FSTL1-knockdown improves neural oscillation via decreasing neuronal-inflammation regulating apoptosis in Aβ1-42
Ekta Kumari1, Aoxi Xu2, Runwen Chen1
1College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071 Tianjin, PR China.
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.
Insights
Follistatin like protein 1 (FSTL1) knockdown improved cognitive function in Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Follistatin like protein 1 (FSTL1) is a growth regulatory protein implicated in various diseases.
- FSTL1's role in central nervous system development suggests a potential link to neurological disorders.
- Upregulated FSTL1 expression was observed in Alzheimer's disease (AD) mouse models.
Purpose of the Study:
- To investigate the function and role of FSTL1 in Alzheimer's disease.
- To determine if FSTL1 knockdown can ameliorate AD-like pathology and cognitive deficits.
Main Methods:
- Alzheimer's disease model mice were generated using intracerebroventricular injections of amyloid-beta (Aβ) peptides.
- FSTL1 knockdown was performed in AD model mice (FSTL1+/-) and compared to control (CON) mice.
- Cognitive function, neural oscillations, synaptic plasticity, microglial activation, and apoptosis pathways were assessed.
Main Results:
- FSTL1 knockdown significantly improved cognitive functions in Aβ-induced AD model mice.
- Knockdown enhanced neural oscillations and synaptic plasticity while inhibiting microglial activation and inflammatory responses.
- FSTL1 knockdown modulated the apoptosis pathway (caspase/BAX/Bcl-2/TLR-4) and reduced amyloid-beta burden.
Conclusions:
- Down-regulation of FSTL1 demonstrates clinical significance in mitigating Alzheimer's disease progression.
- FSTL1 knockdown reduces amyloid-beta, neuroinflammation, and apoptosis in an AD-like mouse model.
- Reduced FSTL1 improves synaptic plasticity, neural oscillations, and cognitive behaviors in AD models.
