Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity
Abstract Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5–6 ...
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2021-01-01
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doaj-3e69283edd694e9888f90e726ca6e55a2021-01-31T16:21:06ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111410.1038/s41598-021-81269-6Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activitySascha R. A. Alles0Max A. Odem1Van B. Lu2Ryan M. Cassidy3Peter A. Smith4Department of Anesthesiology & Critical Care Medicine, University of New Mexico Health Sciences CenterDepartment of Microbiology and Molecular Genetics, McGovern Medical School at UTHealthNeuroscience and Mental Health Institute & Department of Pharmacology, University of AlbertaDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical CenterNeuroscience and Mental Health Institute & Department of Pharmacology, University of AlbertaAbstract Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5–6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of ‘silent’ neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.https://doi.org/10.1038/s41598-021-81269-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sascha R. A. Alles Max A. Odem Van B. Lu Ryan M. Cassidy Peter A. Smith |
spellingShingle |
Sascha R. A. Alles Max A. Odem Van B. Lu Ryan M. Cassidy Peter A. Smith Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity Scientific Reports |
author_facet |
Sascha R. A. Alles Max A. Odem Van B. Lu Ryan M. Cassidy Peter A. Smith |
author_sort |
Sascha R. A. Alles |
title |
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
title_short |
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
title_full |
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
title_fullStr |
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
title_full_unstemmed |
Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
title_sort |
chronic bdnf simultaneously inhibits and unmasks superficial dorsal horn neuronal activity |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-01-01 |
description |
Abstract Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5–6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of ‘silent’ neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF. |
url |
https://doi.org/10.1038/s41598-021-81269-6 |
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