Dissecting Astrocyte Complexity in the Human Striatum: Marker-Based and Ultrastructural Perspectives

In brain tissue, GFAP, a cytoskeletal protein, is commonly used to identify reactive astrocytes, often leaving healthy ones unlabeled. GFAP immunoexpression also differs between brain regions and may not increase in all types of astrocyte responses. Although valuable for highlighting reactive changes, GFAP alone may not reflect the full spectrum of structural alterations, such as process loss or cell shrinkage. Including additional markers, such as ALDH1, can provide access to distinct astrocyte subpopulations and their morphological diversity in human striatal tissue.
This study examined 42 human striatal autopsy samples. Standard histological techniques were used, along with GFAP and ALDH1 immunostaining. Transmission electron microscopy (TEM) was performed on selected samples to examine the ultrastructural characteristics of astrocytes at the subcellular level.
In both the chronic alcohol user and young adult groups, more GFAP-positive astrocytes were found in the white matter compared to controls. ALDH1 immunostaining was mainly observed in the gray matter. In the chronic alcohol user group, astrocytes positive for GFAP showed more diverse changes, such as differences in cell body size and altered processes. TEM revealed swollen and vacuolated mitochondria, abundant cytoplasmic vacuoles, and disrupted cytoskeletal organization within astrocytes.
Relying solely on GFAP may not provide a comprehensive view of astrocyte changes, especially in aging. Adding markers, such as ALDH1, allows for more detailed morphological characterization. The changes found in astrocytes, particularly in the alcohol user group, may be linked to blood–brain barrier alterations and white matter damage.