Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low blood alcohol levels during the brain growth spurt: A stereological investigation
Article first published online: 10 OCT 2004
Copyright © 1995 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 362, Issue 2, pages 283–292, 13 November 1995
How to Cite
Napper, R. M. A. and West, J. R. (1995), Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low blood alcohol levels during the brain growth spurt: A stereological investigation. J. Comp. Neurol., 362: 283–292. doi: 10.1002/cne.903620210
- Issue published online: 10 OCT 2004
- Article first published online: 10 OCT 2004
- Manuscript Accepted: 24 MAR 1995
- fetal alcohol syndrome;
- purkinje cell;
- granule cell;
- stereological methods
This study demonstrates that exposure to an alcohol regimen that resulted in low, uniform blood alcohol concentrations during a period of rapid brain growth can lead to a permanent deficit in the number of Purkinje cells and granule cells in the floccular-parafloccular region of the cerebellum. Sprague-Dawley rat pups were artificially reared and were administered alcohol over postnatal days 4 through 9, a period of brain development similar to that of the human third trimester. Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 10.2% solution in two of the 12 daily feedings (10.2% group) or as a 5.1% solution in four of the 12 feedings (5.1% group). A third group received a daily dose of 6.6 g/kg administered as a 2.5% solution in every feeding (2.5% group). The condensed patterns of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance while the higher daily dose (6.6 g/kg), administered continuously, resulted in low but continuous blood alcohol concentrations. Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of Purkinje cells and granule cells in the floccular-parafioccular region of the cerebellum was estimated using unbiased stereological methods. Exposure to alcohol resulted in significant deficits in the number of both Purkinje cells and granule cells at 115 days of age in all three treatment groups. Most importantly a significant deficit of Purkinje cells and granule cells was found following continuous exposure to low blood alcohol concentrations, i.e., in the 2.5% group. The total number of Purkinje cells in the 2.5% group was 2.33 ± 0.31 x 104 compared with 3.18 ± 0.30 x 104 in the artificially reared controls. The total number of granule cells in the 2.5% group and the controls was 1.24 ± 0.10 x 107 and 1.64 ± 0.19 x 107 respectively.
These results support the hypothesis that exposure to a continuous, low blood alcohol concentration can result in the death of developing neurons and lead to permanent neuronal deficits. The degree of neuronal loss does not correlate with the magnitude of the peaks of blood alcohol concentration © Wiley-Liss, Inc.