Sex-specific signatures on macroscopic structural brain connectome following chronic alcohol exposure in mice using high resolution diffusion MR
Project Team
Tanzil Arefin, Assistant Research Professor, Biomedical Engineering
Project Description
Alcohol use disorder (AUD) is a chronic relapsing disorder, characterized by excessive alcohol drinking and loss of control over consumption, and has dramatic consequences for individuals’ health and productivity, their families, and society. Emerging studies suggest that at the neurobiological level, alcohol acts as a complex drug that modifies the activity of multiple molecular targets and triggers broad alterations of gene expression and synaptic plasticity. Excessive alcohol consumption is therefore associated with significant changes in brain morphology including degradation in white matter (WM) integrity that carries information between gray matter (GM) regions and modifying the neural networks responsible for reward, mood, and decision making. There is some evidence that women are more susceptible to alcohol induced brain changes, however the data remains inconclusive. By using an animal model, we can systematically examine the consequences of chronic alcohol exposure in male and female rodents. Specifically, we can evaluate structural, and neuro-architecture changed by chronic alcohol exposure. Over the past decades, tremendous efforts have been made in mapping neural architecture at various scales, such as delineating white matter tracts by mesoscopic tracing of axonal projections, to the identification of cellular-level connections and the synaptic molecular properties. However, this technique relies on the assessment of a single brain, and thus quantitative assessment of neuronal reorganization in multiple sexes or between drug treatments remains a challenge. Hence, the broad goal of this study is to establish a framework to understand the causative link between chronic alcohol exposure and resulting brain structural connectome specific to sex by cross-examination of male and female C57BL/6J mice using high-resolution diffusion MRI (dMRI). The outcome of our proposed study will therefore stand out as a prevailing workbench for neuroscientists to study sex differences in the development of AUD and further supportive to the advancement of new pivotal therapeutic concepts.