Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aβ1-42

Abstract

Voltage-gated sodium channel beta 2 (Nav2.2 or Navβ2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navβ2 in amyloid-β 1-42- (Aβ1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navβ2 knockdown restored neuronal viability of Aβ1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aβ42, sAPPα, and sAPPβ, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aβ degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navβ2 plays crucial roles in the repair of neuronal injury induced by Aβ1-42 both in vivo and in vitro.

Ion Channel and Transporter Involvement in Chemotherapy-Induced Peripheral Neurotoxicity

“…The regulation is cell dependent [ 26 ]. Nav 1.3 is upregulated in several pain disorders, and the resulting hyperexcitability may explain its involvement; the fast kinetic that characterizes this channel supports its role in allowing peripheral nerves to fire at high frequencies [ 27 , 28 ].…”

The Role of Genetic Mutation on Schizophrenia: A Basic Review Prior to Pharmacogenomics

“…SCN2B, a gene key in the maintenance of standard physiological processes hippocampus and prefrontal cortex, may be linked to prefrontal cortex ageing the memories impairment [28], while not part of the major network, it was upregulated on the schizophrenia [29]. The sodium-potassium pump set consists of 14 genes, ten of which encode alpha subunits responsible for the formation of action potentials, and four of which together with subunits alpha affect cellular and gating excitability.…”