Delayed Expression of Both GABA B R1 and GABA B R2 Subunits in Murine Hippocampal Dentate Gyrus After a Single Systemic Injection of Trimethyltin

• Published in: Neurochemical research 2022-09, Vol.47 (9), p.2780
• Main Authors: Onishi, Yuki, Yamamura, Yusuke, Hosogi, Misa, Higashi, Hiroshi, Ogita, Kiyokazu, Kinjo, Toshihiko, Uno, Kyosuke, Yoneda, Yukio, Kuramoto, Nobuyuki
• Format: Article
• Language: English
• Subjects: Animals; Dentate Gyrus - metabolism; gamma-Aminobutyric Acid - metabolism; Hippocampus - metabolism; Mammals; Mice; Receptors, GABA-B; Trimethyltin Compounds - toxicity
• ISSN: 1573-6903
• DOI: 10.1007/s11064-022-03652-7

Trimethyltin (TMT) has been used as a cytotoxin to neurons rather than glial cells in the mammalian hippocampus. The systemic administration of TMT led to declined fluorescence of ZnAF-2 DA staining as a marker of intact mossy fibers and increased fluorescence of Fluoro-Jade B staining as a marker of degenerated neurons during the initial 2 to 5 days after the administration with later ameliorations within 30 days in the hippocampal dentate gyrus (DG) and CA3 region in mice. On immunoblotting analysis, both GABA R1 and GABA R2 subunit levels increased during 15 to 30 days after TMT along with significant decreases in glutamatergic GluA1 and GluA2/3 receptor subunit levels during 2 to 7 days in the DG, but not in other hippocampal regions such as CA1 and CA3 regions. Immunohistochemical analysis revealed the constitutive and inducible expression of GABA R2 subunit in cells immunoreactive to an astrocytic marker as well as neuronal markers in the DG with the absence of neither GABA R1a nor GABA R1b subunit from cells positive to an astrocytic marker. These results suggest that both GABA R1 and GABA R2 subunits may be up-regulated in cells other than neurons and astroglia in the DG at a late stage of TMT intoxication in mice.