Functional consequences of kainate receptor stimulation during neonatal development

新生儿发育过程中红藻氨酸受体刺激的功能后果

• 批准号: 298220-2009
• 负责人: Doucette, Tracy
• 金额: $ 1.46万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=427458
• 关键词: Functional; consequences; kainate; receptor; stimulation

Perinatal (i.e. around the time of birth) brain development is a complex and highly dynamic period in all mammals, including rats and humans. The brain growth spurt in particular, which occurs in late 3rd trimester in humans but in the first 3 postnatal weeks in rats, is a time of massive changes in brain chemistry and in the connections formed between neurons, that will ultimately determine brain function. The complexity of the brain growth spurt also makes it a window of vulnerability for the developing organism, in which seemingly minor trauma or chemical toxicity can result in developmental abnormalities that later manifest in neurological disease. Many of society's most important neurological disorders are often neurodevelopmental in origin, including epilepsy, cerebral palsy, autism, and schizophrenia. Schizophrenia is a psychiatric diagnosis that describes a mental illness generally characterized by impairments in the perception or expression of reality, often in the context of significant social dysfunction. Many believe that damages to the developing nervous system may lay dormant until maturity and then be expressed in the symptoms of schizophrenia. Understanding disease and developing new therapies requires animal models that mimic the origins and the ultimate presentation of the clinical condition. Thus, development and characterization of new models in which hypotheses can be tested can provide insight into mechanisms of human neuropathological diseases. We have previously shown that early alterations in excitatory transmission, during critical periods of brain development, produce lasting changes which are suggestive of some of the symptoms manifested in schizophrenia. The focus of the proposed experiments is to better characterize these changes with respect to their relevance to schizophrenia. Results from these studies will offer a better understanding of the relationship between changes in perinatal glutamatergic signaling and lasting alterations in neurobehaviour and brain circuitry relevant to schizophrenia and other neurological diseases.

围产期（即出生前后）大脑发育是包括大鼠和人类在内的所有哺乳动物的一个复杂和高度动态的时期。尤其是大脑发育突增期，它发生在人类妊娠晚期，但在大鼠出生后的前三周，是大脑化学物质和神经元之间形成的连接发生巨大变化的时期，这将最终决定大脑功能。大脑发育突增的复杂性也使其成为发育生物体的脆弱窗口，在这种情况下，看似轻微的创伤或化学毒性可能导致发育异常，后来表现为神经系统疾病。许多社会上最重要的神经系统疾病往往起源于神经发育，包括癫痫、脑瘫、自闭症和精神分裂症。精神分裂症是一种精神病学诊断，描述了一种精神疾病，通常以感知或表达现实的障碍为特征，通常在严重的社会功能障碍的背景下。许多人认为，对发育中的神经系统的损害可能处于休眠状态，直到成熟，然后表现为精神分裂症的症状。了解疾病和开发新的治疗方法需要动物模型来模拟临床状况的起源和最终表现。因此，可以测试假设的新模型的发展和特征可以提供对人类神经病理疾病机制的见解。我们之前已经表明，在大脑发育的关键时期，兴奋性传递的早期改变会产生持久的变化，这暗示了精神分裂症的一些症状。拟议实验的重点是更好地描述这些变化与精神分裂症的相关性。这些研究的结果将更好地理解围产期谷氨酸能信号的变化与精神分裂症和其他神经系统疾病相关的神经行为和脑回路的持久改变之间的关系。