White and Gray Matter Alterations in the Human Striatum: Astrocytic and Neuronal Perspectives on Neurodegeneration

Astrocytes are essential contributors to the functionality of the central nervous system, acting as dynamic safeguards by maintaining tissue homeostasis and supporting neuronal health. Their density and activity adapt to pathological conditions, such as those caused by chronic alcohol consumption, leading to the disruption of neuronal integrity. While increased astrocyte density is a well-documented response to injury and inflammation, its manifestation in the striatum, a region central to motor control and reward processing, remains less explored. This study aims to provide insights into the regional specificity of astrocytic changes by evaluating the distribution of GFAP-immunopositive astrocytes in the striatal gray matter (GM) and white matter (WM), with an emphasis on the interplay between astrocytes and neurons in this key area.
Formalin-fixed and paraffin-embedded human brain tissue samples were obtained from the Latvian State Centre for Forensic Medical Examination, processed using standard histopathology methods, and analyzed using cytoskeletal protein GFAP immunohistochemistry. The study included 42 striatal autopsy samples, which were divided into young alcohol (YA) users (n=10; mean age 30), chronic alcohol (CA) users (n=20; mean age 55), and controls (n=12; mean age 30). Blood ethanol concentrations ranged from 0.59% to 4.61% in age-matched alcohol users and from 1.07% to 3.58% in chronic alcohol users.
Significantly more GFAP-positive astrocytes were detected in the WM of both the CA and YA groups compared to controls. Additionally, both CA and YA groups showed a statistically significant decrease in neuronal numbers compared to controls. However, in the GM, no significant differences were found in the total number of GFAP-positive astrocytes across study groups. In alcohol user groups, astrocytes exhibited morphological changes, including variations in nuclear size, soma size, and the number of processes.
Alcohol use significantly reduces the number of neurons in the striatum, underscoring the vulnerability of this region to alcohol's neurotoxic effects. Although the overall number of GFAP-positive astrocytes did not differ between groups in the GM, their increased density in the WM highlights regional specificity in cellular responses to alcohol dependence. Chronic alcohol use was associated with microstructural and cytoskeletal abnormalities in astrocytes, particularly in the WM, which may have affected their functionality and role in maintaining axonal integrity. These findings further support evidence of WM volume shrinkage due to alcohol consumption, even in young alcohol users.