Effects of Early Postnatal Exposure to Ethanol on Retinal Ganglion Cell Morphology and Numbers of Neurons in the Dorsolateral Geniculate in Mice
Article first published online: 8 JUN 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 11, pages 2063–2074, November 2011
How to Cite
Dursun, I., Jakubowska-Doğru, E., van der List, D., Liets, L. C., Coombs, J. L. and Berman, R. F. (2011), Effects of Early Postnatal Exposure to Ethanol on Retinal Ganglion Cell Morphology and Numbers of Neurons in the Dorsolateral Geniculate in Mice. Alcoholism: Clinical and Experimental Research, 35: 2063–2074. doi: 10.1111/j.1530-0277.2011.01557.x
- Issue published online: 1 NOV 2011
- Article first published online: 8 JUN 2011
- Received for publication December 8, 2010; accepted March 19, 2011.
- Postnatal Ethanol;
- Yellow Fluorescent Protein Mice;
- Retinal Ganglion Cell Morphology;
- Stereological Cell Counts
Background: The adverse effects of fetal and early postnatal ethanol intoxication on peripheral organs and the central nervous system are well documented. Ocular defects have also been reported in about 90% of children with fetal alcohol syndrome, including microphthalmia, loss of neurons in the retinal ganglion cell (RGC) layer, optic nerve hypoplasia, and dysmyelination. However, little is known about perinatal ethanol effects on retinal cell morphology. Examination of the potential toxic effects of alcohol on the neuron architecture is important because the changes in dendritic geometry and synapse distribution directly affect the organization and functions of neural circuits. Thus, in the present study, estimations of the numbers of neurons in the ganglion cell layer and dorsolateral geniculate nucleus (dLGN), and a detailed analysis of RGC morphology were carried out in transgenic mice exposed to ethanol during the early postnatal period.
Methods: The study was carried out in male and female transgenic mice expressing yellow fluorescent protein (YFP) controlled by a Thy-1 (thymus cell antigen 1) regulator on a C57 background. Ethanol (3 g/kg/d) was administered to mouse pups by intragastric intubation throughout postnatal days (PDs) 3 to 20. Intubation control (IC) and untreated control (C) groups were included. Blood alcohol concentration was measured in separate groups of pups on PDs 3, 10, and 20 at 4 different time points, 1, 1.5, 2, and 3 hours after the second intubation. Numbers of neurons in the ganglion cell layer and in the dLGN were quantified on PD20 using unbiased stereological procedures. RGC morphology was imaged by confocal microscopy and analyzed using Neurolucida software.
Results: Binge-like ethanol exposure in mice during the early postnatal period from PDs 3 to 20 altered RGC morphology and resulted in a significant decrease in the numbers of neurons in the ganglion cell layer and in the dLGN. In the alcohol exposure group, out of 13 morphological parameters examined in RGCs, soma area was significantly reduced and dendritic tortuosity significantly increased. After neonatal exposure to ethanol, a decrease in total dendritic field area and an increase in the mean branch angle were also observed. Interestingly, RGC dendrite elongation and a decrease in the spine density were observed in the IC group, as compared to both ethanol-exposed and pure control subjects. There were no significant effects of alcohol exposure on total retinal area.
Conclusions: Early postnatal ethanol exposure affects development of the visual system, reducing the numbers of neurons in the ganglion cell layer and in the dLGN, and altering RGCs’ morphology.