Cerebellum cholinergic muscarinic receptor (subtype-2 and -3) and cytoarchitecture after developmental exposure to methylmercury: an immunohistochemical study in rat

J Chem Neuroanat. 2008 May;35(3):285-94. doi: 10.1016/j.jchemneu.2008.01.003. Epub 2008 Feb 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 2
  • Calbindins
  • Cerebellum / metabolism*
  • Cerebellum / pathology
  • Coloring Agents
  • Eosine Yellowish-(YS)
  • Female
  • Fluorescent Dyes
  • Glial Fibrillary Acidic Protein / metabolism
  • Hematoxylin
  • Immunohistochemistry
  • Male
  • Mercury Poisoning, Nervous System / metabolism*
  • Mercury Poisoning, Nervous System / pathology
  • Methylmercury Compounds / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Muscarinic M2 / metabolism*
  • Receptor, Muscarinic M3 / metabolism*
  • S100 Calcium Binding Protein G / metabolism


  • Calbindin 2
  • Calbindins
  • Coloring Agents
  • Fluorescent Dyes
  • Glial Fibrillary Acidic Protein
  • Methylmercury Compounds
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • S100 Calcium Binding Protein G
  • Eosine Yellowish-(YS)
  • Hematoxylin