Photobiomodulation upregulates neuroligin-3 and improves the synapses and cognitive function and ameliorates epileptic seizure

Author:

Hong Namgue1,Kim Hee Jung1,Kang Keunsoo2,Kim Hyung-Gun1,Kang Bong Hui3,Chung Phil-Sang1,Lee Min Young3ORCID,Ahn Jin-Chul1

Affiliation:

1. Dankook University College of Medicine

2. Dankook University

3. Dankook University Hospital

Abstract

Abstract Background Temporal 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. Methods In 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, histological stain and immunohistochemistry analyses were used to assess neuronal survival, synaptic connections and neuroinflammation. Behavioral tests were used to evaluate the effects of PBM on cognitive functions. RNA sequencing was performed to identify the gene regulatory by PBM. Results PBM was upregulated synaptic connections in an in vitro. In addition, it was confirmed that transcranial PBM reduced neuronal apoptosis, synaptic degeneration, 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 robust 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. Conclusions Our findings demonstrate that PBM attenuates epileptic excitotoxicity, neurodegeneration and cognitive decline induced by TLE through gene regulation of the neuronal developments including Nlgn3.

Publisher

Research Square Platform LLC

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