Neuroprotective Role of Antidiabetic Drug Metformin Against Amyloid Β Peptide-Induced Neuronal Loss in Hippocampal Ca1 Pyramidal Neurons in Rats Fed High Fat Diet



Azadeh EH¹ ; Asadbegi M² ; Salehi I¹ ; Yaghmaei P^{3, 4} ; Komaki A² Show Affiliations
Source: Journal of Chemical and Pharmaceutical Sciences Published:2016

Abstract

Three pathological hallmarks of Alzheimer's disease (AD) include extracellular senile plaques, intracellular neurofibrillary tangles and neuron loss in the hippocampus and the associated neocortex. Metformin (Met) is able to exert an effective neuroprotective effect and also is used to treat neurodegenerative disorders such as AD. On the contrary, overweight and high fat diets (HFDs) are known to increase the risk of AD. Here, we investigated the neuroprotective effects of Met on β-Amyloid (Aβ)-induced deficiencies in density of hippocampal CA1pyramidal neurons in AD model rats that were fed a HFD. In the current study, 32 adult male Wistar rats were randomly assigned to four groups (n=8): group 1 (control); group 2 (HFD+vehicle); group 3 (HFD+Aβ); or group 4 (Met+HFD+Aβ). Rats pretreated with Met along with feeding an HFD for 8 weeks, and then Aβ injected intrahippocampally in order to induce AD. The numbers of the living hippocampal CA1 pyramidal cells were numbered as neuronal mass. The results showed that numbers of pyramidal neurons in rat hippocampal CA1 subfield were significantly decreased in Aβ-injected rats fed an HFD compared to control and vehicle-injected animals. Met pretreatment along with HFD consumption in Aβ-injected rats significantly attenuated these decreases, suggesting that Met decreased the effects of Aβ on neuron loss and presented neuroprotective effect. These findings suggest that Met pretreatment is neuroprotective against the detrimental effects of Aβ and HFDs on hippocampal neuron survival.