FSTL1-knockdown improves neural oscillation via decreasing neuronal-inflammation regulating apoptosis in Aβ1–42 induced AD model mice

Abstract

Follistatin like protein 1 (FSTL1) is a famous growth regulatory protein. FSTL1 has been noticed in many diseases, including heart and lung ischemia, cerebral ischemia, glioma, schizophrenia, and Autism. The role of FSTL1 has been declared in the genetics and development of the central nervous system. Therefore, we designed this study to investigate the function and the role of FSTL1 in Alzheimer's disease. Firstly, we noticed upregulated expression level of FSTL1 among four to six-month-old 5XFAD AD mice. Accordingly, we hypothesized that FSTL1-Knockdown improved AD model mice's cognitive function and recover from Alzheimer's disease. Thus, AD model mice were made by single intracerebroventricular injections of Aβ1–42 peptides in FSTL1+/− and CON mice. Next, our results concluded that FSTL1-knockdown effectively improved cognitive functions. FSTL1-knockdown enhanced the pattern of neural oscillations, and synaptic plasticity in Aβ1–42 treated FSTL1-Knockdown mice compared to Aβ1–42 induced AD model mice. Next, FSTL1-Knockdown inhibited the activation of microglia and binding of TLR-4 with microglia. Further, inactivated microglia stopped the formation of MyD88. Thus, our data revealed that FSTL1-Knockdown is slowing down the caspase/BAX/Bcl-2/TLR-4 regulating apoptosis pathway, and the expression of inflammatory cytokines in the hippocampus of Aβ1–42 inserted FSTL1-Knockdown mice. Overall, all these data illuminate the clinical significance role of down-regulated FSTL1. FSTL1-Knockdown reduced the amyloid-beta by affecting microglia, neural-inflammation and apoptosis in AD-like model mice. Finally, down regulation of FSTL1 improved synaptic plasticity, neural oscillations, and cognitive behaviours in the Aβ1–42 induced AD model mice.