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Modification of Hippocampal Markers of Synaptic Plasticity by Memantine in Animal Models of Acute and Repeated Restraint Stress: Implications for Memory and Behavior

NeuroMolecular Medicine volume 17, pages 121–136 (2015)Cite this article

Abstract

Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer’s disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

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Authors and Affiliations

  1. Department of Medical Physiology, Kasr Al Ainy Faculty of Medicine, Cairo University, Al Manyal, Cairo, 11451, Egypt

    Shaimaa Nasr Amin

  2. Faculty of Pharmacy, MSA University, Cairo, Egypt

    Ahmed Amro El-Aidi, Mohamed Mostafa Ali & Yasser Mahmoud Attia

  3. Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt

    Laila Ahmed Rashed

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  1. Shaimaa Nasr Amin
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  2. Ahmed Amro El-Aidi
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  3. Mohamed Mostafa Ali
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  4. Yasser Mahmoud Attia
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  5. Laila Ahmed Rashed
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Correspondence to Shaimaa Nasr Amin.

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Amin, S.N., El-Aidi, A.A., Ali, M.M. et al. Modification of Hippocampal Markers of Synaptic Plasticity by Memantine in Animal Models of Acute and Repeated Restraint Stress: Implications for Memory and Behavior. Neuromol Med 17, 121–136 (2015). https://doi.org/10.1007/s12017-015-8343-0

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  • DOI: https://doi.org/10.1007/s12017-015-8343-0

Keywords

  • Restraint
  • Memantine
  • Memory
  • Behavior
  • Synaptic plasticity