Citation

Figueiredo TH, Harbert CL, Pidoplichko V, Almeida-Suhett CP, Pan H, Rossetti K, Braga MFM, Marini AM. Mol. Neurobiol. 2018; 55(1): 187-200.

Affiliation

Department of Neurology and Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. ann.marini@usuhs.edu.

Copyright

(Copyright © 2018, Springer)

DOI

10.1007/s12035-017-0732-y

PMID

28844093

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.

Language: en

Keywords

Alpha-linolenic acid; Anxiety disorders; Controlled cortical impact; Rat; Traumatic brain injury