초록 ▼

▶ 섭식행동에 중요한 역할을 할 것으로 추정되는 도파민 수용체 D2R 에 대해 Lenti-viral vector small hairpin RNA(Lenti-shD2R)를 제작, 세포주와 뇌 조직에서 제작된 Lenti-shD2R에 의한 유전자 발현 억제를 확인함
▶정상 쥐 대비 D2R-/- 쥐에서 맛있는 음식에 대한 섭취량 및 선호도가 더 증가되어 있음을 확인함‘
▶ 시상하부의 lateral hypothalamus 부위 특이적인 D2R knockdown을 통해 맛있는 음식에 대한 섭취량을 확인해 본 결과, LH에서는 D2R

▶ 섭식행동에 중요한 역할을 할 것으로 추정되는 도파민 수용체 D2R 에 대해 Lenti-viral vector small hairpin RNA(Lenti-shD2R)를 제작, 세포주와 뇌 조직에서 제작된 Lenti-shD2R에 의한 유전자 발현 억제를 확인함
▶정상 쥐 대비 D2R-/- 쥐에서 맛있는 음식에 대한 섭취량 및 선호도가 더 증가되어 있음을 확인함‘
▶ 시상하부의 lateral hypothalamus 부위 특이적인 D2R knockdown을 통해 맛있는 음식에 대한 섭취량을 확인해 본 결과, LH에서는 D2R knockdown에 따른 특이적 변화는 관찰되지 않고 있음
▶정상 쥐와 D2R-/- 쥐의 시상하부, BNST, CeA 부위에서 MC4R, AgRP와 같은 비만신호조절 인자들의 발현이 맛있는 음식 제공에 따라서 발현이 변화됨을 확인

Abstract ▼

Purpose: The dopamine system is critically implicated in food intake regulation. In order to investigate the involvement of dopamine D2 receptor (D2R) in food reward, we examined the palatable food consumption in wild-type (WT) and D2R knockout (D2R-/-) mice, but also we investigated the effect of s

Purpose: The dopamine system is critically implicated in food intake regulation. In order to investigate the involvement of dopamine D2 receptor (D2R) in food reward, we examined the palatable food consumption in wild-type (WT) and D2R knockout (D2R-/-) mice, but also we investigated the effect of specific knockdown of D2R expression using lentivirus-delivered small hairpin RNA against D2R, in lateral hypothalamus (LH).
Results:
Palatable food consumption was increased in D2R-/- mice with restricted access to palatable food as compared to WT mice.
Knockdown of D2R by delivery of lentivraus-mediated small hairpin RNA into specific brain area was successfully performed.
Knockdown of D2R expression using lentivirus-delivered small hairpin RNA against D2R, in lateral hypothalamus (LH) did not affect the palatable food preference in animals.
D2R-/- mice showed an increase in the expression of melanocortin-4 receptor and AGRP AGouti-Related Peptide) in bed nucleus of the stria terminalis, but also in amygdala, which are known to control reward and regulate also aversive behaviors.
However, another hypothalamic appetite-controlling peptide POMC (Proopiomelanocortin) was not affected with palatable food consumption.
Expected contributions:
From our present study, we can suggest a potential role of D2R in food reward and in compulsive eating behavior.
It will be valuable how D2R can interact with melanocortin-4 receptor and AGRP AGouti-Related Peptide) in bed nucleus of the stria terminalis, but also in amygdala, which may be rlated with palatable food preference.
These lines of study will provide us how the brain circuit of binge eating behavior which can lead to obesity in association with eating disorders.