Knockdown of Follistatin-like 1 disrupts synaptic transmission in hippocampus and leads to cognitive impairments.

In this study, we found that the mice with Fstl1 genetic knockdown showed not only the impairments of learning and memory abilities, but also abnormal neural oscillations and synaptic plasticity in the hippocampus. Subsequently, we identified broad transcriptional changes including 55 up-regulated and 184 down-regulated genes in Fstl1 knockdown mice by RNA-Seq analysis, as well as neurotransmitter transport, synaptic transmission and disease-related genes. The expression changes of some DEGs were further validated via quantitative Realtime PCR (qRT-PCR). Further patch-clamp whole cell recording showed that Fstl1+/- mice displayed a significant decrease in glutamatergic synaptic transmission and increase in GABAergic synaptic transmission, which were consistent with the RNA-Seq analysis. Taken together, our results provide an evidence and a possibly underlying mechanism for the critical role of FSTL1 in the hippocampus on learning and memory and normal neural oscillations, suggesting that FSTL1 may plays an important role in neurodegenerative diseases related to cognitive impairments. PMID: 32721453 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research