Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat

• Published in: Neuroscience 2010-09, Vol.169 (3), p.1438-1448
• Main Authors: Pierce, D.R, Hayar, A, Williams, D.K, Light, K.E
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Antibodies; Biological and medical sciences; Calbindin 1; Calbindins; Cell Count; Cell Survival; Cerebellar Cortex - cytology; Cerebellar Cortex - drug effects; Cerebellar Cortex - growth & development; confocal; development; Ethanol - blood; Ethanol - pharmacology; Fundamental and applied biological sciences. Psychology; Imaris; Neurology; Olivary Nucleus - drug effects; Olivary Nucleus - growth & development; Olivary Nucleus - physiology; Purkinje cell; Purkinje Cells - cytology; Purkinje Cells - drug effects; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G - metabolism; Synapses - drug effects; Synapses - ultrastructure; Time Factors; Vertebrates: nervous system and sense organs; Vesicular Glutamate Transport Protein 2 - metabolism; VGluT2
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.06.008

Abstract Ethanol exposure during postnatal days (PN) 4–6 in rats alters cerebellar development resulting in significant loss of Purkinje cells. There is little knowledge, however, on what happens to the neurons that survive. In this study, rat pups were treated with a daily dose of ethanol (either 3.6 or 4.5 g/kg body weight) delivered by intragastric intubation on PN4, PN4–6, or PN7–9. Then the interactions between climbing fibers and Purkinje cells were examined on PN14 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced in the PN4 and PN4–6 ethanol groups for the 4.5 g/kg dose level, compared to controls, indicating that the cerebellar circuitry was significantly altered following developmental ethanol exposure. Not only were there fewer Purkinje cells following ethanol exposure, but the surviving neurons had significantly fewer VGluT2-labeled synapses. These alterations in the synaptic integrity were both dose dependent and temporally dependent.