Wang, Mengmeng
(2024)
The Role Of Vacuole Membrane
Protein-1 In Neural Calcium
Homeostasis And Synaptic Plasticity.
PhD thesis, Universiti Sains Malaysia.
Abstract
Disruption of the intracellular calcium (Ca2+) dynamics is previously known to
affect synaptic plasticity and cognitive function. To date, the effects of vacuole
membrane protein 1 (VMP1) on neuronal intracellular calcium homeostasis, synaptic
plasticity, and cognitive function remain unexplored. This study aimed to examine the
effects of VMP1 on neuronal calcium regulation in vitro and in vivo, and its
relationship with synaptic plasticity and cognitive function in vivo. VMP1 expression
was knocked down in SH-SY5Y neuroblastoma cells and the effects on store-operated
calcium entry (SOCE) and calcium channels were assessed using western blot. The in
vivo gain-and-loss function of hippocampal VMP1 was achieved in C57/BL6 mice
using the adeno-associated virus. The effects of VMP1 overexpression and
downregulation on calcium channels, animal cognitive functions, long-term
potentiation (LTP), neuron dendritic spine density, and synaptic-related proteins were
evaluated. In vitro study showed that VMP1 knockdown reduced SOCE (p<0.0001),
transient receptor potential canonical (TRPC1), and calcium release-activated calcium
channel protein 1 (Orai1) in the SH-SY5Y neuroblastoma cells (n=4, P<0.01).
Hippocampal VMP1 knockdown in mice led to decreased TRPC1 expression (n=4,
P<0.01).
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