| First Author | Matsuo K | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 1 | PubMed ID | 33401521 |
| Mgi Jnum | J:305658 | Mgi Id | MGI:6705860 |
| Doi | 10.3390/ijms22010400 | Citation | Matsuo K, et al. (2021) Crucial Role of FABP3 in alphaSyn-Induced Reduction of Septal GABAergic Neurons and Cognitive Decline in Mice. Int J Mol Sci 22(1):400 |
| abstractText | In synucleinopathies, while motor symptoms are thought to be attributed to the accumulation of misfolded alpha-synuclein (alphaSyn) in nigral dopaminergic neurons, it remains to be elucidated how cognitive decline arises. Here, we investigated the effects of distinct alphaSyn strains on cognition and the related neuropathology in the medial septum/diagonal band (MS/DB), a key region for cognitive processing. Bilateral injection of alphaSyn fibrils into the dorsal striatum potently impaired cognition in mice. The cognitive decline was accompanied by accumulation of phosphorylated alphaSyn at Ser129 and reduction of gamma-aminobutyric acid (GABA)-ergic but not cholinergic neurons in the MS/DB. Since we have demonstrated that fatty acid-binding protein 3 (FABP3) is critical for alphaSyn neurotoxicity in nigral dopaminergic neurons, we investigated whether FABP3 also participates in alphaSyn pathology in the MS/DB and cognitive decline. FABP3 was highly expressed in GABAergic but rarely in cholinergic neurons in the MS/DB. Notably, Fabp3 deletion antagonized the accumulation of phosphorylated alphaSyn, decrease in GABAergic neurons, and cognitive impairment caused by alphaSyn fibrils. Overall, the present study indicates that FABP3 mediates alphaSyn neurotoxicity in septal GABAergic neurons and the resultant cognitive impairment, and that FABP3 in this subpopulation could be a therapeutic target for dementia in synucleinopathies. |
