title: Neuroprotective effects of metformin against Aβ-mediated inhibition of long-term potentiation in rats fed a high-fat diet.
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.
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors: Masoumeh
authors: M
authors: Asadbegi
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Electronic address: Yaghmaei.pa@gmail.com.
authors: Parichehreh
authors: P
authors: Yaghmaei
authors: Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
authors: Iraj
authors: I
authors: Salehi
authors: Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors: Azadeh
authors: A
authors: Ebrahim-Habibi
authors: Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: alirezakomaki@gmail.com.
authors: Alireza
authors: A
authors: Komaki
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001703:Biophysics; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D008055:Lipids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008687:Metformin
keywords: Alzheimer's disease; High-fat diet; Hippocampus; Long term potentiation; Metformin; β-Amyloid