Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice

Pristera Alessandro; Lin Wei; Kaufmann Anna-KristinBrimblecombe Katherine R.Threlfell SarahDodson Paul D.Magill Peter J.Fernandes CathyCragg Stephanie J.Ang Siew-Lan

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Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice

机译：Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice

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Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion of Foxa1/2 results in down-regulation of tyrosine hydroxylase, the rate-limiting enzyme of dopamine (DA) biosynthesis, specifically in dopaminergic neurons of the substantia nigra pars compacta (SNc). In addition, DA synthesis and striatal DA transmission were reduced after Foxa1/2 deletion. Furthermore, the burst-firing activity characteristic of SNc mDA neurons was drastically reduced in the absence of FOXA1/2. These molecular and functional alterations lead to a severe feeding deficit in adult Foxa1/2 mutant mice, independently of motor control, which could be rescued by L-DOPA treatment. FOXA1/2 therefore control the maintenance of molecular and physiological properties of SNc mDA neurons and impact on feeding behavior in adult mice.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第35期|E4929-E4938|共10页
作者
Pristera Alessandro; Lin Wei; Kaufmann Anna-KristinBrimblecombe Katherine R.Threlfell SarahDodson Paul D.Magill Peter J.Fernandes CathyCragg Stephanie J.Ang Siew-Lan;
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作者单位

Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England;

Univ Oxford, Dept Pharmacol, MRC, Brain Network Dynam Unit, Oxford OX1 3TH, England;

Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, EnglandKings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
FOXA1; FOXA2; dopamine; burst firing; feeding;

Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice

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