Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats.
Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.
Departmento de Fisiologia da EPM-UNIFESP, São Paulo-SP, Brazil.
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C
Hamani
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Tenório
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Mendez-Otero
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Mello
D000818:Animals; D015415:Biomarkers; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000187:drug effects; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis*; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000032:analysis*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D010862:Pilocarpine; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase