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Neurometabolic Effect Induced by Repeated Exposure to Dizocilpine On Prefrontal Cortex of Schizophrenic Animal Model Using In Vivo Proton Magnetic Resonance Spectroscopy at 9.4 T

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C Yoo

C-H Yoo1,2*, K-H Song1, S-I Lim1,2, D-C Woo2, B-Y Choe1 , (1) Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Korea , (2) Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea

Presentations

SU-F-I-67 (Sunday, July 31, 2016) 3:00 PM - 6:00 PM Room: Exhibit Hall


Purpose: Repeated exposure of dizocilpine (MK-801) can provide a pathophysiological model for progressive development of schizophrenia. In vivo proton magnetic resonance spectroscopy (¹H MRS) was widely used for non-invasive measurement of neurometabolites, and assessment of disease-induced neurometabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression (from first-episode to chronic stage) of schizophrenia by using in vivo ¹H MRS.

Methods: We used high-field ¹H MRS to investigate the neurometabolic alteration in the PFC region of the rats (N = 13) by comparing before and after 6 day of MK-801 (0.5 mg/kg) treatment. A point-resolved spectroscopy (PRESS) sequence was used to obtain spectra in a 22.5 μL of volume of interest carefully located in PFC region with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; averages = 256. Another experiment group (N = 11) were conducted behavior test by recording the behavior for 20 min.

Results: All the rats showed hyperlocomotion, stereotyped behaviors before initiation of MRS. Significantly increased level (N = 7, p < 0.05) of N-acetylasrparate (NAA), glutamate (Glu), taurine and decreased level (N = 6, p < 0.05) of NAA, Glu and phosphocreatine were observed between baseline and day 6. Both metabolic alterations are consistent with results of first-episode and chronic schizophrenia respectively.

Conclusions: From our findings, the repeated MK-801 model could be a pathophysiological model which can provide an insight into the transition from first-episode to chronic stage. This is first time to investigate effects of repeated MK-801 using high-field in vivo ¹H MRS. We expect our findings can contribute to combining previous diverging results into one pathophysiological interpretation, which can postulate the origin of diverging results to the progression of schizophrenia.



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