Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum.
Ethanol causes loss of Purkinje cells in the cerebellum during the early stages of differentiation and maturation by a presently unknown mechanism. Neuronal vulnerability in the cerebellum parallels the prominent temporal and anatomical gradients of development (i.e. early to late interlobular and posterior to anterior, respectively). Development of Purkinje cells is known to require binding of the neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3), to the tyrosine-kinase (Trk) receptors TrkB and TrkC, respectively. In addition, Purkinje cells are reported to experience a critical switch between BDNF dependence and NT3 dependence during the period of highest ethanol sensitivity between postnatal days (PN) 4-6. To test the hypothesis that ethanol alters neurotrophin signaling leading to Purkinje neuronal death, the immunohistochemical expression of TrkB and TrkC receptors on Purkinje cells of rat pups following a moderate dose of ethanol was determined at various times surrounding the period of postnatal ethanol vulnerability. Ethanol selectively decreased Purkinje cell expression of TrkB and TrkC receptors following exposures within the vulnerable period (PN4-6). These results suggest that ethanol may induce loss of Purkinje cells by alteration of neurotrophic regulation at this critical stage.
Light
Kim E
KE
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205, USA. lightkime@uams.edu
Brown
Donna P
DP
Newton
Bruce W
BW
Belcher
Scott M
SM
Kane
Cynthia J M
CJ
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002525:Cerebellar Cortex / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D011247:Pregnancy; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D000431:Ethanol; D020813:Receptor, trkB; D020812:Receptor, trkC