Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway

Abstract

Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca] level, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca) stores. Blockade of Ca increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.

Low‐level laser therapy 810‐nm up‐regulates macrophage secretion of neurotrophic factors via PKA‐CREB and promotes neuronal axon regeneration in vitro

“…At the same time, studies have revealed that LLLT can also promote the secretion of neurotrophic factors. Yan et al showed that LLLT can increase the phosphorylation level of CREB by increasing the expression of ERK in dorsal root ganglia, which in turn promoted the levels of neuronal neurotrophic factors. However, the exact mechanism by which LLLT improves the secretion of neurotrophic factors in M1 macrophages remains to be elucidated.…”

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

“…Specifically, it is believed to modulate dendritic structure to facilitate improved synaptic transmission [121]. PBM has been shown to slow attenuation of BDNF via the ERK/CREB pathway, thus positively affecting dendritic morphogenesis and improved neuronal connectivity [122]. BDNF is also a mediator of the protein synapsin-1, which improves synaptogenesis by accelerating the development of neuronal fibers and maintaining synaptic contacts [123].…”

Brain Photobiomodulation Therapy: a Narrative Review

“…PBM therapy increases cerebral blood flow (CBF) [17–19], augments brain energy metabolism [17,20,21] and increases antioxidant defenses [20]. Moreover, its ability to promote neuronal protection and survival is mediated through modulation of anti-apoptotic and pro-apoptotic mediators [22,23] and inflammatory signaling molecules [24,25] as well as the stimulation of neurotrophic factors [4,26,27]. Besides these therapeutic effects at the molecular level, there is also considerable evidence of changes occurring at the behavioral level such as cognitive-enhancement, antidepressant effects and improved sleep [7,28–30].…”