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      Pulsed electromagnetic field attenuated PTSD-induced failure of conditioned fear extinction

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          Abstract

          Objective(s):

          This study aimed to determine whether exposure to pulsed electromagnetic field (PEMF) can impair behavioral failure as induced by PTSD, and also its possible effects on hippocampal neurogenesis. PEMF was used as a non-invasive therapeutic tool in psychiatry.

          Materials and Methods:

          Male rats were divided into Control-Sham exposed, Control-PEMF, PTSD-Sham exposed, and PTSD-PEMF groups. PTSD rats were conducted by the single prolonged stress procedures and then conditioned by the contextual fear conditioning apparatus. Control rats were only conditioned. Experimental rats were submitted to daily PEMF (7 mT, 30 Hz for 16 min/day, 14 days). Sham-exposed groups were submitted to the turned off PEMF apparatus. Fear extinction, sensitized fear and anxiety, cell density in the hippocampus, and proliferation and survival rate of BrdU-labeled cells were evaluated.

          Results:

          Freezing of PTSD-PEMF rats was significantly lower than PTSD-Sham exposed. In the PTSD-PEMF, center and total crossing in open field, also the percentage of open arms entry and time in the elevated plus maze, significantly increased as compared with PTSD-Sham exposed ( P<0.001). Numbers of CA1, CA3, and DG cells in PTSD-PEMF and Control-Sham exposed groups were significantly more than PTSD-Sham exposed ( P<0.001). There were more BrdU-positive cells in the DG of the PTSD-PEMF as compared with the PTSD-Sham exposed. Qualitative observations showed an increased number of surviving BrdU-positive cells in the PTSD-PEMF as compared with PTSD-Sham exposed.

          Conclusion:

          Using 14-day PEM attenuates the PTSD-induced failure of conditioned fear extinction and exaggerated sensitized fear, and this might be related to the neuroprotective effects of magnetic fields on the hippocampus.

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          Most cited references 47

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          Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells.

          Chronic treatments with selective serotonin reuptake inhibitors (SSRIs) have been shown to increase hippocampal neurogenesis. However, it is not known whether SSRIs impact the maturation and functional integration of newborn neurons. Here we examined the effects of subchronic and chronic fluoxetine on the structural and physiological properties of young granule cells. Our results show that doublecortin-positive immature neurons displayed increased dendritic arborization after chronic fluoxetine treatment. In addition, chronic but not subchronic fluoxetine elicited a decrease in the number of newborn neurons expressing immature markers and a corresponding increase in those expressing mature markers. These results suggest that chronic fluoxetine accelerates the maturation of immature neurons. We also investigated the effects of fluoxetine on a form of neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus. This form of LTP was enhanced by chronic fluoxetine, and ablation of neurogenesis with x-irradiation completely blocked the effects of chronic fluoxetine on LTP. Finally, we demonstrated that the behavioral effect of fluoxetine in the novelty-suppressed feeding test requires chronic administration and is blocked by x-irradiation. These results show that the effects of fluoxetine on LTP and behavior both require neurogenesis and follow a similar delayed time course. The effects of chronic fluoxetine on the maturation and functional properties of young neurons may therefore be necessary for its anxiolytic/antidepressant activity and contribute to its delayed onset of therapeutic efficacy.
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            The functional neuroanatomy of PTSD: a critical review.

            Neuroimaging provides an opportunity to understand core processes that mediate the experience of emotions in healthy individuals as well as dysregulation of these processes in conditions such as posttraumatic stress disorder (PTSD). The first decade of neuroimaging research produced symptom provocation, cognitive activation, and functional connectivity studies that highlighted the role of the medial prefrontal cortex (mPFC), amygdala, sublenticular extended amygdala (SLEA), and hippocampus, in mediating symptom formation in PTSD. There is a growing realization that a number of other psychological processes are relevant to PTSD, and they are emerging as a new focus of neuroimaging research. These include fear conditioning, habituation, and extinction; cognitive-emotional interactions; and self-related and social emotional processing. Neuroimaging findings are reviewed that suggest that the mPFC is implicated in a number of these processes. It is proposed that the mPFC plays a role in the "contextualization" of stimuli, and dysregulation of contextualization processes might play a key role in the generation of PTSD symptoms.
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              A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field.

              The open field test (OFT) is a widely used procedure for examining the behavioral effects of drugs and anxiety. Detailed ethological assessments of animal behavior are lacking. Here we present a detailed ethological assessment of the effects of acute treatment with the benzodiazepines, diazepam (DZ, 1.5mg/kg) and chlordiazepoxide (CDP, 5.0 and 10.0mg/kg), as well as exposure to a non-pharmacological agent, a specific pulsed extremely low frequency magnetic field (MAG) on open field behavior. We examined the duration, frequency and time course of various behaviors (i.e. exploration, walk, rear, stretch attend, return, groom, sit, spin turn, jump and sleep) exhibited by male mice in different regions of a novel open field. Both DZ and CDP consistently reduced the typical anxiety-like behaviors of stretch attend and wall-following (thigmotaxis), along with that of an additional new measure: 'returns', without producing any overall effects on total locomotion. The drugs also differed in their effects. CDP elicited a shift in the locomotor pattern from a 'high explore' to a 'high walk', while DZ mainly elicited alterations in sit and groom. The MAG treatment was repeated twice with both exposures reducing horizontal and vertical (rearing) activity and increasing grooming and spin turns. However, the anxiety-like behaviors of stretch attend and return were marginally reduced by only the first exposure. We conclude that a detailed ethological analysis of the OFT allows not only the detection of specific effects of drugs and non-pharmacological agents (i.e. pulsed magnetic field) on anxiety-like behaviors, but also permits the examination of non-specific effects, in particular those on general activity.
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                Author and article information

                Affiliations
                [1 ]School of Biology, Damghan University, Damghan, Semnan, Iran
                [2 ]Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
                Author notes
                [* ]Corresponding author: Kataneh Abrari. School of Biology, Damghan University, Damghan, Iran. Tel: +98-23 35220242; Fax: +98-2335220223; Email: abrari@du.ac.ir
                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                June 2019
                : 22
                : 6
                : 650-659
                10.22038/ijbms.2019.32576.7797
                6570745

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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