Amelioration of behavioral abnormalities in BH4-deficient mice by dietary supplementation of tyrosine티로신 식이요법에 의한 BH4-결핍 생쥐의 행동적응이상의 개선

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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 was severely suppressed in brains of Spr-/- mice fed a normal diet but 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.
Advisors
Joe, Cheol-Oresearcher조철오
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2013
Identifier
565540/325007  / 020075332
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2013.8, [ v, 81 p. ]

Keywords

Tetrahydrobiopterin; mTOR복합체1; 도파민; 티로신; 세피어프테린 환원효소; 테트라히드로비옵테린; Sepiapterin reductase; Tyrosine; Dopamine; mTORC1

URI
http://hdl.handle.net/10203/196200
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=565540&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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