Entorhinal cortex lesion induces differential responses in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in the rat hippocampal formation.
The hippocampus can be induced by deafferentation to selectively reorganize its neuronal input. Entorhinal cortex lesion, which causes degeneration of the perforant pathway, evokes sprouting of septal afferents as well as glutamatergic commissural/associational fibers in the deafferentated zone of the molecular layer of the dentate gyrus. Although the process of reactive synaptogenesis that follows deafferentation has been extensively studied, at present little is known about its molecular basis and the mechanism of initiation. In this study, following unilateral lesion of the entorhinal cortex, the time-course of possible alterations of insulin-like growth factors I and II, and insulin binding sites were evaluated by in vitro quantitative receptor autoradiography. [125I]Insulin-like growth factor I receptor binding sites did not exhibit any significant variation between the contralateral and ipsilateral hippocampal formation at any time periods following lesion except in the molecular layer of the dentate gyrus (P < 0.05) at day 8. However, when compared with the unlesioned animals, a differential time-dependent response of [125I]insulin-like growth factor I binding sites was noted in selective layers of the hippocampus. [125I]Insulin-like growth factor II receptor binding sites showed a significant decrease (P < 0.05) in the ipsilateral granular cell layer of the dentate gyrus only at day 14 post lesion. Interestingly, compared to controls, a dramatic bilateral increase (P < 0.05) in [125I]insulin-like growth factor II binding was evident between days 1 and 8 in most layers of the hippocampal formation. A lesion-induced bilateral increase (P < 0.05) in [125I]insulin binding sites was evident in all layers of the hippocampus between two to eight days and at 30 days post lesion. In selective layers, however, a significant increase (P < 0.05) in [125I]insulin binding sites was also observed at days 1 and 14 after lesion. These results, which are compatible with the process of degeneration and/or sprouting of the terminal fibers, suggest possible involvement of insulin-like growth factors and insulin in the sequence of molecular events that occur to facilitate neuronal repair and to promote neuronal survival following entorhinal cortex lesion.
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Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Canada.
Baccichet
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Quirion
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Poirier
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D000344:Afferent Pathways / Q000293:injuries / Q000503:physiopathology; D000818:Animals; D003720:Densitometry; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000293:injuries* / Q000503:physiopathology; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis* / Q000235:genetics; D011972:Receptor, Insulin / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D017527:Receptor, IGF Type 2; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin