Pre- and post-treatment of α-Tocopherol on cognitive, synaptic plasticity, and mitochondrial disorders of the hippocampus in icv-streptozotocin-induced sporadic Alzheimer’s-like disease in male Wistar rat

Abstract

ObjectiveMost dementia cases in the elderly are caused by Alzheimer’s disease (AD), a complex, progressive neurological disease. Intracerebroventricular (ICV) administration of streptozotocin (STZ) in rat’s results in aberrant brain insulin signaling, oxidative stress, and mitochondrial dysfunction that impair cognition change neural plasticity, and eventually lead to neuronal death. The current study aims to define the neuroprotective action of alpha-tocopherol in enhancing mitochondrial function and the function of synapses in memory-impaired rats brought on by icv-STZ.MethodsMale Wistar rats were pre-treated with (α-Tocopherol 150 mg/kg) orally once daily for 7 days before and 14 days after being bilaterally injected with icv-STZ (3 mg/kg), while sham group rats received the same volume of STZ solvent. After 2 weeks of icv-STZ infusion, rats were tested for cognitive performance using a behaviors test and then were prepared electrophysiology recordings or sacrificed for biochemical and histopathological assays.ResultsThe cognitive impairment was significantly minimized in the behavioral paradigms for those who had taken α-Tocopherol. In the hippocampus of icv-STZ rat brains, α-Tocopherol ocopherol effectively prevented the loss of glutathione levels and superoxide dismutase enzyme activity, lowered mitochondrial ROS and mitochondrial membrane potential, and also brought about a decrease in Aβ aggregation and neuronal death.ConclusionOur findings demonstrated that by lowering neurobehavioral impairments caused by icv-STZ, oxidative stress, and mitochondrial dysfunction, α-Tocopherol enhanced intracellular calcium homeostasis and corrected neurodegenerative defects in the brain. These findings examine the available approach for delaying AD connected to mitochondrial malfunction and plasticity issues.

The 40 Hz flickering light restores synaptic plasticity and mitochondrial phenotype in experimental model of Alzheimer’s disease

“…Neuronal plasticity is directly related to greater synaptic efficacy achieved through longterm potentiation (LTP). In animals, LTP is the long-term modification in synaptic strength induced by electrical stimulation which is used in AD research studies [48,74]. To further investigate the long-term effects of flickering 40 Hz light and bilateral injection of STZ into the hippocampus on neuronal activity, we assessed basal synaptic transmission and plasticity in perforant hippocampi one month after injection.…”

“…Following the tetanic stimuli, the baseline stimulation was resumed, and the recording was carried out for at least 60 minutes. The average of five successive evoked responses was taken at intervals of 10 seconds [48].…”

“…Ten consecutive evoked responses were averaged for each paired-pulse stimulation. Various interstimulus intervals were used to determine the fEPSP slope ratio [percentage of the second fEPSP slope/first fEPSP slope; fEPSP2/fEPSP1%] and the population spike amplitude ratio [percentage of the second population spike amplitude to the first population spike amplitude; PS2/PS1%] [48].…”

Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults

“…The baseline stimulation was restarted after the tetanic stimuli, and the recording continued for at least 60 min. Five consecutive evoked responses were averaged at 10-second intervals ( Nabavi Zadeh et al, 2023 ).…”

“…Ten consecutive evoked responses were averaged for each of them. The fEPSP slope ratio [percentage of the second fEPSP slope to the first fEPSP slope; fEPSP2/fEPSP1%] and the population spike amplitude ratio [percentage of the second population spike amplitude to the first population spike amplitude; PS2/PS1%] were determined using various interstimulus intervals ( Nabavi Zadeh et al, 2023 ).…”