Neurotrophins modulate the expression of chemokine receptors in the brain

Abstract

In the central nervous system, chemokines are primarily mediators of inflammatory processes. Their receptors, in particular, CXCR4 and CCR5, serve as co-factors along with CD4 that permit Human immunodeficiency virus-1 (HIV) infection. Moreover, experimental evidence has shown that CXCR4 and CCR5 mediate the neurotoxic effects of the HIV envelope protein gp120, suggesting that these receptors could also promote the neuropathogenesis observed in HIVpositive individuals. Therefore, a better understanding of the molecular mechanisms governing the expression of chemokine receptors in the brain may lead to improved therapies that reduce HIV neurotoxicity. This study presents evidence that the expression of chemokine receptors in the brain is modulated by two neurotrophins in an area-specific manner. This new evidence suggests that the neurotrophins may be an adjunct therapy to reduce HIV-mediated neuronal injury evoked by chemokine receptor activation.

Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury

“…In the adult brain, non-neuronal cells such as microglia, astrocytes and oligodendrocytes express this receptor (He et al, 1997; Klein et al, 1999; van der Meer et al, 2000). Nevertheless, CCR5 is also expressed by neurons, although this expression varies between species, methods of detection, and type of cultures (Avdoshina et al, 2011; Klein et al, 1999; Rottman et al, 1997; van der Meer et al, 2000). CCR5 is also the main receptor that mediates the neurotoxic effect of M-tropic gp120.…”

Success with neurotropin in treating pediatric lower extremity pain induced by spinal cord injury after epidural anesthesia

“…Recent clinical and basic studies verified the effectiveness of neurotropin on analgesia and neuroprotection while treating neuropathic pain as well as primary headache 7–12. Meanwhile, one Japanese report established the safety of neurotropin when used in childhood.…”

When Human Immunodeficiency Virus Meets Chemokines and Microglia: Neuroprotection or Neurodegeneration?

“…These include the molecular layer, the granular and polymorphic layers, and the stratum lacunosum molecularis (Stumm et al, 2002). CCR5 is expressed by microglia cells and promotes their proliferation; however, it has also been localized in various neuronal populations in vivo , including cortical and striatal neurons, cerebellar Purkinje cells, and hippocampal pyramidal neurons (Westmoreland et al, 2002; Avdoshina et al, 2011). …”