Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine.
This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4)-deficient Spr (-/-) mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3618182?pdf=render |
| _version_ | 1798045556998668288 |
|---|---|
| author | Sang Su Kwak Mikyoung Jeong Ji Hye Choi Daesoo Kim Hyesun Min Yoosik Yoon Onyou Hwang Gary G Meadows Cheol O Joe |
| author_facet | Sang Su Kwak Mikyoung Jeong Ji Hye Choi Daesoo Kim Hyesun Min Yoosik Yoon Onyou Hwang Gary G Meadows Cheol O Joe |
| author_sort | Sang Su Kwak |
| collection | DOAJ |
| description | This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4)-deficient Spr (-/-) mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr (-/-) mice. We found that Spr (-/-) mice display variable 'open-field' behaviors, impaired motor functions on the 'rotating rod', and dystonic 'hind-limb clasping'. In this study, we report that these aberrant motor deficits displayed by Spr (-/-) mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr (-/-) mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA) and its metabolites in Spr (-/-) mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr (-/-) mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency. |
| first_indexed | 2024-04-11T23:22:53Z |
| format | Article |
| id | doaj.art-18c8cbd401434201a96802813f866fd9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:22:53Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-18c8cbd401434201a96802813f866fd92022-12-22T03:57:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6080310.1371/journal.pone.0060803Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine.Sang Su KwakMikyoung JeongJi Hye ChoiDaesoo KimHyesun MinYoosik YoonOnyou HwangGary G MeadowsCheol O JoeThis study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4)-deficient Spr (-/-) mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr (-/-) mice. We found that Spr (-/-) mice display variable 'open-field' behaviors, impaired motor functions on the 'rotating rod', and dystonic 'hind-limb clasping'. In this study, we report that these aberrant motor deficits displayed by Spr (-/-) mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr (-/-) mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA) and its metabolites in Spr (-/-) mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr (-/-) mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency.http://europepmc.org/articles/PMC3618182?pdf=render |
| spellingShingle | Sang Su Kwak Mikyoung Jeong Ji Hye Choi Daesoo Kim Hyesun Min Yoosik Yoon Onyou Hwang Gary G Meadows Cheol O Joe Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. PLoS ONE |
| title | Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. |
| title_full | Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. |
| title_fullStr | Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. |
| title_full_unstemmed | Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. |
| title_short | Amelioration of behavioral abnormalities in BH(4)-deficient mice by dietary supplementation of tyrosine. |
| title_sort | amelioration of behavioral abnormalities in bh 4 deficient mice by dietary supplementation of tyrosine |
| url | http://europepmc.org/articles/PMC3618182?pdf=render |
| work_keys_str_mv | AT sangsukwak ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT mikyoungjeong ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT jihyechoi ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT daesookim ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT hyesunmin ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT yoosikyoon ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT onyouhwang ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT garygmeadows ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine AT cheolojoe ameliorationofbehavioralabnormalitiesinbh4deficientmicebydietarysupplementationoftyrosine |