RT Journal Article
SR Electronic
T1 Low-Level Laser Therapy Rescues Dendrite Atrophy via Upregulating BDNF Expression: Implications for Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13505
OP 13517
DO 10.1523/JNEUROSCI.0918-13.2013
VO 33
IS 33
A1 Meng, Chengbo
A1 He, Zhiyong
A1 Xing, Da
YR 2013
UL http://www.jneurosci.org/content/33/33/13505.abstract
AB Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via upregulation of BDNF in both Aβ-treated hippocampal neurons and cultured APP/PS1 mouse hippocampal neurons. Photoactivation of transcription factor CRE-binding protein (CREB) increased both BDNF mRNA and protein expression, since knockdown CREB blocked the effects of LLLT. Furthermore, CREB-regulated transcription was in an ERK-dependent manner. Inhibition of ERK attenuated the DNA-binding efficiency of CREB to BDNF promoter. In addition, dendrite growth was improved after LLLT, characterized by upregulation of Rac1 activity and PSD-95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT by activation of ERK/CREB pathway can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of AD.