The Restoration After Repetitive Transcranial Magnetic Stimulation Treatment on Cognitive Ability of Vascular Dementia Rats and Its Impacts on Synaptic Plasticity in Hippocampal CA1 Area

Abstract

The purposes of this research were to study the restoration on the cognitive ability of rat models with vascular dementia (VaD) by repetitive transcranial magnetic stimulation (rTMS) treatment and its impacts on synaptic plasticity in hippocampal CA1 area and to further explore the molecular mechanisms of the rTMS treatment on vascular dementia. Thirty-six male Wistar rats were randomly divided into four groups: the normal control group, the vascular dementia model group, the low-frequency rTMS group, and the high-frequency rTMS group. Two-vessel occlusion was employed to make VaD models. Low-frequency rTMS group rats were treated with 0.5 Hz rTMS for 6 weeks. High-frequency rTMS group rats underwent 5 Hz rTMS for 6 weeks. Morris water maze was carried out to detect the ability of spatial learning and memory of rats. The ultra-structural changes of synapses in four groups were observed by transmission electron microscope. Then the expressions of brain-derived neurotrophic factor (BDNF), NMDAR1, and Synaptophysin (SYN) mRNA and proteins in hippocampal CA1 area were determined by real-time PCR, western blot, and immunohistochemistry assay. After rTMS treatment, the learning and memory abilities of VaD rats improved significantly. The ultra-structures of synapses in hippocampal CA1 area in rTMS groups were reformed. The mRNA and protein expressions of BDNF, NMDAR1, and SYN in the low-frequency rTMS group and in the high-frequency rTMS group were higher than that in VaD model group (P < 0.05). rTMS plays an important and beneficial role in the restoration treatment of vascular dementia, which may be related to the mechanism that rTMS can increase the mRNA and protein expressions of BDNF, NMDAR1, and SYN and affect the synaptic plasticity in hippocampal CA1 area.

A Review of Transcranial Magnetic Stimulation in Vascular Dementia

“…A recent study of rTMS in rat models of VaD has reported an improvement of both learning and memory abilities after the administration of low-frequency or high-frequency stimuli. As suggested by the authors, the restoration of cognitive functions could be the result of the biological effects of rTMS that probably acts by promoting the expression of brain-derived neurotrophic factor and other proteins, such as NMDAR1 and synaptophysin, involved in neuronal cell protection, synaptic transmission and brain plasticity [113]. …”

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

“…A human study confirmed that after‐effects of rTMS (theta burst stimulation) are linked to the function of the NMDAR 44. Moreover, animal and behavioral studies45, 46, 47, 48, 49 provide compelling evidence that rTMS alters synaptic plasticity of hippocampal areas. Thus, rTMS may be used in order to improve hippocampal function and increase neuronal NMDAR expression.…”

“…There is evidence from animal models that rTMS may increase the mRNA and protein expression of NMDAR 43. A human study confirmed that after‐effects of rTMS (theta burst stimulation) are linked to the function of the NMDAR 44.…”

The Role of Hippocampal Structural Synaptic Plasticity in Repetitive Transcranial Magnetic Stimulation to Improve Cognitive Function in Male SAMP8 Mice

“…rTMS at appropriate frequency, intensity, and duration may alter the expression of neurotrophins and their receptors [12, 23, 29, 30], neurotransmitters and their receptors [14, 30-32], and structural proteins [12, 23] in synapses, which in turn affects the postsynaptic depolarization, inducing LTP or LTD and contributing to different cognitive functions.…”