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.
Life Sci
; 255: 117828, 2020 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-32454160
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 ANDMETHODS:
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. KEYFINDINGS:
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-1ß, 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Quimiocina CCL2
/
Transtornos Neurocognitivos
/
Inflamação
/
Transtornos da Memória
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2020
Tipo de documento:
Article