Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders.
J Neurovirol
; 18(4): 313-22, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22234543
ABSTRACT
FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (p < 0.0001, U test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (p = 0.02, U test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (p = 0.08, Kruskal-Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Complejo SIDA Demencia
/
Giro Parahipocampal
/
Proteínas de Unión a Tacrolimus
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurovirol
Asunto de la revista:
NEUROLOGIA
/
VIROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos