Authors:	Hamed, Salma
Title:	The role of TRPC6 channel in the dentate gyrus and pathophysiology of traumatic brain injury
Online publication date:	22-Jun-2023
Year of first publication:	2023
Language:	english
Abstract:	The TRPC6 channel, a member of the TRP superfamily, is widely expressed in various brain regions, including the dentate gyrus (DG), where its expression is exceptionally high. This research focuses on the significance of TRPC6 in normal hippocampal function and its potential protective role in traumatic brain injury (TBI). The TRPC6 has been shown to play a crucial role in synaptic plasticity processes, including changes in dendritic growth, spine morphology, and an increase in excitatory synapses. Recent evidence suggests that TRPC6 may act as a protective mechanism during ischemic strokes, as its expression is dramatically lessened in neurons following ischemia, leading to neuronal death. The pathological role of TRPC6 in the brain was investigated using a combination of TRPC6 wild-type (WT) and knockout mice (KO), along with various molecular, immunohistology, and electrophysiology techniques. The controlled cortical impact method (CCI) was also used to induce TBI for further study. The research findings demonstrate that deletion of TRPC6 leads to altered hippocampus function, including aberrant maturation of granular cells (GC) in the DG and morphological and electrophysiological modifications, including hypo-excitability and lack of long-term potentiation (LTP). These modifications are accompanied by molecular changes, including alterations in protein phosphorylation and gene expression, which are crucial for synaptic plasticity and neuronal survival, such as CREB, mTOR, and AKT. Additionally, this thesis shows for the first time how deletion of TRPC6 increases the pathogenicity of TBI, manifested as a larger lesion volume. In conclusion, this research sheds light on the critical role of the TRPC6 in maintaining normal brain function and highlights its potential as a target for new approaches in mitigating TBI.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 09 Chemie, Pharmazie u. Geowissensch.
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9110
URN:	urn:nbn:de:hebis:77-openscience-1c92586f-c09a-4756-90fc-2f889380a9ee7
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	http://rightsstatements.org/vocab/InC/1.0/
Extent:	xvii, 144 Seiten ; Illustrationen, Diagramme
Appears in collections:	JGU-Publikationen