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Neuroprotective Effects of Metformin Against Aβ-Mediated Inhibition of Long-Term Potentiation in Rats Fed a High-Fat Diet Publisher Pubmed



Asadbegi M1 ; Yaghmaei P1 ; Salehi I2 ; Ebrahimhabibi A3, 4 ; Komaki A2, 5
Authors
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Authors Affiliations
  1. 1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  2. 2. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
  3. 3. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Departement of Physiology, School of Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran

Source: Brain Research Bulletin Published:2016


Abstract

Metformin (Met) is used to treat neurodegenerative disorders such as Alzheimer's disease (AD). Conversely, high-fat diets (HFD) have been shown to increase AD risk. In this study, we investigated the neuroprotective effects of Met on β-amyloid (Aβ)-induced impairments in hippocampal synaptic plasticity in AD model rats that were fed a HFD. In this study, 32 adult male Wistar rats were randomly assigned to four groups: group I (control group, regular diet); group II (HFD + vehicle); group III (HFD + Aβ); or group IV (Met + HFD + Aβ). Rats fed a HFD were injected with Aβ to induce AD, allowed to recover, and treated with Met for 8 weeks. The rats were then anesthetized with intraperitoneal injections of urethane and placed in a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. In vivo electrophysiological recordings were then performed to measure population spike (PS) amplitude and excitatory postsynaptic potential (EPSP) slope in the hippocampal dentate gyrus. Long-term potentiation (LTP) was induced by high-frequency stimulation of the perforant pathway. Blood samples were then collected to measure plasma levels of triglycerides, low-density lipoproteins, very low-density lipoprotein, and cholesterol. After induction of LTP, PS amplitude and EPSP slope were significantly decreased in Aβ-injected rats fed a HFD compared to vehicle-injected animals or untreated animals that were fed a normal diet. Met treatment of Aβ-injected rats significantly attenuated these decreases, suggesting that Met decreased the effects of Aβ on LTP. These findings suggest that Met treatment is neuroprotective against the detrimental effects of Aβ and HFDs on hippocampal synaptic plasticity. © 2016 Elsevier Inc.
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