Galectin-9 and Tim-3 are upregulated in response to microglial activation induced by the peptide Amyloid-β (25–35)

Galectins are a group of β-galactoside-binding lectins associated with regulating immunological response. In the brains of AD patients and 5xFAD (familial AD) mice, galectin-3 (Gal-3) was highly upregulated and found to be expressed in microglia associated with Aβ plaques. However, the participation of other galectins, specifically galectin-9 (Gal-9) and T-cell immunoglobulin and mucin domain 3 (Tim-3) receptors, are unknown in the inflammatory response. The experimental model of the Aβ_25–35 peptide will allow us to study the mechanisms of neuroinflammation and describe the changes in the expression of the Gal-9 and Tim-3 receptor. This study aimed to evaluate whether Aβ_25–35 peptide administration into the lateral ventricles of rats upregulated Gal-9 and Tim-3 implicated in the modulation of neuroinflammation. The vehicle or Aβ_25–35 peptide (1 μg/μL) was bilaterally administered into the lateral ventricles of the rat, and control group. After the administration of the Aβ_25–35 peptide, animals were tested for learning (day 29) and spatial memory (day 30) in the novel object recognition test (NOR). On day 31, hippocampus was examined for morphological changes by Nilss stain, biochemical changes by NO₂ and MDA, immunohistochemical analysis by astrocytes (GFAP), microglia (Iba1), Gal-9 and Tim-3, and western blot. Our results show the administration of the Aβ_25–35 peptide into the lateral ventricles of rats induce memory impairment in the NOR by increases the oxidative stress and inflammatory response. This result is associated with an upregulation of Gal-9 and Tim-3 predominantly detected in the microglia cells of Aβ_25–35-treated rats with respect to the control group. Gal-9 and Tim-3 are upregulated in activated microglia that could modulate the inflammatory response and damage in neurodegenerative processes induced by the Aβ_25–35 peptide. Therefore, we suggest that Gal-9 and Tim-3 participate in the inflammatory process induced by the administration of the Aβ_25–35 peptide.