Enhanced catecholamine synthesis in the prefrontal cortex after traumatic brain injury: Implications for prefrontal dysfunction
Enhanced catecholamine synthesis in the prefrontal cortex after traumatic brain injury: Implications for prefrontal dysfunction
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DOI：
10.1089/neu.2006.23.1094
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发表时间：
2006-07-01
影响因子：
4.2
通讯作者：
Dash, Pramod K.
中科院分区：
文献类型：
--
作者：
Kobori, Nobuhide;Clifton, Guy L.;Dash, Pramod K.
创伤性脑损伤（TBI）引起的前额叶皮层功能障碍导致许多高水平的认知缺陷，包括工作记忆（WM）功能障碍。WM是许多高级功能的核心，但其功能障碍的细胞和分子机制知之甚少。啮齿类动物的病变和药理学研究表明，WM任务涉及内侧前额叶皮层（mPFC），其中包括前边缘/边缘下（PL/IL）皮层。这些研究表明，最佳水平的儿茶酚胺神经传递是至关重要的WM功能的正常，这表明，在他们的合成的改变可能在WM功能障碍发挥作用。使用创伤性脑损伤的皮质撞击损伤模型，可重复地导致啮齿动物的工作记忆缺陷，我们测量了蛋白质水平和酪氨酸羟化酶（TH）的活性，儿茶酚胺生物合成的限速酶，和组织多巴胺（DA）和去甲肾上腺素（NE）水平在显微解剖PL/IL组织。我们的结果表明，TBI增加TH蛋白水平，其活性和组织DA和NE含量在PL/IL。这些研究结果表明，改变儿茶酚胺信号内的PL/IL可能有助于受损的PFC功能，并可能在设计和实施的策略，以减轻脑损伤患者的前额叶功能障碍的影响。
Traumatic brain injury (TBI)-induced dysfunction of the prefrontal cortex causes many high-level cognitive deficits, including working memory (WM) dysfunction. WM lies at the core of many high-level functions, yet the cellular and molecular mechanisms underlying its dysfunction are poorly understood. Lesion and pharmacological studies in rodents have implicated the medial prefrontal cortex (mPFC), which includes the prelimbic/infralimbic (PL/IL) cortices, in WM tasks. These studies have shown that optimal levels of catecholamine neurotransmission are critical for normalcy of WM function, suggesting that alterations in their synthesis may play a role in WM dysfunction. Using the cortical impact injury model of traumatic brain injury which reproducibly causes working memory deficits in rodents, we have measured the protein levels and activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine biosynthesis, and tissue dopamine (DA) and norepinephrine (NE) levels in microdissected PL/IL tissues. Our results show that TBI increases TH protein levels, its activity and tissue DA and NE content in the PL/IL. These findings suggest that altered catecholamine signaling within the PL/IL may contribute to impaired PFC function, and may have implications in the design and implementation of strategies to alleviate prefrontal dysfunction in brain injury patients.