Smith Grace C, Griffith Keith R, Sicher Avery R, Brockway Dakota F, Proctor Elizabeth A, Crowley Nicole A
Department of Biology, The Pennsylvania State University, University Park, PA, USA 16802.
Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA 16802.
bioRxiv. 2024 Apr 5:2024.04.03.587955. doi: 10.1101/2024.04.03.587955.
Both alcohol use disorder (AUD) and Alzheimer's Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on Alzheimer's Disease progression in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor.
酒精使用障碍(AUD)和阿尔茨海默病及相关痴呆症(ADRD)似乎都包括皮质兴奋与抑制平衡的破坏,但其潜在相互作用尚不清楚。我们通过测量小鼠长时间戒酒前额叶皮质锥体(兴奋性、谷氨酸能)和非锥体(抑制性、γ-氨基丁酸能)神经元的内在兴奋性和自发神经传递,研究了适度自愿暴饮酒精对衰老的疾病前神经元环境的影响。结果表明,暴饮酒精对前额叶皮质神经元的电生理特性有持久影响。饮酒后,观察到对第2/3层非锥体神经元的兴奋性事件显著增加,同时锥体神经元的内在兴奋性也发生改变,这可能对人类阿尔茨海默病的进展产生一系列影响。这些结果表明,适度自愿饮酒会影响衰老过程中的疾病前环境,并强调需要对这一风险因素进行进一步的机制研究。