Knockdown of Follistatin-like 1 disrupts synaptic transmission in hippocampus and leads to cognitive impairments
| Autor: | Yuying Zhang, Tianyue Jiang, Ziying Ke, Yingchun Shang, Zhuo Yang, Wen Ning, Tao Zhang, Shitong Xiang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Nervous system Follistatin-Related Proteins Patch-Clamp Techniques Hippocampus Gene Expression Glutamic Acid Biology Neurotransmission Synaptic Transmission 03 medical and health sciences Glutamatergic Mice 0302 clinical medicine Developmental Neuroscience Memory medicine Animals Learning Cognitive Dysfunction gamma-Aminobutyric Acid Mice Knockout Gene knockdown Neuronal Plasticity Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neurology Synaptic plasticity Neuron Neurotransmitter transport Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology. 333 |
| ISSN: | 1090-2430 |
| Popis: | Follistatin-like 1 (FSTL1), also named transforming growth factor (TGF)-β1-inducible gene, is a secreted extracellular glycoprotein expressing widely in nervous system. Several recent studies have revealed that FSTL1 plays an essential role in neurological diseases including neuropathic pain and ischemic stroke. It proves that FSTL1 suppresses synaptic transmission by activating Na/K-ATPase in DRG neurons and inhibits neuronal apoptosis by phosphorylation AKT signaling. However, it is not clear whether FSTL1 can play a role in other type of neuron or neurodegenerative diseases. 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. |
| Databáze: | OpenAIRE |
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