclectus parrots              5 (3)
Lovebirds                    31 (17)
Macaws                        9 (5)
Poicephalus species           5 (3)
Total                       180 (100)
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Title Annotation:Original Studies
Author:Grosset, Claire; Bougerol, Christian; Kass, Philip H.; Guzman, David Sanchez-Migallon
Publication:Journal of Avian Medicine and Surgery
Article Type:Report
Date:Mar 1, 2014
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