Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.
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 ident...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2015
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| _version_ | 1797103478658564096 |
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| author | Pristerà, A Lin, W Kaufmann, A Brimblecombe, K Threlfell, S Dodson, P Magill, P Fernandes, C Cragg, S Ang, S |
| author_facet | Pristerà, A Lin, W Kaufmann, A Brimblecombe, K Threlfell, S Dodson, P Magill, P Fernandes, C Cragg, S Ang, S |
| author_sort | Pristerà, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:20:42Z |
| format | Journal article |
| id | oxford-uuid:f29ef729-2094-4610-8062-734e74a7b615 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:20:42Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:f29ef729-2094-4610-8062-734e74a7b6152022-03-27T12:05:17ZTranscription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f29ef729-2094-4610-8062-734e74a7b615EnglishSymplectic Elements at OxfordNational Academy of Sciences2015Pristerà, ALin, WKaufmann, ABrimblecombe, KThrelfell, SDodson, PMagill, PFernandes, CCragg, SAng, SMidbrain 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. |
| spellingShingle | Pristerà, A Lin, W Kaufmann, A Brimblecombe, K Threlfell, S Dodson, P Magill, P Fernandes, C Cragg, S Ang, S Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title | Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title_full | Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title_fullStr | Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title_full_unstemmed | Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title_short | Transcription factors FOXA1 and FOXA2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice. |
| title_sort | transcription factors foxa1 and foxa2 maintain dopaminergic neuronal properties and control feeding behavior in adult mice |
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