Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.
The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular / Q000379:methods; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D010320:Parvalbumins; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013194:Staining and Labeling
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D007608:Kainic Acid