Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, postsynaptic density protein 95 (PSD-95), synaptophysin and synapsin, and the activity of Na, K-ATPase (NaK) isoforms in the cerebellum and hippocampus.
View Article and Find Full Text PDFα-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription of the Klotho gene produces two splice variants-a membrane protein (mKl), which can be cleaved and released into the extracellular milieu, and a truncated secreted form (sKl). Despite mounting evidence supporting a role for α-Kl in brain function, the specific roles of α-Kl isoforms in neuronal development remain elusive.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is the leading cause of accident-related death and disability in the world and can lead to long-term neuropsychiatric symptoms, such as a decline in cognitive function and neurodegeneration. TBI includes primary and secondary injury, with head trauma and deformation of the brain caused by the physical force of the impact as primary injury, and cellular and molecular cascades that lead to cell death as secondary injury. Currently, there is no treatment for TBI-induced cell damage and neural circuit dysfunction in the brain, and thus, it is important to understand the underlying cellular mechanisms that lead to cell damage.
View Article and Find Full Text PDF: Interaction of neurons with their extracellular environment and the mechanical forces at focal adhesions and synaptic junctions play important roles in neuronal development. : To advance studies of mechanotransduction, we demonstrate the use of the vinculin tension sensor (VinTS) in primary cultures of cortical neurons. VinTS consists of TS module (TSMod), a Förster resonance energy transfer (FRET)-based tension sensor, inserted between vinculin's head and tail.
View Article and Find Full Text PDFAmyloid-β peptide (Aβ) has been shown to cause synaptic dysfunction and can render neurons vulnerable to excitotoxicity and oxidative stress. Na,K-ATPase plays an important role to maintain cell ionic equilibrium and it can be modulated by N-methyl-D-aspartate (NMDA)-nitric oxide (NO)-cyclic GMP pathway. Disruption of NO synthase (NOS) activity and reactive oxygen species (ROS) production could lead to changes in Na,K-ATPase isoforms' activities that may be detrimental to the cells.
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