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Acute and Long-Term Purkinje Cell Loss Following a Single Ethanol Binge During the Early Third Trimester Equivalent in the Rat

Authors


Reprint requests: Ruth Napper, Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand; Tel.: +64 3 479 7367; Fax: +64 3 479 7254; E-mail: ruth.napper@anatomy.otago.ac.nz

Abstract

Background

In the rat, binge-like ethanol (EtOH) exposure during the early neonatal period (a developmental period equivalent to the human third trimester) can result in a permanent deficit of cerebellar Purkinje cells (Pcells). However, the consequences of a moderate binge alcohol exposure on a single day during this postnatal period have not been established. This is an issue of importance as many pregnant women binge drink periodically at social drinking levels. This study aimed to identify both the acute and long-term effects of exposure to a single alcohol binge that achieved a mean peak blood EtOH concentration of approximately 250 mg/dl during early postnatal life using a rat model of fetal alcohol spectrum disorders.

Methods

Acute apoptotic Pcell death 10 hours after a moderate dose binge EtOH exposure from postnatal days (PDs) 0 to 10 was assessed using active caspase-3 immunolabeling. Acute Pcell apoptosis was quantified in cerebellar vermal lobules I–X using the physical disector method. Long-term effects were assessed at PD 60 using stereological methods to determine total Pcell numbers in the vermis, lobule III, and lobule IX, following a moderate dose binge EtOH exposure at PDs 0, 2, or 4.

Results

Acute apoptosis was induced by EtOH on PDs 1 to 8 in a time and lobular-dependent manner. For EtOH exposure on PD 2, significant long-term Pcell loss occurred in lobule III. EtOH exposure on PD 4 resulted in significant long-term Pcell loss throughout the entire vermis.

Conclusions

These results indicate that a single, early EtOH episode of moderate dose can create significant and permanent Pcell loss in the developing cerebellum.

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