Effects of neonatal alcohol exposure during different periods of brain development on cerebellar cell loss and eyeblink classical conditioning in adult Long -Evans rats

Timothy B Johnson, Purdue University

Abstract

Experimental studies in a neonatal rat model of binge-like alcohol exposure during the “third-trimester equivalent” tested the hypothesis that the timing of an alcohol insult during early brain development would be a crucial mediator of the type and severity of ensuing neuropathology. Two groups of neonatal rats were given binge-like alcohol exposure (5.25 g/kg/day, peak BACs ∼420 mg/dl) via intragastric intubation, during either postnatal days (PD) 4-6 or PD 7-9. Littermates given sham intubations served as intubated controls, and a separate group of untreated controls was derived from contemporaneous litters. Eyeblink classical conditioning was initiated around PD 90, and rats were randomly assigned to one of three training conditions: (1) twelve days of trace conditioning; (2) twelve days of long-delay eyeblink classical conditioning; (3) six days of short-delay eyeblink conditioning followed by six days of long-delay conditioning (ISI-Shift). Following eyeblink training, brains were extracted from ISI-Shift males and stereological counts of cerebellar Purkinje cells and neurons of the interpositus nucleus were obtained. PD 4-6 exposure caused significant associative learning deficits, but only during the short-delay phase of training, and unexpectedly, only in females. There were no CR timing deficits in the PD 4-6 alcohol exposure group when the ISI was shifted from 280 to 880-ms, nor were trace (or long-delay) conditioning deficits evident in the PD 7-9 alcohol exposure group. Cell count data confirmed enhanced vulnerability of cerebellar Purkinje cells to alcohol insult during PD 4-6, and additionally revealed differential regional Purkinje cell vulnerability. The PD 4-6 exposure group had significantly fewer Purkinje cells than either control group in the anterior lobes and lobule simplex, and had significantly fewer Purkinje cells than the PD 7-9 group in the anterior lobes. The PD 7-9 group had significantly lower mean Purkinje cell counts than unintubated controls in both regions, but did not differ significantly from sham-intubated controls in either case. Significant loss of neurons in the interpositus nucleus was only seen following PD 4-6 exposure. These results provided support for the hypothesis that the timing of alcohol insult during early brain development is a determinant of the type and severity of resulting brain damage.

Degree

Ph.D.

Advisors

Goodlett, Purdue University.

Subject Area

Neurosciences|Behavioral psychology|Developmental psychology

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