Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat
| Autor: | Dwight R. Pierce, Kim E. Light, Scott M. Belcher |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Calbindins Programmed cell death Cerebellum Time Factors Purkinje cell Apoptosis Cytochrome c Group Drug Administration Schedule Rats Sprague-Dawley Cerebellar Cortex Purkinje Cells Immunolabeling S100 Calcium Binding Protein G Alcohol-Induced Disorders Nervous System Pregnancy In Situ Nick-End Labeling medicine Animals Ethanol biology Caspase 3 General Neuroscience Cytochrome c Immunohistochemistry Mitochondria Rats Cell biology medicine.anatomical_structure Animals Newborn Biochemistry Calbindin 1 Fetal Alcohol Spectrum Disorders Caspases Prenatal Exposure Delayed Effects Cerebellar cortex Nerve Degeneration biology.protein Female Neurotrophin |
| Zdroj: | Neuroscience. 114:327-337 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/s0306-4522(02)00344-5 |
| Popis: | The present study was designed to evaluate the time course and manner of Purkinje cell death following a single ethanol dose delivered intragastrically on postnatal day (PN) 4 to rat pups. Analysis included immunolabeling of Purkinje cells with antibody specific for calbindin D28k and counting of Purkinje cells in each lobule of a mid-vermal slice. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis and immunodetection for cleaved (activated) caspase-3 enzyme was used to identify apoptosis, with calbindin D28k co-immunolabeling to identify apoptotic Purkinje cells. Finally, immunodetection for cytochrome c, again with co-labeling using calbindin D28k antibody, identified intracellular release of cytochrome c from the mitochondria into the cytoplasm of Purkinje cells. The data demonstrate that a single dose of ethanol results in a significant and extensive, lobular dependent loss of Purkinje cells within 24 h after administration. Extensive loss in the early developing lobules (I-III, VIII-X) and less to no loss in the later developing lobules (IV-VII) is consistent with prior literature reports on the ethanol-induced effects on Purkinje cells at this age. Clear and consistent evidence of apoptotic Purkinje cells was identified and the pattern was transient in nature. Finally, cytochrome c is released from the mitochondria of Purkinje cells in a time course consistent with the activation of the mitochondrial pathway of apoptosis. These data support the hypothesis that ethanol-induced loss of Purkinje cells involves apoptotic mechanisms. Furthermore, the initiation of apoptosis by ethanol is consistent with ethanol-induced interruptions of Purkinje cell neurotrophic support leading to activation of the mitochondrial pathway of apoptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect