Glial-derived neurotrophic factor rescues calbindin-D28k-immunoreactive neurons in alcohol-treated cerebellar explant cultures.
Ethanol exposure during development leads to alterations in neuronal differentiation and profound neuronal loss in multiple regions of the developing brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms that ameliorate ethanol-induced Purkinje cell loss have not been well defined. Previous research indicates that glial-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family, promotes the survival of several neuronal populations, including cerebellar Purkinje cells. Therefore, we examined whether GDNF could attenuate ethanol-induced Purkinje cell loss in an in vitro model system using calbindin-D28k immunoreactivity as a specific marker for Purkinje cells. We found that ethanol led to a significant dose-related decline in calbindin-D28k-immunoreactive cells in explant cultures of the developing cerebellum. However, concurrent administration of GDNF led to a significant rescue of calbindin-D28k-immunoreactive cells. Therefore, our results suggest that GDNF prevents ethanol-associated Purkinje cell loss.
McAlhany
R E
RE
Department of Human Anatomy and Medical Neurobiology, Texas A&M University Health Science Center, College Station 77843-1114, USA.
West
J R
JR
Miranda
R C
RC
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D063647:Fetal Alcohol Spectrum Disorders; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*
C576498:CALB1 protein, human; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D002492:Central Nervous System Depressants; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D018125:Receptors, Transforming Growth Factor beta; D064030:S100 Calcium Binding Protein G; D000431:Ethanol