Permanent neuronal deficits in rats exposed to alcohol during the brain growth spurt

Authors

  • Daniel J. Bonthius,

    1. Departments of Pediatrics and Neuroscience, University of Virginia, Charlottesville, Virginia 22908
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  • James R. West Ph.D.

    Corresponding author
    1. Department of Anatomy, University of Iowa, Iowa City, Iowa 52242
    • Alcohol and Brain Research Laboratory, Department of Anatomy, Bowen Science Building, University of Iowa, Iowa City, IA 52242
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Abstract

The purpose of this study was to determine whether developmental alcohol exposure could induce permanent neuronal deficits, whether the peak blood alcohol concentration (BAC) influences the severity of the effects, and whether the effects are gender related. Rat pups were reared artifically over postnatal days (PD) 4 through 11 (a period of rapid brain growth, comparable to part of the human third trimester). Alcohol treatments were administered on PD 4 through 9. Patterns of alcohol exposure that produce different peak BACs have been shown to affect differentially the amount of brain weight deficits and neuron loss shortly after the exposure period, so this study investigated whether the pattern of alcohol exposure was also effective in producing permanent deficits. Two groups received a daily alcohol dose of 4.5 g/kg, condensed into either four or two feedings. A third group received a higher daily alcohol dose of 6.6 g/kg administered in 12 uniformly spaced daily feedings. Pups were fostered back to dams on PD 11 and perfused on PD 90. Brain weights were measured, and Purkinje cells and granule cells were counted in each of the 10 lobules of the cerebellar vermis. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. The groups receiving the lower daily dose (4.5 g/kg) condensed into either four or two feedings were exposed to higher peak BACs and suffered significant permanent brain weight deficits and neuronal losses, relative to controls. The group receiving the higher daily dose (6.6 g/kg) in continuous fractions had no significant brain weight reductions or neuronal loss. Vulnerability to alcohol-induced neuronal loss varied among regions and cell populations and as a function of peak BAC. In the hippocampus, only the CA1 pyramidal cells were significantly reduced in number and only in group receiving the most condensed alcohol treatment. In the cerebellum, the severity of Purkinje cell and granule cell losses varied among lobules, and Purkinje cell vulnerability appeared to depend on the maturational state of the neuron at the time of the alcohol exposure, with the more mature Purkinje cells being the more vulnerable.

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