Abstract
Paired immunoglobulin-like receptor B (PirB), a functional receptor for myelin-associated inhibitory proteins, plays an important role in axon regeneration in injured brains. However, its role in normal brain function with age has not been previously investigated. Therefore in this study, we examined the expression level of PirB in the cerebral cortex, hippocampus and cerebellum of mice at 1 month, 3 months and 18 months of age. The results showed that the expression of PirB increased with age. We further demonstrated that overexpression of PirB inhibited neurite outgrowth in PC12 cells, and this inhibitory activity of PirB could be reversed by TAT-PEP, which is a recombinant soluble PirB ectodomain fused with TAT domain for blood-brain barrier penetration. In vivo study, intraperitoneal administration of TAT-PEP was capable of enhancing motor capacity and spatial learning and memory in mice, which appeared to be mediated through regulation of brain-derived neurotrophic factor (BDNF) secretion. Our study suggests that PirB is associated with aging and TAT-PEP may be a promising therapeutic agent for modulation of age-related motor and cognitive dysfunctions.
Highlights
Paired immunoglobulin-like receptor B (PirB) is a functional receptor for myelin-associated inhibitory proteins, including Nogo, myelin-associated glycoprotein (MAG) and oligodendrocytemyelin glycoprotein (OMgp), which inhibit axonal regeneration and functional recovery after brain injury (Gou et al, 2014)
We studied the impact of PirB on axon outgrowth using PirB-overexpressed PC12 cells, PC12PirB, which were generated through lentiviral transduction
We explored the potential mechanism for TAT-PEP-mediated motor and cognitive behavior enhancement by analyzing the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of 18 months mice
Summary
Paired immunoglobulin-like receptor B (PirB) is a functional receptor for myelin-associated inhibitory proteins, including Nogo, myelin-associated glycoprotein (MAG) and oligodendrocytemyelin glycoprotein (OMgp), which inhibit axonal regeneration and functional recovery after brain injury (Gou et al, 2014). The expression level of PirB in neurons has been shown to increase after neurological injuries, including spinal cord injuries (Zhou et al, 2010), hypoxic-ischemic brain damage (Adelson et al, 2012; Wang et al, 2012; Guo et al, 2013), encephalitis (Deng et al, 2012), hippocampal aging (VanGuilder Starkey et al, 2012) and retinopathy (Cai et al, 2012). The expression of PirB was found to gradually increase in the CA1 and DG subregions of the hippocampus in aging mice with cognitive behavior
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