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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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- Author(s): Chen J;Chen J; Tan L; Tan L; Liao Y; Liao Y; Long J; Long J; Zhou Y; Zhou Y; Wei J; Wei J; Zhou Y; Zhou Y
- Source:
Life sciences [Life Sci] 2020 Aug 15; Vol. 255, pp. 117828. Date of Electronic Publication: 2020 May 23.- Publication Type:
Journal Article- Language:
English - Source:
- 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
- Source:
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