Participation of NMDA-glutamatergic receptors in hippocampal neuronal damage caused by adult-onset hypothyroidism.
We analyzed the participation of N-methyl-d-aspartate (NMDA) receptors in the neuronal damage caused by adult-onset hypothyroidism. Wistar rats were randomly assigned into four groups. The euthyroid group received tap water. The hypothyroid group received methimazole (60 mg/kg) in their drinking water to induce hypothyroidism. Two more groups of rats received the antithyroid treatment and were injected daily with the NMDA antagonist ketamine (15 mg/kg, sc) or MK-801 (0.5mg/kg, ip). Treatments were administered during 4 weeks. At the end of the respective treatments rats were deeply anaesthetized and perfused intracardially with 0.9% NaCl followed by 4% paraformaldehyde. The brains were removed from the skull, and coronal brain sections (7microm thick) were obtained. Neurons were counted in the CA1, CA2, CA3, and CA4 hippocampal regions differentiating between normal and atrophic cells by an experimenter blind to the treatment. The percentage of neuronal damage found in the MMI group was significantly greater in the hippocampal regions compared to the euthyroid group. In contrast, both NMDA antagonists were able to prevent the neuronal damage secondary to hypothyroidism in all hippocampal regions. Our results suggest that the neuronal damage caused in the hippocampus of adult-onset hypothyroid rats requires activation of NMDA channels.
Departamento de Fisiología Mauricio Russek, Escuela Nacional de Ciencias Biológicas-IPN, México D.F., Mexico.
Claudia
C
Alva-Sánchez
Adriana
A
Becerril
Brenda
B
Anguiano
Carmen
C
Aceves
Jorge
J
Pacheco-Rosado
D000818:Animals; D013956:Antithyroid Agents; D002452:Cell Count; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008713:Methimazole; D009474:Neurons / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D013956:Antithyroid Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008713:Methimazole; D007649:Ketamine; D016291:Dizocilpine Maleate