Prenatal ethanol exposure reduces spinal cord motoneuron number in the fetal rat but does not affect GDNF target tissue protein.
Fetal rats were exposed throughout gestation to one of three diets: an ethanol-containing liquid diet, a liquid diet with the isocaloric substitution of sucrose for ethanol or a laboratory chow control diet. At postnatal day 1 (P1), the spinal cords were taken for analyses of motoneuron number and size. These analyses revealed a significant loss of motoneurons and a reduction of motoneuron size in the ethanol-exposed animals, compared to both sucrose and chow controls. Spinal cord length and ventral horn volume were not altered as a result of ethanol treatment, so the change in motoneuron number cannot be attributed to volumetric changes. The content of the motoneuron survival factor glial cell-line-derived neurotrophic factor (GDNF) was also assessed in the P1 limb motoneuron target tissue. This analysis was undertaken because GDNF is a potent survival factor for developing motoneurons and has been shown to protect this population from ethanol neurotoxicity. Thus, its depletion could contribute to motoneuron loss. These analyses, using the ELISA assay, did not detect reductions in GDNF in the ethanol-exposed animals. Therefore, alterations in other neurotrophic factors or ethanol neurotoxicity by other means appear to be responsible for the motoneuron loss. These results are consistent with earlier studies in the chick embryo, which also found reduced motoneuron numbers as a function of developmental ethanol exposure, and point again to the general lethality of ethanol to the developing nervous system.
Barrow Heaton
M B
MB
University of Florida Brain Institute, Department of Neuroscience, Center for Alcohol Research, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA. heaton@ufbi.ufl.edu
Kidd
K
K
Bradley
D
D
Paiva
M
M
Mitchell
J
J
Walker
D W
DW
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009046:Motor Neurons / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology
D002492:Central Nervous System Depressants; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000431:Ethanol