title: Immunological alteration & toxic molecular inductions leading to cognitive impairment & neurotoxicity in transgenic mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  Inflammation is considered to be one of the crucial pathological factors associated with the development of Alzheimer's disease, although supportive experimental evidence remains undiscovered. Therefore, the current study was carried out to better understand and establish the pathophysiological involvement of chronic inflammation in a double transgenic mouse model of Alzheimer's disease.
  
  
  METHODS
  We analyzed amyloid-beta deposition, oxidative stress, biochemical, neurochemical and immunological markers in a 10month old (APΔE9) mouse model. Memory functions were assessed by behavioral testing followed by measurement of synaptic plasticity via extracellular field recordings.
  
  
  RESULTS
  Substantial increases in amyloid-beta levels, beta-secretase activity, and oxidative stress, along with significant neurochemical alterations in glutamate and GABA levels were detected in the brain of APΔE9 mice. Interestingly, marked elevations of pro-inflammatory cytokines in whole brain lysate of APΔE9 mice were observed. Flow cytometric analysis revealed a higher frequency of CD4+ IL-17a and IFN-γ secreting T-cells in APΔE9 brain, indicating a robust T-cell infiltration and activation. Behavioral deficits in learning and memory tasks, along with impairment in long-term potentiation and associated biochemical changes in the expression of glutamatergic receptor subunits were evident.
  
  
  CONCLUSIONS
  Thus, this study establishes the role by which oxidative stress, alterations in glutamate and GABA levels and inflammation increases hippocampal and cortical neurotoxicity resulting in the cognitive deficits associated with Alzheimer's disease.
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Manuj
authors.initials: M
authors.lastname: Ahuja
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Manal
authors.initials: M
authors.lastname: Buabeid
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA; Center for Aging and Associated Diseases, Helmy Institute of Medical Sciences, Zewail City of Science and Technology, Giza, Egypt.
authors.forename: Engy
authors.initials: E
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Majrashi
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Kodeeswaran
authors.initials: K
authors.lastname: Parameshwaran
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Amin
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Sindhu
authors.initials: S
authors.lastname: Ramesh
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Kariharan
authors.initials: K
authors.lastname: Thiruchelvan
authors.affiliation: Department of Anatomy and Physiology, College of Veterinary Science, Auburn University, AL 36849, USA.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Pondugula
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy (HSOP), Auburn University, AL 36849, USA. Electronic address: dhanamu@auburn.edu.
authors.forename: Muralikrishnan
authors.initials: M
authors.lastname: Dhanasekaran
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D018384:Oxidative Stress / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer's disease; Amyloid-beta; Excitotoxicity; Inflammation; Oxidative stress; T-cell