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

• Published in: Neuromolecular medicine 2015-06, Vol.17 (2), p.121-136
• Main Authors: Amin, Shaimaa Nasr, El-Aidi, Ahmed Amro, Ali, Mohamed Mostafa, Attia, Yasser Mahmoud, Rashed, Laila Ahmed
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Anxiety - blood; Anxiety - drug therapy; Anxiety - etiology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - biosynthesis; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Amino Acid Antagonists - therapeutic use; Freezing Reaction, Cataleptic - drug effects; Freezing Reaction, Cataleptic - physiology; Gene Expression Regulation - drug effects; Grooming - drug effects; Grooming - physiology; Hippocampus - chemistry; Hippocampus - drug effects; Hippocampus - physiopathology; Hydrocortisone - blood; Interleukin-6 - blood; Internal Medicine; Male; Maze Learning - drug effects; Maze Learning - physiology; Memantine - pharmacology; Memantine - therapeutic use; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurogenesis - drug effects; Neurology; Neuronal Plasticity - drug effects; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Original Paper; Rats; Rats, Wistar; Restraint, Physical - adverse effects; Spatial Memory - drug effects; Spatial Memory - physiology; Stress, Physiological - drug effects; Stress, Physiological - physiology; Stress, Psychological - blood; Stress, Psychological - drug therapy; Stress, Psychological - etiology; Stress, Psychological - physiopathology; Synaptophysin - biosynthesis; Synaptophysin - genetics; Tumor Necrosis Factor-alpha - blood
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-015-8343-0

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.