Neonatal ethanol causes profound reduction of cholinergic cell number in the basal forebrain of adult animals
| Autor: | Cynthia Bleiwas, Cátia M. Teixeira, Robert M. Sears, Stefanie Canals-Baker, John F. Smiley, Mariko Saito, Donald A. Wilson, Sharifa Z. Williams |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Health (social science) Basal Forebrain Cholinergic Agents Cell Count Striatum Biology Toxicology Nucleus basalis Biochemistry Article Choline O-Acetyltransferase Mice Behavioral Neuroscience Pregnancy Dopamine Internal medicine medicine Animals Basal forebrain Ethanol Substantia innominata General Medicine Mice Inbred C57BL Ventral tegmental area Endocrinology medicine.anatomical_structure nervous system Neurology Forebrain Cholinergic Female medicine.drug |
| Zdroj: | Alcohol |
| ISSN: | 0741-8329 |
| Popis: | In animal models that mimic human third-trimester fetal development, ethanol causes substantial cellular apoptosis in the brain, but for most brain structures, the extent of permanent neuron loss that persists into adulthood is unknown. We injected ethanol into C57BL/6J mouse pups at postnatal day 7 (P7) to model human late-gestation ethanol toxicity, and then used stereological methods to investigate adult cell numbers in several subcortical neurotransmitter systems that project extensively in the forebrain to regulate arousal states. Ethanol treatment caused especially large reductions (34–42%) in the cholinergic cells of the basal forebrain, including cholinergic cells in the medial septal/vertical diagonal band nuclei (Ch1/Ch2) and in the horizontal diagonal band/substantia innominata/nucleus basalis nuclei (Ch3/Ch4). Cell loss was also present in non-cholinergic basal forebrain cells, as demonstrated by 34% reduction of parvalbumin-immunolabeled GABA cells and 25% reduction of total Nissl-stained neurons in the Ch1/Ch2 region. In contrast, cholinergic cells in the striatum were reduced only 12% by ethanol, and those of the brainstem pedunculopontine/lateral dorsal tegmental nuclei (Ch5/Ch6) were not significantly reduced. Similarly, ethanol did not significantly reduce dopamine cells of the ventral tegmental area/substantia nigra or serotonin cells in the dorsal raphe nucleus. Orexin (hypocretin) cells in the hypothalamus showed a modest reduction (14%). Our findings indicate that the basal forebrain is especially vulnerable to alcohol exposure in the late gestational period. Reduction of cholinergic and GABAergic projection neurons from the basal forebrain that regulate forebrain arousal may contribute to the behavioral and cognitive deficits associated with neonatal ethanol exposure. |
| Databáze: | OpenAIRE |
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