ObjectivePrenatal alcohol exposure can result in neurological changes in affected individuals and may result in the emergence of a broad spectrum of neurobehavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The effects of ethanol exposure during development are both time and dose dependent. Although many animal models of FASD use more chronic ethanol exposure, acute developmental alcohol exposure may also cause long‐lasting neuronal changes. Our research employed behavioral measures to assess the effects of a single early postnatal ethanol intoxication event in mice.Materials and MethodsMice were dosed at postnatal day 6 (a 2.5 g/kg dose of ethanol or a saline control administered twice, 2 hr apart) as a model of third trimester binge drinking in humans. This exposure was followed by behavioral assessment in male mice at 1 month (1M) and at 4 months of age (4M), using the Barnes maze (for learning/memory retrieval), exploratory behavior, and a social responsiveness task.ResultsEthanol‐exposed mice appeared to be less motivated to complete the Barnes maze at 1M, but were able to successfully learn the maze. However, deficits in long‐term spatial memory retrieval were observed in ethanol‐exposed mice when the Barnes maze recall was measured at 4M. No significant differences were found in open field behavior or social responsiveness at 1M or 4M of age.ConclusionsAcute ethanol exposure at P6 in mice leads to mild but long‐lasting deficits in long‐term spatial memory. Results suggest that even brief acute exposure to high ethanol levels during the third trimester equivalent of human pregnancy may have a permanent negative impact on the neurological functioning of the offspring.
Huntington disease (HD) is a neurodegenerative disorder that is caused by an elongation of a normally occurring polyglutamine stretch within the huntingtin (HTT) protein. Since the mutation was first identified, multiple HD‐disease‐modifying gene candidates that can hasten or delay age of onset (AO) have been discovered. For the past several decades, candidate disease‐modifying genes have been chosen for investigation based on functionality or prior implication in the disease process. More recent approaches take advantage of newly available genomic‐wide assays to identify changes as small as single‐nucleotide polymorphisms (SNPs) in other parts of the genome. New information regarding disease‐modifying genes will continue to elucidate potential HD therapeutic candidates. Key Concepts Huntington disease is a neurodegenerative disease that results from excess CAG trinucleotide repeats in exon 1 of the HD gene, which is located in chromosome 4p16.3 and encodes the HTT protein. The number of CAG repeats in the HD gene inversely affects the age of onset (AO) in HD patients. Genetic modifiers are identified genes that have the ability to either hasten or delay AO of HD; however, the exact mechanism of many of these genes in association with the disease is unknown. HD genetic modifiers can significantly delay specific physiological HD symptoms, such as chorea. Some HD genetic modifiers can alter HD AO by up to 8 years. Genetic modifiers have been discovered by either the candidate approach, which involves exploring genes known to be associated with the HTT protein and genotyping any variants, or via a more unbiased genomic approach, which involves a broad search for genes that are not known to be associated with the HTT protein. Modifiers that affect HD do not necessarily need to be within close vicinity of the actual gene, but can be distributed elsewhere in the genome, even in noncoding regions.
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