Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress.
Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress.
复制标题
DOI：
10.3389/fnbeh.2017.00177
复制
发表时间：
2017
影响因子：
3
通讯作者：
Buhusi CV
中科院分区：
文献类型：
--
作者：
Buhusi M;Brown CK;Buhusi CV
对压力的反应增加是适应不良的，与异常行为和精神病理学有关。慢性不可预测的压力（CUS）改变了儿茶酚胺能神经传递和重塑神经元回路参与学习，注意力和决策。胶质源性神经营养因子（GDNF）对黑质多巴胺能神经元和蓝斑去甲肾上腺素能神经元的生理和存活至关重要。在应激过程中GDNF表达的上调与恢复力有关;另一方面，由于遗传或表观遗传修饰，GDNF在应激反应中不能上调，诱导行为改变。例如，暴露于慢性应激的GDNF缺陷小鼠表现出执行功能的改变，例如时间折扣增加。在这里，我们研究了CUS对GDNF杂合（HET）小鼠及其野生型（WT）同窝对照小鼠的潜伏抑制（LI）（一种选择性注意力和学习的测量）的影响。在基线实验条件下，GDNF HET和WT小鼠之间的LI没有差异。然而，在CUS后，GDNF缺陷小鼠未能表达LI。此外，应激的GDNF-HET小鼠，而不是其WT对照，显示出减少的神经元激活（c-Fos阳性神经元的数量）在核壳和增加的激活在核的核心，两个关键区域的LI的表达。我们的研究结果将LI添加到受慢性应激影响的行为列表中，并支持GDNF缺陷在精神分裂症和其他精神疾病相关的应激诱导的病理行为中的作用。
Increased reactivity to stress is maladaptive and linked to abnormal behaviors and psychopathology. Chronic unpredictable stress (CUS) alters catecholaminergic neurotransmission and remodels neuronal circuits involved in learning, attention and decision making. Glial-derived neurotrophic factor (GDNF) is essential for the physiology and survival of dopaminergic neurons in substantia nigra and of noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression during stress is linked to resilience; on the other hand, the inability to up-regulate GDNF in response to stress, as a result of either genetic or epigenetic modifications, induces behavioral alterations. For example, GDNF-deficient mice exposed to chronic stress exhibit alterations of executive function, such as increased temporal discounting. Here we investigated the effects of CUS on latent inhibition (LI), a measure of selective attention and learning, in GDNF-heterozygous (HET) mice and their wild-type (WT) littermate controls. No differences in LI were found between GDNF HET and WT mice under baseline experimental conditions. However, following CUS, GDNF-deficient mice failed to express LI. Moreover, stressed GDNF-HET mice, but not their WT controls, showed decreased neuronal activation (number of c-Fos positive neurons) in the nucleus accumbens shell and increased activation in the nucleus accumbens core, both key regions in the expression of LI. Our results add LI to the list of behaviors affected by chronic stress and support a role for GDNF deficits in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.
登录
查看更多内容
影响因子：
1.9
作者：
GOOD, M;HONEY, RC
通讯作者：
HONEY, RC
影响因子：
10.6
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
2.7
作者：
Buhusi M;Obray D;Guercio B;Bartlett MJ;Buhusi CV
通讯作者：
Buhusi CV
影响因子：
1.9
作者：
Buhusi, CV;Gray, JA;Schmajuk, NA
通讯作者：
Schmajuk, NA
影响因子：
2.7
作者：
Coutureau, E;Galani, R;Di Scala, G
通讯作者：
Di Scala, G