Gustus Kymberly, Li Lu, Newville Jessie, Cunningham Lee Anna
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Brain Plast. 2020 Dec 29;6(1):67-82. doi: 10.3233/BPL-200112.
Fetal alcohol spectrum disorders (FASDs) are associated with a wide range of cognitive deficiencies.
We previously found that gestational exposure to moderate levels of alcohol in mice throughout the 1st-2nd human trimester-equivalents for brain development results in profound impairment of the hippocampal neurogenic response to enriched environment (EE) in adulthood, without altering baseline neurogenesis rate under standard housing (SH). However, the functional and structural consequences of impaired EE-mediated neurogenesis in the context of prenatal alcohol exposure (PAE) have not been determined.
Here, we demonstrate that PAE-EE mice display impaired performance on a neurogenesis-dependent pattern discrimination task, broadened behavioral activation of the dentate gyrus, as assessed by expression of the immediate early gene, c-Fos, and impaired dendritic branching of adult-generated dentate granule cells (aDGCs).
These studies further underscore the impact of moderate gestational alcohol exposure on adult hippocampal plasticity and support adult hippocampal neurogenesis as a potential therapeutic target to remediate certain neurological outcomes in FASD.
胎儿酒精谱系障碍(FASDs)与多种认知缺陷相关。
我们之前发现,在小鼠大脑发育的相当于人类孕早期第1至2个阶段期间,孕期暴露于中等水平的酒精会导致成年后海马体对丰富环境(EE)的神经发生反应严重受损,而在标准饲养(SH)条件下不会改变基线神经发生率。然而,在产前酒精暴露(PAE)背景下,EE介导的神经发生受损的功能和结构后果尚未确定。
在此,我们证明PAE-EE小鼠在依赖神经发生的模式辨别任务中表现受损,齿状回的行为激活范围扩大,这通过即刻早期基因c-Fos的表达来评估,并且成年生成的齿状颗粒细胞(aDGCs)的树突分支受损。
这些研究进一步强调了孕期中等程度酒精暴露对成年海马可塑性的影响,并支持成年海马神经发生作为改善FASD某些神经学结果的潜在治疗靶点。