Methylmercuric chloride induces activation of neuronal stress circuitry and alters exploratory behavior in the mouse.
Methylmercury (MeHg) is a well-known neurotoxicant, responsible for neurological and cognitive alterations. However, there is very little information available on the effects of MeHg administration on activation of murine neuronal pathways involved in the stress response, and whether this is altered as a function of repeated exposure to MeHg. Moreover, interactions between MeHg and other psychogenic and inflammatory stressors have yet to be fully determined. Acute i.p. exposure of male C57BL/6J mice to MeHg (2-8 mg/kg) dose-dependently attenuated exploratory behavior in the open field in the presence and absence of a novel object. In addition, increased numbers of c-Fos immunoreactive cells appeared in response to acute i.p. and i.c.v. MeHg within thalamic (anterior paraventricular nucleus of the thalamus (PVA)/posterior paraventricular nucleus of the thalamus (PV)), hypothalamic (paraventricular nucleus of the hypothalamus (PVN)), central amygdaloid nucleus (CeC), septal and hippocampal (dentate gyrus) nuclei, medial bed nucleus (BSTm) and the locus coeruleus (Lc). The increase in c-Fos positive cells in response to acute i.p. and i.c.v. MeHg did not appear to be influenced further by open field exposure. Repeated administration of MeHg led to an attenuation of most parameters of open field behavior altered by acute MeHg. However, increased c-Fos was significant in the CeC, Dg, supracapsular bed nucleus (BSTs), and Lc. Moreover, open field exposure after repeated treatments resulted in significant c-Fos responses in similar areas. Interestingly, 3 days after the final repeated MeHg dose (2 or 4 mg/kg) c-Fos increases to an immunogenic stressor (LPS) were not affected by MeHg pretreatment. These results demonstrate that systemic exposure to acute and repeated MeHg serves to activate the brain's stress circuitry, and furthermore appears to engage normal neuronal habituation processes.
Cooper
J F
JF
Joint Graduate Program in Toxicology-Rutgers University/University of Medicine and Dentistry of New Jersey, USA.
Kusnecov
A W
AW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*
D008767:Methylmercury Compounds; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; C004925:methylmercuric chloride