Abstract
Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia and is characterized by two neuropathological hallmarks, neuritic plaques and neurofibrillary tangles
Its gene is located within the 6p2424-p25 interval on chromosome 6 [12]. 3 cyclic AMP responsive elements were identified in the promoter region of the gene, suggesting that neuritin expression is mediated by cyclic AMP responsive element binding protein (CREB)
Neuritin is down-regulated in the brains of AD patients First, we examined the levels of neuritin mRNA in the medial frontal gyrus and hippocampus of AD brains and age-matched control subjects by performing Quantitative real-time RT-PCR (qRT-PCR)
Summary
Alzheimer’s disease (AD) is the most common form of dementia and is characterized by two neuropathological hallmarks, neuritic plaques and neurofibrillary tangles. Known as candidate plasticity gene 15 (CPG 15), encodes a small, extracellular glycosylphosphatidylinositol (GPI)anchored cell surface protein [5,6] that was first identified in a screen for activity-regulated genes induced by kainate stimulated seizure in the rat dentate gyrus [7]. 3 cyclic AMP responsive elements were identified in the promoter region of the gene, suggesting that neuritin expression is mediated by cyclic AMP responsive element binding protein (CREB). An in vivo study showed an important role for CREB in activity-dependent neuritin expression in the barrel cortex of control and CREB a, D-knockout mice. In CREB mutant mice, neuritin expression is not induced to the same extent as in wild-type (wt) littermates, indicating that CREB is necessary for neuritin regulation during receptive field plasticity in the adult cortex [13]
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