4.7 Article

Cerebral Dopamine Neurotrophic Factor Regulates Multiple Neuronal Subtypes and Behavior

期刊

JOURNAL OF NEUROSCIENCE
卷 40, 期 32, 页码 6146-6164

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2636-19.2020

关键词

dopamine; GABA; growth factors; histamine; neurotransmitters; Parkinson's disease

资金

  1. Jane and Aatos Erkko Foundation
  2. Sigrid Juselius Foundation
  3. Magnus Ehrnrooth's Foundation
  4. Finska Lakaresallskapet
  5. Biocenter Finland

向作者/读者索取更多资源

Cerebral dopamine neurotrophic factor (CDNF) protects dopaminergic neurons against toxic damage in the rodent brain and is in clinical trials to treat Parkinson's disease patients. Yet the underlying mechanism is poorly understood. To examine its significance for neural circuits and behavior, we examined the development of neurotransmitter systems from larval to male adult mutant zebrafish lacking cdnf. Although a lack of cdnf did not affect overall brain dopamine levels, dopaminergic neuronal clusters showed significant abnormalities. The number of histamine neurons that surround the dopaminergic neurons was significantly reduced. Expression of tyrosine hydroxylase 2 in the brain was elevated in cdnf mutants throughout their lifespan. There were abnormally few GABA neurons in the hypothalamus in the mutant larvae, and expression of glutamate decarboxylase was reduced throughout the brain. cdnf mutant adults showed a range of behavioral phenotypes, including increased sensitivity to pentylenetetrazole-induced seizures. Shoaling behavior of mutant adults was abnormal, and they did not display social attraction to conspecifics. CDNF plays a profound role in shaping the neurotransmitter circuit structure, seizure susceptibility, and complex behaviors in zebrafish. These findings are informative for dissecting the diverse functions of this poorly understood factor in human conditions related to Parkinson's disease and complex behaviors.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据