Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat.
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.
Pierce
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Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W Markham Street, #522-3 Little Rock, AR 72205-7199, USA. piercedwight@uams.edu
Hayar
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Williams
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Light
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D000818:Animals; D000831:Animals, Newborn; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count; D002470:Cell Survival; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D009847:Olivary Nucleus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D000431:Ethanol