NutraStem as a neuroprotectant: Implications for neurogenesis in HAART treated patients

NutraStem 作为神经保护剂：对 HAART 治疗患者神经发生的影响

基本信息

批准号：
8923974
负责人：
Brian Giunta
金额：
$ 21.14万
依托单位：
NATURA THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8923974
关键词：
Accounting Address Adherence Adult Adverse effects Affect Age-Months Aging Atrophic Attenuated Autopsy Behavioral Blood Circulation Brain Cell Proliferation Cells Chronic Cognition Cognition Disorders Cognitive Cognitive deficits Detection Development Excision Foundations Functional Magnetic Resonance Imaging Future HIV HIV Infections HIV Seropositivity HIV tat Protein HIV-1 Highly Active Antiretroviral Therapy Hippocampus (Brain)Immunohistochemistry Impaired cognition Impairment In Vitro Individual Infection Control Lamivudine Lead Learning Mediating Mediator of activation protein Memory Messenger RNA Mind Mitochondria Mus Neurocognition Neurocognitive Neurocognitive Deficit Neurodegenerative Disorders Neurons Neuroprotective Agents Oxidative Stress Parahippocampal Gyrus Pathology Patients Peripheral Population Prevalence Prevention Process Production Reactive Oxygen Species Regimen Risk Factors Short-Term Memory Stress Task Performances Testing Transgenic Mice Transgenic Organisms Viral Viral Load result Virus Zidovudine base cell type dentate gyrus design efavirenz experience in vivo mouse model nerve stem cell neurocognitive test neurogenesis neuroprotection neurotoxic neurotoxicity non-nucleoside reverse transcriptase inhibitors novel object recognition prevent public health relevance relating to nervous system research study respiratory stem cell population tat Protein trend virtual

项目摘要

DESCRIPTION (provided by applicant): We designed an experiment to understand the interactions between loss of development of new neurons (neurogenesis) in the brain, HIV-1 Tat protein, and the known cognitive side-effects imparted by chronic highly active antiretroviral therapy (HAART). We preliminarily found the common HAART combination for HIV patients ,lamivudine/zidovudine/efavirenz (3TC/AZT/EFV): (1) reduced primary neural stem cell proliferation in vitro (2) increased NSC mitochondrial oxidative stress and that these could be opposed in vitro by NutraStem(r). We also show this regimen decreases hippocampal neurogenesis in vivo. We hypothesize NutraStem(r) will oppose HAART and Tat mediated neurogenesis pathology by reducing the effect of these two components on mitochondrial stress, in turn promoting neurogenesis, and reducing neurocognitive deficits in HIV-1 Tat transgenic mice. Here we plan to characterize neurocognition, and neurogenesis in HIV-1 Tat mice chronically treated with HAART. EFV or EFV/3TC/AZT should lead to advanced neurocognitive deficits in these mice that should be enhanced by brain HIV-1 Tat expression which that can be correlated with decreases in neurogenesis, compared to control AZT, or 3TC treated mice. NutraStem(r) should attenuate this phenomenon. We expect that other indicators of this NutraStem(r) mediated neuroprotection will include a reduction of memory problems which will be tested and brain mitochondrial stress in the Tat/HAART exposed mice. This study is expected to describe the long-term consequences of chronic Tat expression with use of a common HAART regimen plus a neuroprotectant (NutraStem(r)) in terms of neurogenesis and cognitive deficits. It should lay the foundation for effective strategies to prevent these interactions between Tat, HAART, and neurogenesis in the future in the context of a known HAART-mediated pathophysiological mechanism.

描述（通过应用程序提供）：我们设计了一个实验，以了解大脑中新神经元（神经发生）丧失的相互作用，HIV-1 TAT蛋白与已知的认知副作用，由慢性高度活性抗逆转录病毒疗法（HAART）赋予的已知认知副作用。我们初步发现了HIV患者的常见HAART组合，Lamivudine/Zidovudine/Efavirenz（3TC/AZT/EFV）：（1）（1）减少体外原发性神经干细胞增殖（2）增加NSC线粒体氧化应激，并且这些可能与nutrastem相反。我们还显示该方案降低了体内海马神经发生。我们假设Nutrastem（R）将通过减少这两个成分对线粒体应激的影响，促进神经发生并减少HIV-1 TAT转基因小鼠的神经认知缺陷，反对HAART和TAT介导的神经发生病理学。在这里，我们计划表征神经认知和用HAART长期治疗的HIV-1 TAT小鼠中的神经发生。 EFV或EFV/3TC/AZT应导致这些小鼠的高级神经认知定义，与对照AZT或3TC治疗的小鼠相比，该脑HIV-1 TAT表达应与神经发生下的下降相关。 Nutrastem（R）应减轻这种现象。我们预计该Nutrastem（R）介导的神经保护作用的其他指标将包括记忆问题的减少，这些记忆问题将被测试，并且在TAT/HAART暴露的小鼠中脑部线粒体应激。预计这项研究将通过神经发生和认知缺陷来描述使用常见的HAART方案以及神经保护剂（Nutrastem（R））的长期后果。应在已知的HAART介导的病理生理机制的背景下为未来的TAT，HAART和神经发生之间的相互作用奠定基础。