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Impaired Energy Metabolism and Disturbed Dopamine and Glutamate Signalling in the Striatum and Prefrontal Cortex of the Spontaneously Hypertensive Rat Model of Attention-Deficit Hyperactivity Disorder

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Abstract

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous behavioural disorder that affects 3–15 % of children worldwide. Spontaneously hypertensive rats (SHR) display the major symptoms of ADHD (hyperactivity, impulsivity and poor performance in tasks that require sustained attention) and are widely used to model the disorder. The present study aimed to test the hypothesis that SHR have a diminished capacity to generate ATP required for rapid synchronized neuronal firing, failure of which might lead to disturbances in neurotransmission that could contribute to their ADHD-like behaviour. Duplicate pooled (n = 5) samples of prefrontal cortex and striatum of prepubertal (35-day-old) SHR and Wistar Kyoto (WKY) rats were subjected to iTRAQ labeling and matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS). The MS/MS spectra were analyzed with ProteinPilot using the Ratus ratus database. Proteins detected with >95 % confidence were tested. SHR had decreased levels of several proteins involved in energy metabolism, cytoskeletal structure, myelination and neurotransmitter function when compared to WKY. Differences in protein levels between SHR and WKY were similar in prefrontal cortex and striatum, suggesting global changes in cortico-striato-thalamo-cortical circuits.

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Acknowledgments

The authors wish to thank the Medical Research Council and the University of Cape Town for the financial support and the Centre for Proteomic and Genomic Research for the proteomic analyses.

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Authors and Affiliations

  1. Department of Human Biology, University of Cape Town, Observatory, Cape Town, 7925, South Africa

    Jacqueline J. Dimatelis, Jennifer H. Hsieh, Toni-Lee Sterley, Lelanie Marais, Jacqueline S. Womersley & Vivienne A. Russell

  2. Centre for Proteomic and Genomic Research, Observatory, Cape Town, 7925, South Africa

    Maré Vlok

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  1. Jacqueline J. Dimatelis
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  2. Jennifer H. Hsieh
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  3. Toni-Lee Sterley
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Correspondence to Jacqueline J. Dimatelis.

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Dimatelis, J.J., Hsieh, J.H., Sterley, TL. et al. Impaired Energy Metabolism and Disturbed Dopamine and Glutamate Signalling in the Striatum and Prefrontal Cortex of the Spontaneously Hypertensive Rat Model of Attention-Deficit Hyperactivity Disorder. J Mol Neurosci 56, 696–707 (2015). https://doi.org/10.1007/s12031-015-0491-z

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  • DOI: https://doi.org/10.1007/s12031-015-0491-z

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