Aim
To elucidate the molecular mechanism underlying the repetitive transcranial magnetic stimulation (rTMS) -induced improvement in Parkinson's disease (PD). Material and
Conclusion
rTMS exerted its neuroprotective effects on PD mice by regulating the miR-195a-5p/CREB axis. This finding reveals a novel mechanism through which rTMS improves PD and indicates that miR-195a-5p is a potential therapeutic target for PD treatment.
Material and methods
We established a PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to SAMP8 mice. The mice were then subjected to rTMS. Motor coordination and cognition were assessed using rotarod and Morris water maze tests, respectively. Nissl staining was performed to evaluate neuronal apoptosis. Furthermore, western blotting was employed to assess the expression of tyrosine hydroxylase and brain-derived neurotrophic factor. Additionally, the levels of tumor necrosis factor-α, interferon-γ, and interleukin-6 in the cerebrospinal fluid were evaluated using specific enzyme-linked immunosorbent assay kits. The expression of miR-195a-5p and cyclic AMP-response element-binding protein (CREB) was examined using quantitative real-time polymerase chain reaction and western blotting. Dual-luciferase reporter assay was performed using primary cortical rat neurons to validate the interaction between miR-195a-5p and CREB.
Methods
We established a PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to SAMP8 mice. The mice were then subjected to rTMS. Motor coordination and cognition were assessed using rotarod and Morris water maze tests, respectively. Nissl staining was performed to evaluate neuronal apoptosis. Furthermore, western blotting was employed to assess the expression of tyrosine hydroxylase and brain-derived neurotrophic factor. Additionally, the levels of tumor necrosis factor-α, interferon-γ, and interleukin-6 in the cerebrospinal fluid were evaluated using specific enzyme-linked immunosorbent assay kits. The expression of miR-195a-5p and cyclic AMP-response element-binding protein (CREB) was examined using quantitative real-time polymerase chain reaction and western blotting. Dual-luciferase reporter assay was performed using primary cortical rat neurons to validate the interaction between miR-195a-5p and CREB.
Results
rTMS improved cognition and motor coordination as well as reduced neuronal apoptosis/ and the levels of inflammatory factors in PD mice. It downregulated the expression of miR-195a-5p but upregulated that of CREB. In primary rat cortical neurons, miR-195a-5p directly targeted CREB, and we found that miR-195a-5p suppression enhanced cognitive and motor functions in PD mice. Moreover, miR-195a-5p downregulation decreased inflammatory response and neuronal loss in the PD mice.