The concept of astrocyte-kinetic drug in the treatment of neurodegenerative diseases: evidence for L-deprenyl-induced activation of reactive astrocytes.
Basic fibroblast growth factor (bFGF) increases neuronal survival and growth in cell cultures and stimulates functional recovery from brain lesion. In addition, bFGF is able to induce glial cell proliferation and differentiation. Recently, L-deprenyl has been shown to potentiate astrocyte reaction to a mechanical lesion and to possess a trophic-like activity in several experimental models. In the present paper, we have therefore investigated if the enhancing effect of L-deprenyl on astrocyte reactivity is accompanied by increased levels of bFGF. The effect of L-deprenyl (0.25 mg/kg/day) on bFGF immunoreactivity (IR) after the insertion of an injection cannula in rat neostriatum have been investigated. It has been found that subchronic L-deprenyl treatment potentiates both the lesion-induced increase of glial fibrillary acidic protein (GFAP) and bFGF IRs (P < 0.01). These data suggest that a possible mechanism for L-deprenyl-induced neuroprotection may be the activation of astrocytes associated with increased secretion of trophic factors that promote neuronal survival and growth. This "astrocyte-kinetic" action of L-deprenyl could represent a new therapeutical approach to increase trophic support of lesioned neurons.
Institute of Human Physiology, University of Modena, Italy.
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Biagini
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Frasoldati
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Fuxe
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Agnati
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003720:Densitometry; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000033:anatomy & histology / Q000502:physiology; D009410:Nerve Degeneration / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*
D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D012642:Selegiline