Effect of Allopregnanolone on Spatial Memory and Synaptic Proteins in Animal Model of Metabolic Syndrome.

Shaimaa Nasr Amin,Dalia Azmy Elberry,Shaimaa Abdalaleem Abdalgeleel,Mubarak Ali Algahtany,Walaa Bayoumie El Gazzar,Sherif Ahmed Shaltout

doi:10.3390/brainsci11050644

Shaimaa Nasr Amin, Dalia Azmy Elberry + Show 4 more

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https://doi.org/10.3390/brainsci11050644

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Abstract

Metabolic Syndrome (MetS) is considered a common disorder, especially with a sedentary lifestyle and unhealthy food consumption. Cognitive impairment is one of the MetS consequences that worsens the quality of life of the patients. The study aimed to assess the therapeutic effect of the neurosteroid Allopregnalonone on spatial memory and, therefore, the expression of two synaptic plasticity markers in the hippocampus. Thirty-two male rats were divided into four groups: control groups, MetS, and MetS + Allopregnalone. Spatial memory has been evaluated by the Y-maze task and blood pressure measured by the rat tail method. Biochemical evaluation of serum glucose, insulin, lipid profile, and hippocampal expression of Synaptophysin and Associated Protein 43 (GAP-43) were performed for assessing Allopregnanolone on serum and hippocampal markers. Allopregnanolone therapy improved working spatial memory, hypertension, and biochemical markers measured in the serum and hippocampus.

Highlights

Metabolic syndrome (MetS) is a common metabolic disorder correlated to a sedentary lifestyle and junk food consumption
Mean HOMA-insulin resistance (IR): it was significantly higher in MetS than in other groups ((p-value < 0.001), and it was significantly higher in MetS + Allopregnanolone than negative control for Allopregnanolone and positive control for Allopregnanolone (p-value < 0.001)
Mean serum Triglycerides: it was significantly higher in MetS than negative control for Allopregnanolone and positive control for Allopregnanolone (p-value < 0.001), and it was significantly higher in MetS + Allopregnanolone than negative control for Allopregnanolone and positive control for Allopregnanolone (p-value < 0.001; 0.001 respectively)

Summary

Introduction

Metabolic syndrome (MetS) is a common metabolic disorder correlated to a sedentary lifestyle and junk food consumption. The syndrome manifestations are abnormal lipid profile, hypertension, hyperglycemia, insulin resistance (IR), and abdominal obesity [1]. Cognitive dysfunction and dementia are known comorbidities associated with MetS. The suggested mechanisms for impaired cognition in MetS may be related to oxidative stress, abnormal metabolism, inflammation, and vascular reactivity abnormalities. These abnormalities, in turn, disturb the homeostasis of the internal environment around the neurons under basal conditions and more impairment during activity [2]. As encountered in the metabolic syndrome, insulin resistance is found to reduce neurosteroids [3], and neurosteroids administration has been found to improve hypertension in obesity [4]

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