Methanol-induced neurotoxicity in pups exposed during lactation through mother: role of folic acid.
Role of folic acid on methanol-induced neurotoxicity was studied in pups at Postnatal Day (PND) 45 exposed to methanol (1%, 2% and 4%, v/v) during lactation through mothers maintained on folic acid-deficient (FD) and folic acid-sufficient (FS) diet. A gradual loss in the body weight gain was observed in the pups exposed to 2% and 4% methanol in the FD group, while FS group exhibited this alteration only at 4% exposure. The assessment of spontaneous locomotor activity (SLA) showing a significant increase in the distance travelled was observed in the 2% and 4% methanol-exposed groups in both the FS and FD animals when compared with their respective controls, but the effect was more marked in the FD group. A significant decrease in the conditioned avoidance response (CAR) was observed in pups exposed to 2% and 4% methanol in the FD group at PND 45. The results also suggest that disturbances in dopaminergic and cholinergic receptors were more pronounced in the FD group as compared to the FS group. A significant decrease in striatal dopamine levels was also observed in the FD group at 2% and 4% methanol exposure, while in the FS group, a significant decrease was exhibited only at 4% methanol exposure. An aberrant increase in the expression of Growth-Associated Protein (GAP-43), a neuron-specific growth-associated protein was observed in pups in the FD group exposed to 2% and 4% methanol, while an increase in the expression of GAP-43 in the FS group was found only at 4% methanol exposure in the hippocampal region as compared to their respective controls. Results suggests that methanol exposure during growth spurt period adversely affects the developing brain, the effect being more pronounced in FD rats as compared to FS rats, suggesting a possible role of folic acid in methanol-induced neurotoxicity.
Predictive Toxicology Group, Developmental Toxicology Division, Industrial Toxicology Research Centre, Post Box No. 80, M.G. Marg, Lucknow, India.
Moammir Hasan
MH
Aziz
Ashok Kumar
AK
Agrawal
Vaqar Mustafa
VM
Adhami
Mohammad M
MM
Ali
Masroor A
MA
Baig
Prahlad Kishore
PK
Seth
D000818:Animals; D000833:Animals, Suckling; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology*; D019922:GAP-43 Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007774:Lactation; D000432:Methanol / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*
D065127:Dopamine D2 Receptor Antagonists; D019922:GAP-43 Protein; D011976:Receptors, Muscarinic; D012997:Solvents; D005492:Folic Acid; D004298:Dopamine; D000432:Methanol