Chemokine CCL2 impairs spatial memory and cognition in rats via influencing inflammation, glutamate metabolism and apoptosis-associated genes expression- a potential mechanism for HIV-associated neurocognitive disorder.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
    • Publication Information:
      Publication: <2008->: Amsterdam : Elsevier
      Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
    • Subject Terms:
      Chemokine CCL2/*metabolism ; HIV Infections/*complications ; Inflammation/*pathology ; Memory Disorders/*physiopathology ; Neurocognitive Disorders/*physiopathology; Animals ; Apoptosis/physiology ; Chemokine CCL2/administration & dosage ; Cognition/physiology ; Disease Models, Animal ; Glutamic Acid/metabolism ; Hippocampus/pathology ; Male ; Maze Learning/physiology ; Neurocognitive Disorders/virology ; Neurons/pathology ; Rats ; Rats, Sprague-Dawley ; Spatial Memory/physiology
    • Abstract:
      Aims: To explore the role of chemokine CC motif ligand 2 (CCL2) in spatial memory and cognition impairment, and the underlying mechanisms focused on inflammatory, glutamate metabolistic and apoptotic- associated mRNA expression.
      Materials and Methods: Stereotaxic surgery was performed here to establish a rat model by bilateral intra-hippocampal injection of CCL2. Morris water maze (MWM) and Novel object recognition test (NORT) were used to assess the learning, memory and cognitive ability respectively. RT-PCR was used to detect the relative mRNA expression of inflammatory, glutamate metabolistic and apoptotic- associated indexes. Nissl and TUNEL staining were performed to observe the morphological changes of hippocampal CA1 zone and quantified the apoptosis of hippocampal neurons of CA1 zones respectively.
      Key Findings: We found CCL2 injured cognitive function in rats. Six days after CCL2 injection, we revealed the following obvious mRNA expression changes: (1) increasing of the neuroinflammatory cytokines IL-1β, CXCL-10, IL-6; (2) decreasing of the glutamate transporters GLT-1 and GLAST and increasing of PAG; (3) increasing of the apoptotic genes caspase-8, caspase-3 and Bax, while decreasing the anti-apoptotic gene Bcl-2. Further, Nissl staining and TUNEL confirmed the injury of the structure of hippocampal CA1 zones and the apoptosis of hippocampal neurons.
      Significance: Our results indicated that CCL2 impaired spatial memory and cognition, the involving mechanisms may link to the up-regulation of mRNA expression of the three major pathological events: inflammation, excitotoxicity and neuronal apoptosis, which were involved in HIV-associated neurocognitive disorder (HAND). Taken together, these findings suggest a potential therapeutic strategy against CCL2.
      Competing Interests: Declaration of competing interest I would like to declare that no conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication.
      (Copyright © 2020. Published by Elsevier Inc.)
    • Contributed Indexing:
      Keywords: Apoptosis; CCL2; Cognition; Glutamate metabolism; Inflammation; Spatial memory
    • Accession Number:
      0 (Ccl2 protein, rat)
      0 (Chemokine CCL2)
      3KX376GY7L (Glutamic Acid)
    • Publication Date:
      Date Created: 20200527 Date Completed: 20200629 Latest Revision: 20200629
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.lfs.2020.117828
    • Accession Number:
      32454160