Cerebellum cholinergic muscarinic receptor (subtype-2 and -3) and cytoarchitecture after developmental exposure to methylmercury: an immunohistochemical study in rat.
The developing central nervous system (CNS) is a target of the environmental toxicant methylmercury (MeHg), and the cerebellum seems the most susceptible tissue in response to this neurotoxicant. The cholinergic system is essential for brain development, acting as a modulator of neuronal proliferation, migration and differentiation processes; its muscarinic receptors (MRs) play pivotal roles in regulating important basic physiologic functions. By immunohistochemistry, we investigated the effects of perinatal (GD7-PD21) MeHg (0.5 mg/kg bw/day in drinking water) administration on cerebellum of mature (PD36) and immature (PD21) rats, evaluating the: (i) M2- and M3-MR expression; (ii) presence of gliosis; (iii) cytoarchitecture alterations. Regarding to M2-MRs, we showed that: at PD21, MeHg-treated animals did not display any differences compared to controls, while, at PD36 there was a significant increase of M2-immunopositive Bergmann cells in the molecular layer (ML), suggesting a MeHg-related cytotoxic effect. Similarly to M2-MRs, at PD21 the M3-MRs were not affected by MeHg, while, at PD36 a lacking immunoreactivity of the granular layer (IGL) was observed after MeHg treatment. In MeHg-treated rats, at both developmental points, we showed reactive gliosis, e.g. a significant increase in Bergmann glia of the ML and astrocytes of the IGL, identified by their expression of glial fibrillar acidic protein. No MeHg-related effects on Purkinje cells were detected neither at weaning nor at puberty. These findings suggest: (i) a delayed MeHg exposure-related effect on M2- and M3-MRs, (ii) an overt MeHg-related cytotoxic effect on cerebellar oligodendroglia, e.g. reactive gliosis, (iii) a selective vulnerability of granule cells and Purkinje neurons to MeHg, with the latter that remain unharmed.
Roda
Elisa
E
University of Pavia, Department of Internal Medicine and Therapeutics, Toxicology Division, Pavia, Italy. elisa.roda@unipv.it
Coccini
Teresa
T
Acerbi
Davide
D
Castoldi
Anna
A
Bernocchi
Graziella
G
Manzo
Luigi
L
D000818:Animals; D064032:Calbindin 2; D064026:Calbindins; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005260:Female; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006416:Hematoxylin; D007150:Immunohistochemistry; D008297:Male; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism* / Q000473:pathology; D008767:Methylmercury Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064032:Calbindin 2; D064026:Calbindins; D004396:Coloring Agents; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D008767:Methylmercury Compounds; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D064030:S100 Calcium Binding Protein G; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin