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      β-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD

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          Abstract

          This study investigated the effects of β-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg −1) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher ( p < 0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater ( p < 0.05) in animals exposed to PSS compared to animals unexposed. CS expression was higher ( p < 0.05) in animals exposed to PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower ( p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

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          Most cited references41

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          Diagnostic and statistical manual of mental disorders.

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            Neurons in medial prefrontal cortex signal memory for fear extinction.

            Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
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              Stress and hippocampal plasticity.

              B S McEwen (1999)
              The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.
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                Author and article information

                Contributors
                407-823-1272 , jay.hoffman@ucf.edu
                Journal
                Amino Acids
                Amino Acids
                Amino Acids
                Springer Vienna (Vienna )
                0939-4451
                1438-2199
                11 March 2015
                11 March 2015
                2015
                : 47
                : 1247-1257
                Affiliations
                [ ]Institute of Exercise Physiology and Wellness, Sport and Exercise Science, University of Central Florida, Orlando, FL 32816 USA
                [ ]Israel Defense Force, Medical Corps, Tel Hashomer, Israel
                [ ]Junipa Ltd, Newmarket, UK
                [ ]Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Faculty of Health Sciences, Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel
                Author notes

                Handling Editor: G. Lubec.

                Article
                1952
                10.1007/s00726-015-1952-y
                4429141
                25758106
                148ca6b2-4620-444e-be79-6a144b07ca6b
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 23 February 2015
                : 25 February 2015
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag Wien 2015

                Genetics
                supplementation,carnosine,military,nutrition,bdnf,corticosterone
                Genetics
                supplementation, carnosine, military, nutrition, bdnf, corticosterone

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