rTMS alleviates AD-induced cognitive impairment by inhibitng apoptosis in SAMP8 mouse

Abstract

This study sought to investigate whether repetitive transcranial magnetic stimulation (rTMS) could alleviate cognitive dysfunction in SAMP8 mice by reducing cell apoptosis and activating the cAMP/PKA/CREB signalling pathway. A total of 40 SAMP8 mice were randomly assigned to the SAMP8 group (n=20), and rTMS treatment group (rTMS+SAMP8, n=20); additionally, 20 homologous and normal aged SAMR1 mice were used as the control group(n=20). The Morris water maze and Y maze tests were applied to evaluate spatial learning and memory ability. Haematoxylin and eosin (HE) staining and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) were used to observe the changes in neurons in the cortex and hippocampus. Western blotting and RT-PCR were used to detect signalling related proteins. rTMS significantly improved spatial learning and memory deficits and morphological abnormalities in the hippocampus region of the hippocampus. In addition, rTMS reduced apoptosis of neurons caused by AD and the expression of pro-apoptotic proteins (Caspase-3 and Bax) and increased the expression of an antiapoptotic protein (Bcl-2). Furthermore, rTMS activated the cAMP/PKA/CREB signalling pathway. These results showed that rTMS could ameliorate cognitive deficits in AD mice by inhibiting apoptosis via activation the cAMP/PKA/CREB signalling pathway.

High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China

“…The similar performance was observed in our study and just showed a positive change in response to rTMS treatment. Animal studies on mice reported that rTMS were able to ameliorate cognitive deficits due to AD and improve memory ability by changing the electrophysiological properties of the hippocampus and increasing neuronal excitability 28 . rTMS may be a promising useful tool as single or combined therapy for individuals with memory decline due to MCI and AD.…”

Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms

“…112,113 Accumulating studies show that rTMS could modulate neural apoptosis in the brain of patients with AD. 85,107,114 We previously found that a 1-month iTBS treatment reduces caspase-3 and Bax levels and increases the expression of Bcl-2, and therefore, suppresses the number of TUNEL-positive cells in the hippocampus of APP/PS1 mice, suggesting the antiapoptotic effects of rTMS in AD. 85,102 Consistent with our findings, previous studies also indicated that rTMS inhibited neuronal apoptosis in other animal models such as 3xTg-AD mice 107 and trimethyltin (TMT)-induced Alzheimer's-like rat models, 115 in which the rTMS-induced antiapoptotic effects, that were related to the modulation of PI3K/Akt/ GLT-1 or PI3K/Akt/mTOR signaling pathways.…”

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“…These neurotransmitters are pivotal in excitatory and inhibitory synaptic transmission, influencing cellular responses and network activity. cAMP and PKA signaling: TMS-induced neuronal depolarization can activate cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) signaling pathways [ 77 ]. These pathways are involved in intracellular signal transduction and modulation of gene expression.…”