Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1) on startle behavior and sensorimotor gating.
Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1) on startle behavior and sensorimotor gating.
复制标题
DOI：
10.1016/j.psyneuen.2014.12.005
复制
发表时间：
2015-03
影响因子：
3.7
通讯作者：
Deussing, Jan M.
中科院分区：
文献类型：
--
作者：
Flandreau, Elizabeth;Risbrough, Victoria;Lu, Ailing;Ableitner, Martin;Geyer, Mark A.;Holsboer, Florian;Deussing, Jan M.
促肾上腺皮质激素释放因子（CRF）家族的肽和受体协调哺乳动物的内分泌，自主神经和行为反应的压力。过度的CRF产生与应激敏感性精神障碍如创伤后应激障碍（PTSD）的病因学有关，PTSD与惊吓可塑性的改变有关。CRF家族的肽和受体介导应激期间的急性惊吓反应变化，慢性CRF激活可诱导惊吓异常。为了确定什么样的神经回路调节惊吓以响应慢性CRF激活，在惊吓可塑性的多个领域中比较了在整个中枢神经系统（CNS; CRF-COECNS）中过表达CRF或仅限于抑制性GABA能神经元（CRF-COEGABA）的转基因小鼠。整个CNS中CRF过度表达增加了惊吓程度并降低了抑制惊吓的能力（降低了习惯性和降低了前脉冲抑制（PPI）），与之前报告的CRF外源性作用相似。相反，CRF过度表达局限于抑制性神经元减少惊吓幅度，但对抑制措施没有影响。急性CRF受体1（CRF 1）拮抗剂治疗减弱只有CNS特异性CRF过表达引起的惊吓的影响。前脑主要神经元CRF 1受体的特异性缺失未能改变外源性CRF或应激对惊吓的影响，这表明这些表达CRF 1的神经元不需要CRF诱导的惊吓行为变化。这些数据表明，CRF激活对惊吓行为的影响利用了广泛的神经回路，包括前脑和非前脑区域。此外，这些研究结果表明，增加CRF释放的神经源决定了惊吓表型引起的。可以想象，这可以解释为什么以脑脊液中CRF增加为特征的疾病（例如PTSD和重度抑郁症）在惊吓反应方面具有不同的症状特征。
The corticotropin-releasing factor (CRF) family of peptides and receptors coordinates the mammalian endocrine, autonomic, and behavioral responses to stress. Excessive CRF production has been implicated in the etiology of stress-sensitive psychiatric disorders such as posttraumatic stress disorder (PTSD), which is associated with alterations in startle plasticity. The CRF family of peptides and receptors mediate acute startle response changes during stress, and chronic CRF activation can induce startle abnormalities. To determine what neural circuits modulate startle in response to chronic CRF activation, transgenic mice overexpressing CRF throughout the central nervous system (CNS; CRF-COECNS) or restricted to inhibitory GABAergic neurons (CRF-COEGABA) were compared across multiple domains of startle plasticity. CRF overexpression throughout the CNS increased startle magnitude and reduced ability to inhibit startle (decreased habituation and decreased prepulse inhibition (PPI)), similar to previous reports of exogenous effects of CRF. Conversely, CRF overexpression confined to inhibitory neurons decreased startle magnitude but had no effect on inhibitory measures. Acute CRF receptor 1 (CRF1) antagonist treatment attenuated only the effects on startle induced by CNS-specific CRF overexpression. Specific deletion of CRF1 receptors from forebrain principal neurons failed to alter the effects of exogenous CRF or stress on startle, suggesting that these CRF1 expressing neurons are not required for CRF-induced changes in startle behaviors. These data indicate that the effects of CRF activation on startle behavior utilize an extensive neural circuit that includes both forebrain and non-forebrain regions. Furthermore, these findings suggest that the neural source of increased CRF release determines the startle phenotype elicited. It is conceivable that this may explain why disorders characterized by increased CRF in cerebrospinal fluid (e.g. PTSD and major depressive disorder) have distinct symptom profiles in terms of startle reactivity.
登录
查看更多内容
DOI：
10.1111/j.1749-6632.1997.tb48289.x
发表时间：
1997-01-01
期刊：
PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER
影响因子：
--
作者：
Davis, M;Walker, DL;Lee, YL
通讯作者：
Lee, YL
DOI：
10.1017/s1461145710001409
发表时间：
2011-10
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Gresack JE;Risbrough VB
通讯作者：
Risbrough VB
影响因子：
3.7
作者：
GRAHAM, FK
通讯作者：
GRAHAM, FK
影响因子：
5.2
作者：
Hauger RL;Risbrough V;Oakley RH;Olivares-Reyes JA;Dautzenberg FM
通讯作者：
Dautzenberg FM
影响因子：
16.2
作者：
Monory, Krisztina;Massa, Federico;Lutz, Beat
通讯作者：
Lutz, Beat