Corticotropin releasing factor in the nucleus basalis of Meynert impairs attentional performance and reduces levels of glutamate and taurine in male and female rats
Corticotropin releasing factor in the nucleus basalis of Meynert impairs attentional performance and reduces levels of glutamate and taurine in male and female rats
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DOI：
10.1016/j.neuropharm.2022.109280
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发表时间：
2022-10-12
影响因子：
4.7
通讯作者：
Bangasser, Debra A.
中科院分区：
文献类型：
--
作者：
Eck, Samantha R.;Kokras, Nikolaos;Bangasser, Debra A.
以持续注意力受损为特征的精神疾病，包括注意力缺陷多动障碍（ADHD）、创伤后应激障碍（PTSD）和重度抑郁症，也对压力造成的恶化敏感。持续的注意力依赖于从基底前脑的迈纳特基底核（NBM）到内侧前额皮质（mPFC）的胆碱能和非胆碱能投射。我们之前已经表明，应激神经肽促肾上腺皮质激素释放因子（CRF）的中枢给药会损害成年雄性和雌性大鼠持续注意力任务（SAT）的表现。本研究调查了这种效应是否是由 CRF 在 NBM 中的作用介导的。大鼠在 NBM 中接受 CRF，并测量随后的 SAT 表现。高剂量的 CRF (100 ng) 会显着损害不同性别的非信号事件的表现。由于非信号事件的表现被认为取决于非胆碱能（即 GABA 和谷氨酸）信号，因此使用高效液相色谱来量化 NBM 和 mPFC 中的氨基酸水平。我们发现女性 NBM 中谷氨酸、谷氨酰胺、GABA 甘氨酸和丙氨酸的含量高于男性。重要的是，NBM 中的 CRF 导致雄性和雌性中牛磺酸和参与谷氨酸合成的几种氨基酸局部减少，这种变化可能介导 CRF 引起的 SAT 表现缺陷。这些研究共同表明，CRF 对 NMB 中氨基酸的调节会导致压力引起的注意力缺陷。
Psychiatric disorders that are characterized by impairments in sustained attention, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major depression are also sensitive to exacerbation by stress. Sustained attention relies on cholinergic and non-cholinergic projections from the nucleus basalis of Meynert (NBM) in the basal forebrain to the medial prefrontal cortex (mPFC). We have previously shown that central administration of the stress neuropeptide corticotropin releasing factor (CRF) impairs performance on the sustained attention task (SAT) in adult male and female rats. The present study investigated whether this effect was mediated by CRF's action in the NBM. Rats were administered CRF in the NBM and subsequent SAT performance was measured. A high dose of CRF (100 ng) significantly impaired performance on non-signaled events across sex. Because performance on non-signaled events is believed to depend on noncholinergic (i.e., GABA and glutamate) signaling, high performance liquid chromatography was used to quantify amino acid levels in the NBM and mPFC. We found females have higher levels of glutamate, glutamine, GABA glycine, and alanine in the NBM than males. Importantly, CRF in the NBM led to a local decrease of taurine and several amino acids involved in glutamate synthesis in males and females, changes which may mediate the CRFinduced SAT performance deficit. Together these studies suggest that CRF regulation of amino acids in the NMB contributes to stress-induced attention deficits.