Ketogenic diet prevents impaired prepulse inhibition of startle in an acute NMDA receptor hypofunction model of schizophrenia

Kraeuter, Ann-Katrin, van den Buuse, Maarten, and Sarnyai, Zoltán (2018) Ketogenic diet prevents impaired prepulse inhibition of startle in an acute NMDA receptor hypofunction model of schizophrenia. Schizophrenia Research. (In Press)

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Abstract

Recent transcriptomic, proteomic and metabolomics studies have highlighted an abnormal cerebral glucose and energy metabolism as one of the potential pathophysiological mechanisms of schizophrenia. This raises the possibility that a metabolically-based intervention might have therapeutic value in the management of schizophrenia, a notion supported by our recent results that a low carbohydrate/high-fat therapeutic ketogenic diet (KD) prevented a variety of behavioural abnormalities induced by pharmacological inhibition of NMDA glutamate receptors. Here we asked if the beneficial effects of KD can be generalised to impaired prepulse inhibition of startle (PPI), a translationally validated endophenotype of schizophrenia, in a pharmacological model in mice. Furthermore, we addressed the issue of whether the effect of KD is linked to the calorie-restricted state typical of the initial phase of KD. We fed male C57BL/6 mice a KD for 7 weeks and tested PPI at 3 and 7 weeks, in the presence and absence of a significant digestible energy deficit, respectively. We used an NMDA receptor hypo-function model of schizophrenia induced by acute injection of dizocilpine (MK-801). We found that KD effectively prevented MK-801-induced PPI impairments at both 3 and 7 weeks, irrespective of the presence or absence of digestible energy deficit. Furthermore, there was a lack of correlation between PPI and body weight changes. These results support the efficacy of the therapeutic KD in a translational model of schizophrenia and furthermore provide evidence against the role of calorie restriction in its mechanism of action.

Item ID: 57136
Item Type: Article (Research - C1)
ISSN: 1573-2509
Keywords: schizophrenia; ketogenic diet; sensorimotor gating; glucose metabolism; energy; β-Hydroxybutyrate
Copyright Information: Copyright © 2018 Elsevier B.V. All rights reserved.
Funders: James Cook University (JCU), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: JCU Postgraduate Research Scholarship, JCU Higher Degree Research Enhancement Funding Scheme, NHMRC Senior Research Fellowship
Date Deposited: 18 Feb 2019 22:22
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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