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Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats

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Abstract

Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.

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Acknowledgements

Research was sponsored by the US Army Research Office and the Defense Advanced Research Projects Agency (DARPA) and was accomplished under Cooperative Agreement Number W911NF-14-2-0100.

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  1. Taiza H. Figueiredo and Carolina L. Harbert contributed equally to this work

Authors and Affiliations

  1. Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA

    Taiza H. Figueiredo, Carolina L. Harbert, Volodymyr Pidoplichko, Camila P. Almeida-Suhett, Katia Rossetti & Maria F. M. Braga

  2. Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA

    Hongna Pan & Ann M. Marini

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  1. Taiza H. Figueiredo
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Figueiredo, T.H., Harbert, C.L., Pidoplichko, V. et al. Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats. Mol Neurobiol 55, 187–200 (2018). https://doi.org/10.1007/s12035-017-0732-y

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