[논문]쥐오줌풀 추출물이 MIA동물모델에서의 신경발달 단백질의 발현과 행동증상에 미치는 영향

원한솔; 김영옥; 이화영; 임지윤; 이상현; 조익현; 이상원; 박춘근; 김형기; 권준택; 김학재

doi:10.7783/kjmcs.2016.24.5.341

쥐오줌풀 추출물이 MIA동물모델에서의 신경발달 단백질의 발현과 행동증상에 미치는 영향
Effect of Valeriana fauriei Extract on the Neurodevelopmental Proteins Expression and Behavioral Patterns in Maternal Immune Activation Animal Model 원문보기

韓國藥用作物學會誌 = Korean journal of medicinal crop science, v.24 no.5, 2016년, pp.341 - 350

원한솔 (순천향대학교 의과대학 임상약리학교실) , 김영옥 (농촌진흥청 국립원예특작과학원 인삼특작부) , 이화영 (순천향대학교 의과대학 임상약리학교실) , 임지윤 (순천향대학교 의과대학 임상약리학교실) , 이상현 (중앙대학교 생명공학대학 식물시스템과학과) , 조익현 (경희대학교 한의과대학 융합의과학교실) , 이상원 (농촌진흥청 국립원예특작과학원 인삼특작부) , 박춘근 (농촌진흥청 국립원예특작과학원 인삼특작부) , 김형기 (순천향대학교 의과대학 임상약리학교실) , 권준택 (순천향대학교 의과대학 임상약리학교실) , 김학재 (순천향대학교 의과대학 임상약리학교실)

Abstract ▼ AI-Helper

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5 mg/kg, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100 mg/kg) and injections of clozapine (5 mg/kg) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIA-induced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.

주제어

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문제 정의

Therefore, the objective of this study was to determine the effect of VF administration on behavioral symptoms and the expression of neurodevelopmental proteins in a MIA model.

가설 설정

In the present study, the typical antipsychotic clozapine was effective in restoring PPI deficits observed in MIA offspring treated with Poly I:C during pregnancy. In this study, we investigated the levels of two proteins; Dpysl2 and neurofilament protein. The decrease of mPFC in neurofilament and Dpysl2 proteins due to MIA was affected by VF treatment.
, 2004). In this study, we proposed that VF might be able to reverse schizophrenia-like behavior in MIA offspring using an animal model.

제안 방법

Background noise of 68 dB was present throughout the test session. After a 5 min acclimation period to the background noise, trials were presented in pseudorandom order, including 14 pulse alone trials in which a 40ms, 120dB broadband noise burst was presented, 30 prepulse + pulse trials in which the onset of a 20ms broadband noise prepulse preceded the onset of the 120 dB pulse by 100ms (10 for each of prepulse intensities of 3, 6, and 12 dB above the background noise, respectively), and eight non-stimulus trials consisting of only background noise. Prepulse intensities used in our protocol did not induce startle reaction.
All trials were presented with an average inter-trial interval of 22 s (15 - 30 s range). Four 120 dB pulse trials were presented at the beginning and the end of the test session with a series of 60 acoustic stimuli trials. However, they were not used in the calculation of PPI values.

대상 데이터

C57BL6/J mice (8 weeks old) were purchased from Central Lab Animal Inc. (Seoul, Korea). Mice were mated in groups of 1 male and 2 females.
The VF was obtained from a local farm in Jingbu province Republic of Korea. The roots of VF were airdried avoiding sun-light and cut into small pieces for the experiment.
The test was carried out in clear opaque Plexiglas boxes (50 ㎝ × 50 ㎝ × 25 ㎝) equipped with a video as described previously (Cryan and Mombereau, 2004).

데이터처리

They were compared using Student’s t-test.

이론/모형

We tested whether clozapine and VF treatment might be effective in preventing emergence of sensorimotor gating deficiency following MIA during adulthood. Sensorimotor gating was evaluated using the paradigm of PPI of acoustic startle reflex (ASR). Peripubertal clozapine and VF administration prevented the disruption of PPI in the offspring exposed to MIA (p < 0.

성능/효과

Immunofluorescent-stained brain images revealed that Dpysl2 and Nefm were differentially expressed among control, MIA, clozapine treated, and VF treated groups with significant differences in staining intensity value (p < 0.05, Fig. 4, 5).
Our results indicated that MIA significantly (p < 0.05) altered PPI level at prepulse stimulus levels of 6, 9, and 12 dB above background between MIA offspring and control offspring.
Our results showed that maternal administration of Poly I:C into MIA caused abnormality of behavioral pattern, deficits in sensory-motor gating, and aggressive behavior in SIT. However, these effects could be improved by oral administration extract of VF.

후속연구

The present study provided valuable data regarding additional role of VF in addressing the pathogenesis of psychiatric disorders such as schizophrenia. However, further research is needed to characterize the pharmacological functions of VF using cellular and animal models.

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저자의 다른 논문 :

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동의어: Packet Collision Rate

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