Simvastatin ameliorates cognitive impairments via inhibition of oxidative stress‑induced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia

Abstract

Senile dementia is a degenerative disease of the nervous system associated with cognitive impairments, memory disorders, executive dysfunctions, cognitive decline and dementia. Previous reports suggested that simvastatin presents ameliorative effects in the progression of senile dementia. However, the mechanism underlying simvastatin‑mediated improvements of cognitive competence during the progression of senile dementia remains to be elucidated. In the present study, a potential mechanism underlying simvastatin activity in hippocampal cells, was investigated. Results of the present study demonstrated that simvastatin significantly improved cognitive impairments, memory competence, amyloid plaques, loss of neurons and synapses, neurofibrillary tangles and oxidative damage in experimental rats. Results of the present study demonstrated that administration of simvastatin regulates superoxide dismutase, reactive oxygen species, catalase and glutathione in oxidative stress processes in hippocampal cells. Apoptosis of hippocampal cells was suppressed by simvastatin treatment in rats with senile dementia. Notably, the administration of simvastatin inhibited activating transcription factor‑6‑mediated extracellular signal‑regulated kinase/AKT serine/threonine kinase (ERK/AKT) signaling pathway in hippocampal cells. Taken together, the preclinical results of the present study indicate that simvastatin is efficient in preventing memory lapse and inhibiting apoptosis of hippocampal cells via the ERK/AKT signaling pathway, which may in the future improve cognitive decline and dementia in patients.

Simvastatin rescues memory and granule cell maturation through the Wnt/β-catenin signaling pathway in a mouse model of Alzheimer’s disease

“…Nevertheless, several pre-clinical studies using statins in animal models of AD strongly support their potential therapeutic value. Particularly relevant are reports of improved or fully restored memory, hippocampal and cerebrovascular function in various AD animal models [ 13 – 19 ]. These benefits occurred without reducing the classic AD biomarker, amyloid-β (Aβ) levels or Aβ plaque load [ 14 , 15 , 20 , 21 ], emphasizing the need to explore therapeutic avenues directed at targets other than the Aβ pathology, as supported by the repeated failure of Aβ-directed approaches throughout the years [ 22 , 23 ].…”

Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype

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Clinical observation of the efficacy and mechanism of the Wenfei Jiangzhuo formula in lung and kidney deficiency-type vascular dementia

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