Proteomic analysis involved with synaptic plasticity improvement by GABAA receptor blockade in hippocampus of a mouse model of Alzheimer’s disease

• Published in: Neuroscience research Vol. 165; pp. 61 - 68
• Main Authors: Kadoyama, Keiichi, Matsuura, Kenji, Takano, Masaoki, Otani, Mieko, Tomiyama, Takami, Mori, Hiroshi, Matsuyama, Shogo
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2021
• Subjects: Alzheimer’s disease; Bicuculline; Hippocampus; Proteome; Synaptic plasticity; Proteome; Alzheimer’s disease; Hippocampus; Synaptic plasticity; Bicuculline
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2020.04.004

[Display omitted] •Bicuculline improves impaired synaptic plasticity in the dentate gyrus of AD mice.•The expression of 11 proteins is changed for recovering process in the hippocampus.•These proteins play important roles in recovery from impaired synaptic plasticity.•GABAA receptor blockade might contribute to AD cure. GABAergic system plays a part in synaptic plasticity in the hippocampus. We had reported a long-term potentiation (LTP)-like facilitation in vivo, known as synaptic plasticity, through GABAA receptor blockade by bicuculline and the expression of proteins involved with this synaptic plasticity in mouse hippocampus. In the present study, we aimed to show improvement of impaired synaptic plasticity through GABAA receptor blockade and to clarify the molecular mechanisms involved with this improvement in the hippocampus of mice overexpressing human amyloid precursor protein with the E693Δ mutation (APPOSK-Tg) as an Alzheimer’s disease model showing impaired synaptic plasticity. Electrophysiological study showed that the LTP-like facilitation expressed with application of bicuculline in vivo was significantly greater than impaired tetanic LTP in APPOSK-Tg mice, which was improved by bicuculline. Proteomic analysis showed that the expression of 11 proteins in the hippocampus was significantly changed 8 h after bicuculline application to APPOSK-Tg mice. The identified proteins could be functionally classified as chaperone, cytoskeletal protein, energy metabolism, metabolism, neuronal development, and synaptic component. Additionally, western blotting validated the changes in four proteins. We therefore propose that the improvement of impaired synaptic plasticity through GABAA receptor blockade could be mediated by the changed expression of these proteins.