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Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels
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| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | The Journal of Neuroscience, 26, 2006, 2, S. 530-534 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
|
| Schlagwörter: |
| author_facet |
Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko |
|---|---|
| author |
Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko |
| spellingShingle |
Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko The Journal of Neuroscience Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels General Neuroscience |
| author_sort |
nakamura, kazuhiro |
| spelling |
Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1835-05.2006 <jats:p>Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement in psychiatric conditions and behavioral traits. However,<jats:italic>TPH1</jats:italic>mRNA was reported to be mainly expressed in the pineal gland and the periphery and to be barely detected in the brain. Therefore, contribution of TPH1 to brain 5-HT levels is not known, and the mechanisms how TPH1 possibly contributes to the pathogenesis of psychiatric disorders are not understood. Here, we show an unexpected role of TPH1 in the developing brain. We found that TPH1 is expressed preferentially during the late developmental stage in the mouse brain. TPH1 showed higher affinity to tryptophan and stronger enzyme activity than TPH2 in a condition reflecting that of the developing brainstem. Low 5-HT contents in the raphe nucleus were seen during development in New Zealand white (NZW) and SWR mice having common functional polymorphisms in the<jats:italic>TPH1</jats:italic>gene. However, the 5-HT contents in these mice were not reduced in adulthood. In adult NZW and SWR mice, depression-related behavior was observed. Considering an involvement of developmental brain disturbance in psychiatric disorders, TPH1 may act specifically on development of 5-HT neurons, and thereby influence behavior later in life.</jats:p> Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels The Journal of Neuroscience |
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| title |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_unstemmed |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_full |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_fullStr |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_full_unstemmed |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_short |
Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_sort |
late developmental stage-specific role of tryptophan hydroxylase 1 in brain serotonin levels |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.1835-05.2006 |
| publishDate |
2006 |
| physical |
530-534 |
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<jats:p>Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement in psychiatric conditions and behavioral traits. However,<jats:italic>TPH1</jats:italic>mRNA was reported to be mainly expressed in the pineal gland and the periphery and to be barely detected in the brain. Therefore, contribution of TPH1 to brain 5-HT levels is not known, and the mechanisms how TPH1 possibly contributes to the pathogenesis of psychiatric disorders are not understood. Here, we show an unexpected role of TPH1 in the developing brain. We found that TPH1 is expressed preferentially during the late developmental stage in the mouse brain. TPH1 showed higher affinity to tryptophan and stronger enzyme activity than TPH2 in a condition reflecting that of the developing brainstem. Low 5-HT contents in the raphe nucleus were seen during development in New Zealand white (NZW) and SWR mice having common functional polymorphisms in the<jats:italic>TPH1</jats:italic>gene. However, the 5-HT contents in these mice were not reduced in adulthood. In adult NZW and SWR mice, depression-related behavior was observed. Considering an involvement of developmental brain disturbance in psychiatric disorders, TPH1 may act specifically on development of 5-HT neurons, and thereby influence behavior later in life.</jats:p> |
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| author | Nakamura, Kazuhiro, Sugawara, Yuko, Sawabe, Keiko, Ohashi, Akiko, Tsurui, Hiromichi, Xiu, Yan, Ohtsuji, Mareki, Lin, Qing Shun, Nishimura, Hiroyuki, Hasegawa, Hiroyuki, Hirose, Sachiko |
| author_facet | Nakamura, Kazuhiro, Sugawara, Yuko, Sawabe, Keiko, Ohashi, Akiko, Tsurui, Hiromichi, Xiu, Yan, Ohtsuji, Mareki, Lin, Qing Shun, Nishimura, Hiroyuki, Hasegawa, Hiroyuki, Hirose, Sachiko, Nakamura, Kazuhiro, Sugawara, Yuko, Sawabe, Keiko, Ohashi, Akiko, Tsurui, Hiromichi, Xiu, Yan, Ohtsuji, Mareki, Lin, Qing Shun, Nishimura, Hiroyuki, Hasegawa, Hiroyuki, Hirose, Sachiko |
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| description | <jats:p>Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement in psychiatric conditions and behavioral traits. However,<jats:italic>TPH1</jats:italic>mRNA was reported to be mainly expressed in the pineal gland and the periphery and to be barely detected in the brain. Therefore, contribution of TPH1 to brain 5-HT levels is not known, and the mechanisms how TPH1 possibly contributes to the pathogenesis of psychiatric disorders are not understood. Here, we show an unexpected role of TPH1 in the developing brain. We found that TPH1 is expressed preferentially during the late developmental stage in the mouse brain. TPH1 showed higher affinity to tryptophan and stronger enzyme activity than TPH2 in a condition reflecting that of the developing brainstem. Low 5-HT contents in the raphe nucleus were seen during development in New Zealand white (NZW) and SWR mice having common functional polymorphisms in the<jats:italic>TPH1</jats:italic>gene. However, the 5-HT contents in these mice were not reduced in adulthood. In adult NZW and SWR mice, depression-related behavior was observed. Considering an involvement of developmental brain disturbance in psychiatric disorders, TPH1 may act specifically on development of 5-HT neurons, and thereby influence behavior later in life.</jats:p> |
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| spelling | Nakamura, Kazuhiro Sugawara, Yuko Sawabe, Keiko Ohashi, Akiko Tsurui, Hiromichi Xiu, Yan Ohtsuji, Mareki Lin, Qing Shun Nishimura, Hiroyuki Hasegawa, Hiroyuki Hirose, Sachiko 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1835-05.2006 <jats:p>Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having tryptophan hydroxylating activity were identified. Association studies have revealed possible TPH1 involvement in psychiatric conditions and behavioral traits. However,<jats:italic>TPH1</jats:italic>mRNA was reported to be mainly expressed in the pineal gland and the periphery and to be barely detected in the brain. Therefore, contribution of TPH1 to brain 5-HT levels is not known, and the mechanisms how TPH1 possibly contributes to the pathogenesis of psychiatric disorders are not understood. Here, we show an unexpected role of TPH1 in the developing brain. We found that TPH1 is expressed preferentially during the late developmental stage in the mouse brain. TPH1 showed higher affinity to tryptophan and stronger enzyme activity than TPH2 in a condition reflecting that of the developing brainstem. Low 5-HT contents in the raphe nucleus were seen during development in New Zealand white (NZW) and SWR mice having common functional polymorphisms in the<jats:italic>TPH1</jats:italic>gene. However, the 5-HT contents in these mice were not reduced in adulthood. In adult NZW and SWR mice, depression-related behavior was observed. Considering an involvement of developmental brain disturbance in psychiatric disorders, TPH1 may act specifically on development of 5-HT neurons, and thereby influence behavior later in life.</jats:p> Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels The Journal of Neuroscience |
| spellingShingle | Nakamura, Kazuhiro, Sugawara, Yuko, Sawabe, Keiko, Ohashi, Akiko, Tsurui, Hiromichi, Xiu, Yan, Ohtsuji, Mareki, Lin, Qing Shun, Nishimura, Hiroyuki, Hasegawa, Hiroyuki, Hirose, Sachiko, The Journal of Neuroscience, Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels, General Neuroscience |
| title | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_full | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_fullStr | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_full_unstemmed | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_short | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| title_sort | late developmental stage-specific role of tryptophan hydroxylase 1 in brain serotonin levels |
| title_unstemmed | Late Developmental Stage-Specific Role of Tryptophan Hydroxylase 1 in Brain Serotonin Levels |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.1835-05.2006 |