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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Autores principales:	Sascha R. A. Alles, Max A. Odem, Van B. Lu, Ryan M. Cassidy, Peter A. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e69283edd694e9888f90e726ca6e55a
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spelling	oai:doaj.org-article:3e69283edd694e9888f90e726ca6e55a2021-12-02T14:16:16ZChronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity10.1038/s41598-021-81269-62045-2322https://doaj.org/article/3e69283edd694e9888f90e726ca6e55a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81269-6https://doaj.org/toc/2045-2322Abstract 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.Sascha R. A. AllesMax A. OdemVan B. LuRyan M. CassidyPeter A. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Sascha R. A. Alles Max A. Odem Van B. Lu Ryan M. Cassidy Peter A. Smith
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 Portfolio
publishDate	2021
url	https://doaj.org/article/3e69283edd694e9888f90e726ca6e55a
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Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity

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