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

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C Yoo

C Yoo1*, K Song1 , S Lim1 , B Choe1 , (1) The Catholic University of Korea, Seoul, Korea

Presentations

MO-L-GePD-IT-4 (Monday, July 31, 2017) 1:15 PM - 1:45 PM Room: Imaging ePoster Theater


Purpose: Repeated exposure to 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 the disease-induced metabolic alterations. The purpose of this study was to investigate neurometabolic alteration in prefrontal cortex (PFC) with respect to progression of schizophrenia by using in vivo ¹H MRS.

Methods: High-field ¹H MRS was used to measure the neurometabolic levels in the PFC of the rats (n = 13) before and after the 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 voxel that was carefully located in the PFC with parameters like follow; repetition time, 5000ms; echo time (TE), 13.4 ms; spectral bandwidth, 5000 Hz; averages, 256.

Results: At the day-6 MRI/MRS examinations, stereotyped behaviors were observed in all rats. Figs 1, 2 show representative MR images and in vivo ¹H MR spectra. Significant (p < 0.05) concentration changes between the two times were not observed. However, changes in Glu and NAA levels were significantly correlated (Figure 3). As illustrated in Figure 4, half of the rats (n = 7) showed increases of Glu and NAA (a), and the others (n = 6) showed decreases (b). These metabolic alterations were consistent with the results of patients with first-episode and chronic schizophrenia, respectively.

Conclusion: From our findings, repeated exposure to MK-801 could provide a pathophysiological insight into the transition from first-episode to chronic schizophrenia. With high-field in vivo 1H MRS, up to 20 brain neurometabolites could be reliably measured. We expect that our findings can contribute to the insights into the progression of SZ.


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