A Comparative Analysis of Microglial and Astrocyte Transplantation in an Amyloid-Induced Rat for Alzheimer’s Disease

Alzheimer’s disease (AD) is recognized as a neuroglial disorder in which dysregulated glial responses contribute to cognitive decline. We investigated whether intrahippocampal transplantation of primary glial cells modifies cognitive trajectories in an amyloid-induced rat model of AD. Sprague–Dawley rats received bilateral hippocampal injections of pre-aggregated Aβ₁–₄₂, followed by transplantation of primary astrocytes (AA) or microglia (AM). Memory was assessed using the Y-maze and novel object recognition (NOR) tests. Body weight and serum IL-6 and TNF-α were monitored for adverse effects, and GFAP, S100, Iba1 and TREM2 immunolabeling was quantified with QuPath. Mixed-effects models showed significant session and group x session effects on Y–maze spatial novelty recognition. Both treated groups improved compared with AD animals, with a stronger late effect in the AM group and a significant group × session × sex interaction. In the NOR test, both treated groups outperformed AD animals at the final session, without differences between them. GFAP (glial fibrillary acidic protein) immunoreactivity was reduced in the AM group but remained elevated in the AA group, while TREM2 increased after microglial and decreased after astrocyte transplantation. No adverse effects were detected in the monitored parameters. Intrahippocampal glial transplantation, particularly with microglia, may influence cognitive trajectories in established amyloid pathology.