Associations Between Platelet Monoamine Oxidase-B Activity and Acquired Colour Vision Loss in a Fish-Eating Population

Neurotoxicology and Teratology 28 (2006) 446–452 www.elsevier.com/locate/neutera

Associations between platelet monoamine oxidase-B activity and acquired colour vision loss in a fish-eating population

Christopher John Stamler a,1, Donna Mergler b, Nadia Abdelouahab b, ⁎ Claire Vanier b, Hing Man Chan a,

a Centre for Indigenous Peoples' Nutrition and Environment and School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC, Canada H9X 3V9 b Centre des interactions entre la sante et l'environnement (CINBIOSE), Universite du Quebec a Montreal, C.P. 8888, Succ. Centre-ville, Montreal, QC, Canada H3P 3P8 Received 23 February 2006; received in revised form 13 May 2006; accepted 13 May 2006 Available online 20 May 2006

Abstract

Platelet monoamine oxidase-B (MAO-B) has been considered a surrogate biochemical marker of neurotoxicity, as it may reflect changes in the monoaminergic system in the brain. Colour vision discrimination, in part a dopamine dependent process, has been used to identify early neurological effects of some environmental and industrial neurotoxicants. The objective of this cross-sectional study was to explore the relationship between platelet MAO-B activity and acquired colour discrimination capacity in fish-consumers from the St. Lawrence River region of Canada. Assessment of acquired dyschromatopsia was determined using the Lanthony D-15 desaturated panel test. Participants classified with dyschromatopsia (n=81) had significantly lower MAO-B activity when compared to those with normal colour vision (n=32) (26.5±9.6 versus 31.0±9.9 nmol/min/20 μg, P=0.030)). Similarly, Bowman's Colour Confusion Index (CCI) was inversely correlated with MAO-B activity when the vision test was performed with the worst eye only (r=−0.245, P=0.009), the best eye only (r=−0.188, P=0.048) and with both eyes together (r=−0.309, P=0.001). Associations remained significant after adjustment for age and gender when both eyes (P=0.003) and the worst eye (P=0.045) were tested. Adjustment for heavy smoking weakened the association between MAO-B and CCI in the worst eye (P=0.140), but did not alter this association for both eyes (P=0.006). Adjustment for blood-mercury concentrations did not change the association. This study suggests a relationship between reduced MAO-B activity and acquired colour vision loss and both are associated with tobacco smoking. Therefore, results show that platelet MAO-B may be used as a surrogate biochemical marker of acquired colour vision loss. © 2006 Elsevier Inc. All rights reserved.

Keywords: Surrogate biomarker; Monoamine oxidase; Colour vision; Cigarette smoking; Mercury

1. Introduction are two isoenzymes, MAO-A and MAO-B, which differ in substrate and inhibitor specificity [32,49]. Both isoenzymes are Monoamine oxidase (MAO, EC 1.4.3.4) is a flavo-enzyme distributed throughout the central nervous system (CNS) as well bound to the outer membrane of mitochondria and is involved in as non-neuronal peripheral tissue [54]. the oxidative inactivation of monoamine neurotransmitters The measurement of MAO-B activity in non-neuronal including dopamine, serotonin and noradrenaline [49]. There blood platelets has been proposed as a marker for aberrations of the monoaminergic nervous system [45]. Both genetic and environmental factors are known to cause variations in MAO ⁎ Corresponding author. Current address: Community Health Program, activity levels, which have been linked with personality University of Northern British Columbia, 3333 University Way, Prince George, disorders and some neurological diseases [20,45]. More BC, Canada V2N 4Z9. Tel.: +1 250 960 5237; fax: +1 250 960 5744. E-mail address: [email protected] (H.M. Chan). recently, platelet MAO-B has been investigated for its use as 1 Current address: Community Health Program, University of Northern a biochemical marker of neurotoxicity for environmental and British Columbia, 3333 University Way, Prince George, BC, Canada V2N 4Z9. occupational contaminants [19,38,52]. Specifically, exposures

0892-0362/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ntt.2006.05.004 C.J. Stamler et al. / Neurotoxicology and Teratology 28 (2006) 446–452 447 to styrene [16], manganese [50], cigarette smoke [3], alcohol 2. Methods [18] and mercury (Hg) [52] have all been associated with reduced platelet MAO-B activity levels in humans. These 2.1. Population and sampling functional modifications in the surrogate platelet tissue are thought to reflect similar MAO activity changes in the CNS This study was conducted as part of the Collaborative [24,25,38]. However, it remains unclear how an observed Mercury Research Network (COMERN) investigation into Hg reduction in platelet MAO-B activity may be associated with exposure and effects on fish-eating communities in Canada. The specific sub-clinical neurofunctional variations. study population lived in the Lake St. Pierre region in the Colour vision discrimination has been used to detect the municipality of Sorel-Tracy (Quebec, Canada). Participants early neurofunctional alterations following exposure to some were recruited through the Lake St. Pierre Fisher's Association, neurotoxic chemicals [28]. The retina is particularly sensitive to radio stations and local newspapers. This cross-sectional study functional damage by toxicants due to the fenestrated nature of was carried out from February to April 2003. Persons were the choriocapillaris [26]. Several neurotoxic compounds excluded from participating if they did not report eating fish including Hg, toluene, styrene, alcohol and tobacco smoke are from the Lake St. Pierre. Also, due to the known effect of age on linked with acquired dyschromatopsia in humans [23,28,40]. colour vision, participants were excluded from analysis if they This acquired loss of colour discrimination is primarily were over 65 years of age. In total, data from 116 subjects were associated with an impairment of the blue-yellow colour axis, used. Informed consent was obtained by the participants and and less frequently with a concomitant loss in the blue-yellow coded questionnaires were completed to determine socio- and red-green axis [30]. The Koellner's rule suggests that colour demographic and lifestyle information. Age, gender, smoking vision loss in the blue-yellow range is associated with habits and vision impairments were collected by questionnaire. impairments in retinal function (cone neural system) and loss Ethical approval to conduct this study was granted by the in the red-green range is associated with optic nerve damage McGill University and the University of Quebec at Montreal [30]. While specific mechanisms of chemical-induced acquired Ethical Review committees. colour vision loss are relatively unknown, it has been suggested that disruption of neurochemical signaling pathways in the 2.2. Blood-Hg measurement retinal cells may be involved [28]. Dopamine is synthesized in the retinal amacrine cells, which Whole blood samples (7 ml) were drawn into heparinized is thought to act on both inner and outer retinal neurons [21,41]. tubes, and analysed for total Hg using cold vapour atomic It has been established that the dopaminergic system is absorption spectrometry. The detection limit was 0.2 μg/l for important for color vision pathways in both laboratory animals blood-Hg analysis. Analysis was carried out at the Centre de and in humans [22,41,47]. Parkinson's disease, a degenerative Toxicology du Quebec. Certified reference material was analyzed disorder affecting dopaminergic neurons in the CNS, disrupts for quality control purposes. colour vision as well as other visual functions [9,46]. Colour vision impairment can be partially restored following the 2.3. Platelet MAO-B measurement administration of L-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine precursor and common treatment of Parkinson's Blood samples were drawn into vacutainer tubes containing disease [10]. Dopamine in the retina is metabolized and EDTA-K2. Blood was centrifuged at 200×g for 10 min to obtain regulated by MAO [44]. While only observed in case studies, platelet-rich plasma (PRP). The PRP was centrifuged at 3000×g overdose and prolonged use of MAO-inhibitor drugs have been for 25 min at 4°C to pellet platelets. Platelets were washed twice linked with retinal and optical neuropathies in humans and suspended in phosphate buffer. The concentration of protein [1,29,31]. Therefore, adequate MAO function may be important in platelets preparations were determined by the Bradford for colour vision and its signaling pathways. method [7] using bovine serum albumin as the standard. We have previously reported that low-level Hg exposure and Platelets were stored at −80°C until biochemical assays were heavy smoking is associated with a reduction in platelet MAO- performed. Storage conditions and stability of the samples have B activity in a fishing community in southern Quebec, Canada been tested and the conditions were optimized [51]. [52]. While these associations indicated a possible biochemical MAO-B activity analysis was based on the method described effect, it is uncertain whether these changes could predict early by Krajl [33]. Platelets (20 μg protein) were mixed in a Triton neurofunctional effects or neurotoxicity. Because both heavy X-100 (0.5%) solution, and then diluted in 3 ml of phosphate smoking and Hg exposure have been associated with acquired buffer saline (50 mM, pH 7.8). Reaction was initiated by the colour vision loss in previous studies [23,35], our objective was addition of a concentration range of the MAO-B substrate, to explore the relationship between platelet MAO-B activity and kynauramine dihydrobromide (1.5–50 μM), followed by a colour vision performance in the same fishing community. 30 min incubation at 37 °C. Following the incubation, the Understanding the interactions between the neurotoxicant, reaction was stopped by the addition of 5 M perchloric acid and biochemical markers and neurofunctional effects may assist in centrifuged at 2000×g for 10 min. The supernatant was diluted the (1) identification of mechanisms of early toxic effects and with 1 M NaOH and the fluorescence was read at 318 nm (2) development of novel biomarkers that can be used for risk excitation and 380 nm emission on a spectrofluorometer. assessment strategies. Product concentration was calculated based on the standard 448 C.J. Stamler et al. / Neurotoxicology and Teratology 28 (2006) 446–452 curve of 4-hydroxyquinoline (0–30 nM) and results were adjusted for gender and age. Pair-wise comparisons were expressed in nanomoles of product formed per minute per 20 μg performed using Bonferroni post-hoc analysis. of platelet protein. Multiple linear regression analyses were also conducted with the CCI values (both, worst and best eye(s)) as the dependent 2.4. Colour discrimination assessment variable and platelet MAO-B activity, gender and age as independent variables. A regression coefficient for MAO-B Lanthony D-15 desaturated colour panel was used to assess activity was determined for each eye tested. Both heavy smoking colour discrimination and dyschromatopsia [34]. Participants (>14 cigarettes/day) and blood-Hg (>3.4 μg/l) were associated were asked to place 15 caps in order of chromatic similarity with reduced platelet MAO-B activity in this human population starting from a fixed reference cap. The test was performed first [52]. In order to determine if these environmental variables can with both eyes together and then with the right and left eye explain the association between MAO-B and colour vision, CCI separately. Colour vision loss was classified within types of scores were subsequently adjusted for heavy smoking and/or acquired dyschromatopsia based on Verriest's classification: type blood-Hg concentrations and regression coefficients for platelet III, a loss in the blue-yellow range; type II, a concomitant loss in MAO-B activity were determined. Changes in MAO-B the blue-yellow range and red-green range; and type I, a loss in regression coefficients and P-values were noted. the red-green range [56]. The response patterns were indicative of either acquired or congenital colour vision loss. Participants 3. Results were classified as dyschromatopic if they had one of the three types of colour vision dysfunction in either the left or right eye. 3.1. Study population description The Colour Confusion Index (CCI) was calculated and used to estimate acquired colour loss as a score on a continuous scale Three participants were classified as being congenitally [6]. A perfect test was given a score of 1.0, while scores greater colour blind and were excluded from analysis. The study group than 1.0 reflect increasingly incorrect placed caps. The scores was composed of 68 men and 45 women, who had an average from the left eye, right eye and both eyes were determined. The age (S.D.) of 49 (13) years. Nineteen participants reported colour vision data were separated into the lowest CCI value smoking more than 14 cigarettes/day and were classified as representing the best score (best eye), and the highest CCI heavy smokers. The average alcohol intake was 161 g/week and representing the worst score (worst eye) [11]. Data from ranged from 0 to 898. Only two participants had reported obtained from both eyes were also used in the analysis. alcohol intake greater than 500 g/week. Average blood-Hg concentration (S.D.) was 2.5 (3.0) μg/l and 28 participants had 2.5. Statistical analysis levels greater than 3.4 μg/l. MAO-B activity was normally distributed and had a mean (S.D.) of 27.6 (9.8) and a median Data from MAO-B kinetic analyses were curve fitted using (range) of 26.6 (5.5–65.4) nmol/min/20 μg. GraphPad Prism (Version 3.02, GraphPad Software Inc., San Four participants reported cataracts and therefore the Diego, CA, USA) to calculate maximum MAO-B velocity affected eye was not tested. Of the participants, 35 were (Vmax). Statistical analysis was conducted using SPSS considered having normal colour vision, while 81 were statistical software, Version 10.0, standard version (SPSS Inc., dyschromatopic. Of those classified as dyschromatopic, 4 Chicago, IL, USA). Continuous data was analyzed for were type I, 24 were type II and 53 were categorized as type normality using the Kolmogorov–Smirnov test. III (Table 1). 60% of the women and 79% of the men were Individuals classified as being congenitally colour blind classified as dyschromatopic. were excluded from all analyses. Differences between platelet MAO-B activity in the dyschromatopic and normal colour 3.2. Confounding factors vision groups were determined using a Student's t-test. Differences among mean MAO-B activity in the normal and Age was positively correlated with CCI values in both specific dyschromatopic category were determined using a one- (r=0.160, P=0.090), the worst (r=0.190, P=0.046) and the way analysis of variance (ANOVA). Simple Pearson correlations were determined to evaluate associations between CCI Table 1 values (best, worst and both eye(s)) and platelet MAO-B Mean platelet MAO-B activity±S.D. (nmol/min/20 μg) in participants classified activity in both women, men and in the total population. by colour vision category Student's t-tests were used to detect difference in CCI values Colour vision Total population Men Women between possible confounding factors; gender, heavy smokers category n MAO-B n MAO-B n MAO-B (y/n), blood-Hg (above/below 3.4 μg/l). Simple correlations were used to evaluate associations between CCI, age and Normal 32 30.9 (9.9) 14 27.5 (8.9) 18 33.6 (9.8) Dyschromatopsia 81 26.5 (9.6) ⁎ 54 25.8 (9.8) 27 27.8 (9.1) ⁎ alcohol consumption. Type I 4 29.0 (9.5) 4 29.0 (9.5) The participants were separated into tertile groups based on Type II 24 26.2 (8.3) 18 26.1 (8.9) 6 26.3 (6.5) platelet MAO-B activity levels, and mean adjusted CCI scores Type III 53 26.5 (10.3) 32 25.3 (10.5) 21 28.3 (9.9) were compared using General Linear Model (GLM) Univariate ⁎ Indicates significant (P≤0.05) difference from normal colour vision group procedure. CCI scores (both, worst and best eye(s)) were as determined using Student's t-test. C.J. Stamler et al. / Neurotoxicology and Teratology 28 (2006) 446–452 449

Table 2 congenitally colour blind participants excluded from analysis Correlations between platelet MAO-B activity and colour confusion index (CCI) had an average platelet MAO-B activity (SD) of 17.9 Eye tested CCI, mean Correlations (r) with platelet MAO-B activity (5.6) nmol/min/20 μg. (S.D.) Total (113) Men (68) Women (45) Simple correlations indicated that platelet MAO-B activity Both eyes a 1.26 (0.27) −0.309⁎⁎⁎ −0.244⁎ −0.329⁎ was negatively associated with CCI for the best (P=0.048), Best eye a 1.30 (0.30) −0.188⁎ −0.133 −0.156 worst (P =0.009) and both (P <0.001)eye(s)(Table 2). Worst eye a 1.48 (0.38) −0.245⁎⁎ −0.173 −0.244 Negative correlations were also observed between MAO-B ⁎P<0.05, ⁎⁎P<0.01, ⁎⁎⁎P<0.001. and CCI when examined separately in men and women, but a CCI for best worst and both eye(s) was log transformed. were significant for both eyes only (Table 2). Multiple regression analyses were conducted to control for best (r=0.253, P=0.007) eye(s) tested. Men had average CCI the effects of confounding variables (Table 3). After adjustment values (S.D.) of 1.30 (0.28), 1.58 (0.41) and 1.38 (0.33) for for age and gender, lower MAO-B activity remained signifi- both, worst and best eye(s), respectively. Women had lower CCI cantly associated with increased acquired colour vision loss values compared to men; both eyes 1.18 (0.23), worst eye 1.32 (increased CCI) as determined with the worst and both eyes, but (0.26) and best eye 1.18 (0.19). Heavy smokers had not the best eye. The inclusion of heavy smoking and/or blood- significantly higher average CCI values (S.D.) in the best eye Hg levels did not substantially affect the relationship between (1.28 (0.28) versus 1.42 (0.35), P=0.050) and worst eye (1.66 MAO-B and CCI score determined when both eyes were used. (0.39) versus 1.44 (0.36), P=0.026) when compared to those However, the association between MAO-B and CCI determined who smoked less than 15 cigarettes/day or were non-smokers. from the worst eye was substantially weakened after adjust- CCI values were higher in heavy smokers when both eyes were ments were made for the effects of heavy smoking. Adjustment used, although the difference was not significant (1.24 (0.27) for blood-Hg concentrations did not change the association versus 1.31 (0.22), P=0.290). While participants with blood-Hg between MAO-B and colour vision. levels above 3.4 μg/l had higher CCI values in both eyes (1.32 In order to further investigate the relationship between (0.28) versus 1.23 (0.26), P=0.107), the worst eye (1.54 (0.37) MAO-B and colour vision, the population was stratified into versus 1.46 (0.38), P=0.342) and the best eye (1.35 (0.32) tertile groups based on enzyme activity, and the mean CCI versus 1.28 (0.29), P=0.281) when compared to the rest of the (adjusted for age and gender) were compared in each group population, these differences were not significant. Alcohol (Fig. 1). Participants in the lowest MAO-B tertile group had the intake did not significantly correlate with CCI values (data not highest mean CCI for all three eye test conditions, although the shown). difference only reached a significant level when both eyes were tested (P=0.030). 3.3. Association between platelet MAO-B activity and colour vision 4. Discussion

Participants classified as dyschromatopic had significantly The major finding from this study is that low platelet MAO- (P=0.030) lower mean platelet MAO-B activity levels when B activity was associated with acquired color vision loss in compared to participants with normal colour vision (Table 1). humans, which can partially be explained by heavy cigarette Although participants with type III (blue/yellow) and type II smoking. This novel finding suggests a continuum of effects (combined blue/yellow and red/green) colour vision displayed relating exposure to a toxicant, to biochemical changes, and to lower MAO-B activity than those with normal colour vision neurofunctional impairment. (Table 1), one-way ANOVA indicated no significant effect (F To our knowledge, an association between MAO-B and (3,112)=1.68, P=0.175). MAO-B activity was also signifi- acquired colour vision loss has not been specifically investi- cantly lower in dyschromatopic women when compared to gated in humans. However, several case reports suggest that use those with normal colour vision (P=0.05). Although not of MAO-inhibitor drugs can result in visual abnormalities and significant, MAO-B was also lower in males with dyschroma- in some cases colour vision impairments [1,29,31].The topsia than those with normal colour vision. The three mechanism of this toxicity has not been examined, but may

Table 3 Regression coefficients (β-value) for platelet MAO-B activity adjusted for confounders (age and gender), smoking and/or blood-Hg levels Colour Adjustment for confounders b Adjustment for confounders b Adjustment for confounders b Adjustment for confounders b, Confusion and heavy smoking and blood-Hg heavy smoking and blood-Hg Index a β -value (S.E.) c P β -value (S.E.) c P β -value (S.E.) c P β -value (S.E.) c P Both eyes −2.39 (0.78) 0.003⁎⁎ −2.30 (0.81) 0.006⁎⁎ −2.30 (0.79) 0.004⁎⁎ −2.15 (0.82) 0.010⁎ Best eye −1.20 (0.84) 0.159 −0.81 (0.87) 0.353 −1.11 (0.85) 0.191 −0.66 (0.88) 0.455 Worst eye −1.95 (0.96) 0.045⁎ −1.47 (0.99) 0.140 −1.85 (0.97) 0.059 −1.27 (1.00) 0.205 a Logarithmically transformed CCI values for best, worst and both eye(s) represent the dependent variables in the multiple linear regression model. b Confounders included gender and age. c β-values (S.E.)×103. 450 C.J. Stamler et al. / Neurotoxicology and Teratology 28 (2006) 446–452

superior colour vision and higher platelet MAO-B activity than men. However, associations between MAO-B and CCI appeared to be independent of gender, as negative correlations were observed separately in both men and women. Multiple linear regression analysis also showed that this association was significant after adjusting for the effects of age and gender, but only when the worst and both eye(s) were used. The relationship between MAO-B and CCI using the best eye was not significant after adjusting for age and gender. It is widely known that acquired dyschromatopsia can be mono-lateral [57], and this may explain why the strength of the associations was dependent on the eye being tested. The monoaminergic system plays an important role in visual processes as the cellular layers of the primary visual cortex are innervated by both serotonergic and noradrenergic neurons [42]. Dopamine and its receptors have been localized to the retina of vertebrates and have been shown to be important for colour vision function [21,22,41]. The mechanism for acquired colour vision loss is thought to occur through either altered cone function or disrupted neurotransmitters systems in the retina [28]. Studies have shown that the injection of a dopamine receptor (D1) antagonist, SKF38393, or a dopaminergic neurotoxin (6-OH- dopamine) into the vitreous of the eye impairs colour vision discrimination in goldfish [41]. Similarly, reduced colour vision perception in Parkinson's disease patients can be reversed following the administration of a dopamine precursor, L-DOPA [10]. This evidence suggests that depletion of dopamine in the CNS is the underlying mechanism of impaired colour vision differentiation in the models examined [22]. However, this simple dopamine depletion mechanism of action does not explain the associations between MAO-B activity and colour vision in the present study, suggesting the possibility of an alternative Fig. 1. Mean (±S.E.) adjusted CCI scores for subjects in platelet MAO-B mechanism. In addition to changes in retinal cells, long-term activity tertile groups (MAO-B range shown brackets). CCI score was adjusted disruption of MAO in other regions of the visual system, for the effects of age and gender and data for both, worst and best eye(s) are including the optic nerve and visual cortex, may be involved in shown. There were 37 or 38 participants per tertile group. Bars with different chemical triggered mechanism of colour vision impairment. letters are significantly different, P<0.05. Cigarette smokers have reduced colour vision when compared to non-smokers [23]. It is difficult to identify the involve impairment of monoaminergic neurotransmitter sys- biochemical mechanism for this interaction due to the numerous tems. Other studies suggest that platelet MAO-B is associated chemicals present in tobacco smoke. However, chemicals from with other aspects of the visual system, including visual illusion tobacco have been identified to reversibly inhibit both rat brain strength [37] and visual evoked potentials [36]. In the present MAO-A and MAO-B function in vitro [12]. Biochemical and study, participants classified as dyschromatopic displayed PET (positron emission tomography) studies similarly indicate significantly lower MAO-B activity, when compared to those that heavy smoking results in MAO reduction in platelets, brain with normal colour vision. The majority of participants with and other peripheral regions in humans [4,24,25]. In the present dyschromatopsia had impairments in the blue-yellow range study, heavy smoking (>14 cigarettes/day) was associated with (n=54), while 25 participants had a combination of red-green approximately a 25% reduction in platelet MAO-B activity [52]. and blue-yellow impairment. The high prevalence of dyschro- When adjustments were made for heavy smoking, the matopsia is most likely due to the age of this cohort, as colour association between MAO-B and CCI was substantially vision is known to decreases with age [27]. Previous reports weakened with the worst eye only. Heavy smoking did not have suggested that platelet MAO-B activity also increases with alter this association when CCI from both eyes was used. The age [8]; however, we did not observe this association [52]. visual cortex plays a key role in analysing and interpreting Simple correlations using the Colour Confusion Index (CCI) colour signals, particularly when both are used simultaneously scores were also associated with MAO-B activity, as partici- [26]. Therefore, it is difficult to interpret these eye-specific pants with lower enzyme levels had increased acquired colour responses given the complexity of colour analysis in the cortex. vision loss. In addition to age, gender is an important Moreover, it is possible that the established monocular nature of confounder that must be addressed. In this study, women had dyschromatopsia may explain some of these differences [57]. C.J. Stamler et al. / Neurotoxicology and Teratology 28 (2006) 446–452 451

While a direct cause–effect relationship can not be established, Technical assistance from M. Durant, A. Pull, J. Fontaine, N. it appears the association between colour vision and platelet Basu, K.M. Loua, L. Rostas, A. Shapiro and D. Leggee was MAO-B can be partially explained by the effects of heavy greatly appreciated. This study was funded by a research grant cigarette smoking. from the Collaborative Mercury Research Network Hg compounds are neurotoxic and exposure to methyl- (COMERN) to D. Mergler and H.M. Chan, and a Discovery mercury (MeHg) is well known to damage the visual cortex Grant from the Natural Science and Engineering Research [53]. Studies performed in adults showed that visual function, Council (NSERC) of Canada to H.M. Chan. C. Stamler was including colour discrimination performance, was impaired by financially supported by COMERN and the NSERC Graduate MeHg from dietary fish consumption [35,39]. Similarly, Student Scholarship. relationships were observed in industrial workers exposed to Hg vapour [14,55], which was shown to be reversible [13]. MeHg is known to inhibit MAO function [15] and we have References recently shown that brainstem MAO activity is reduced following a low-level gestational exposure to MeHg in female [1] M. Ardouin, M. Urvoy, T. Raoul, M.C. Herve, Electroretinographic study of a case of monoamine oxidase inhibitor poisoning, Bull. Soc. Ophtalmol. rats [5]. Given that Hg exposure was also associated with Fr. 67 (1967) 920–924. decreased platelet MAO-B activity in the Lake St. Pierre [2] E. Bergamaschi, A. Smargiassi, A. Mutti, S. Cavazzini, M.V. Vettori, R. population, it is reasonable to suggest that MAO-B may be a Alinovi, I. Franchini, D. Mergler, Peripheral markers of catecholaminergic surrogate biomarker of early neurotoxicity for Hg. 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