Cholinergic deafferentation exacerbates seizure-induced loss of somatostatin-immunoreactive neurons in the rat hippocampus.
The loss of somatostatin-immunoreactive neurons and the sprouting of mossy fibers are typical histopathological abnormalities in the hippocampus in experimental and human temporal lobe epilepsy. To investigate whether the development of seizure-induced alterations is regulated by the subcortical afferent pathways to the hippocampus, we lesioned cholinergic, noradrenergic or serotonergic afferent pathways in rats two days after seizures were induced with kainate. Two months later, somatostatin-immunoreactive neurons were counted in the hilus to assess the severity of neuronal damage. Mossy fiber sprouting was analysed from adjacent Timm-stained sections. Kainate-induced seizures caused a loss of hilar somatostatin-immunoreactive neurons in the septal end of the hippocampus, where 63% of the somatostatin-immunoreactive neurons survived. Even more severe damage was found in the temporal end of the hippocampus (only 21% surviving). Cholinergic deafferentation of the hippocampus (using 192-IgG saporin) decreased the overall number of hilar somatostatin-immunoreactive neurons. In control rats that did not receive kainate, 87% (septal end) and 74% (temporal end) of the hilar somatostatin-immunoreactive neurons remained after cholinergic deafferentation. Moreover, seizure-induced damage to hilar somatostatin-immunoreactive neurons was further exacerbated by 192-IgG-saporin, with only 35% of the neurons remaining in the septal end and 14% in the temporal end of the hippocampus. Noradrenergic [using N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] or serotonergic (using 5,7-dihydroxytryptamine) lesions did not affect the number of hilar somatostatin-immunoreactive neurons either in control or in kainate-treated rats. The severity and distribution of seizure-induced mossy fiber sprouting were also not affected by any of the lesions. These data suggest that various subcortical afferent pathways may differentially modulate seizure-induced damage to the hippocampus. Damage to cholinergic neurons results in the loss of hilar somatostatin-immunoreactive neurons and exacerbates the seizure-induced loss of somatostatin-immunoreactive neurons.
Jolkkonen
J
J
A.I. Virtanen Institute, University of Kuopio, Finland.
Kähkönen
K
K
Pitkänen
A
A
D000344:Afferent Pathways / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D000922:Immunotoxins; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009699:N-Glycosyl Hydrolases; D009475:Neurons, Afferent / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D017764:Parasympathectomy; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D018690:Excitatory Amino Acid Agonists; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012701:Serotonin; D013004:Somatostatin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D007608:Kainic Acid; D009638:Norepinephrine