Microglial voltage-gated sodium channels modulate cellular response in Alzheimer's disease - a new perspective on an old problem

作者：Catalin Bogdan^*; Mitran Smaranda; Ciorbagiu Mihai; Osiac Eugen; Balseanu Tudor Adrian; Mogoanta Laurentiu; Dinescu Sorin Nicolae; Albu Carmen Valeria; Mirea Cecil Sorin; Vilcea Ionica Daniel; Iancau Maria; Sfredel Veronica

来源：Romanian Journal of Morphology and Embryology, 2015, 56(1): 21-25.

• voltage-gated sodium channels
• microglia
• Alzheimer's disease

Alzheimer's disease (AD) determines gradual loss of cognition and memory function, eventually leading to clinical manifest dementia. The pathogenic mechanisms of AD remain elusive and treatment options unsatisfactory, targeting only symptoms like memory loss, behavior changes, sleep disorders and seizures. These therapies are not stopping the disease's progression, at their best they can only delay it. Accumulating evidence suggests that AD is associated with a microglial dysfunction. Microglia are resident immune cells that provide continuous surveillance within the brain. When excessively activated, microglial response can also have detrimental effects via the exacerbation of inflammatory processes and release of neurotoxic substances. Recently, it was recognized that microglia express voltage-gated ion channels, in particularly voltage-gated sodium channels (VGSC). Pharmacological block of VGSC has been attempted symptomatically in AD to control the epileptic features often associated with AD, as well as to relieve detrimental behavioral and psychological symptoms of dementia. The success of VGSC treatment in AD was unexpectedly variable, ranging from very beneficial to plain detrimental. This variability could not be satisfactorily explained solely by the neuronal effects. This article will try to discuss possible implication of microglial VGSC dysfunction in AD according to available data, own personal experience of the authors and propose a new way to investigate its possible implications.

• 出版日期2015