Photobiomodulation improves the synapses and cognitive function and ameliorates epileptic seizure by inhibiting downregulation of Nlgn3

Cell & Bioscience

Research

Phil-Sang Chung¹  Ji On Park²  Keunsoo Kang³  Seyoung Mun⁴  Bong Hui Kang⁵  Hyung-Gun Kim⁶  Hee Jung Kim⁷  Namgue Hong⁸  Jin-Chul Ahn⁹  Min Young Lee^1,10 

[1] Beckman Laser Institute Korea, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;Department of Medicine, Graduate School of Dankook University, Dankook University, Cheonan, Republic of Korea;Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, Republic of Korea;Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, Republic of Korea;Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, Republic of Korea;Department of Neurology, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;Department of Pharmacology, College of Medicine, Dankook University, Cheonan, Republic of Korea;Department of Physiology, College of Medicine, Dankook University, Cheonan, Republic of Korea;Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea;Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, Republic of Korea;Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea;Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, Republic of Korea;Beckman Laser Institute Korea, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea;Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, Republic of Korea;Beckman Laser Institute Korea, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University Hospital, Dankook University, Cheonan, Republic of Korea;

关键词: Temporal lobe epilepsy;    Excitotoxicity;    Near infrared light;    Synapse;    Neuroligin-3;   

DOI  :  10.1186/s13578-022-00949-6

 received in 2022-09-07, accepted in 2022-12-21,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundTemporal lobe epilepsy (TLE) remains one of the most drug-resistant focal epilepsies. Glutamate excitotoxicity and neuroinflammation which leads to loss of synaptic proteins and neuronal death appear to represent a pathogen that characterizes the neurobiology of TLE. Photobiomodulation (PBM) is a rapidly growing therapy for the attenuation of neuronal degeneration harboring non-invasiveness benefits. However, the detailed effects of PBM on excitotoxicity or neuroinflammation remain unclear. We investigated whether tPBM exerts neuroprotective effects on hippocampal neurons in epilepsy mouse model by regulating synapse and synapse-related genes.MethodsIn an in vitro study, we performed imaging analysis and western blot in primary hippocampal neurons from embryonic (E17) rat pups. In an in vivo study, RNA sequencing was performed to identify the gene regulatory by PBM. Histological stain and immunohistochemistry analyses were used to assess synaptic connections, neuroinflammation and neuronal survival. Behavioral tests were used to evaluate the effects of PBM on cognitive functions.ResultsPBM was upregulated synaptic connections in an in vitro. In addition, it was confirmed that transcranial PBM reduced synaptic degeneration, neuronal apoptosis, and neuroinflammation in an in vivo. These effects of PBM were supported by RNA sequencing results showing the relation of PBM with gene regulatory networks of neuronal functions. Specifically, Nlgn3 showed increase after PBM and silencing the Nlgn3 reversed the positive effect of PBM in in vitro. Lastly, behavioral alterations including hypoactivity, anxiety and impaired memory were recovered along with the reduction of seizure score in PBM-treated mice.ConclusionsOur findings demonstrate that PBM attenuates epileptic excitotoxicity, neurodegeneration and cognitive decline induced by TLE through inhibition of the Nlgn3 gene decrease induced by excitotoxicity.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2022

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