Cargando…

The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic–pituitary–adrenal (HPA) axis either by primary injury to the hypothalamic–hypophyseal region or by secondary vascular damage, brain, an...

Descripción completa

Detalles Bibliográficos
Autores principales: Taheri, Serpil, Karaca, Züleyha, Mehmetbeyoglu, Ecmel, Hamurcu, Zuhal, Yilmaz, Zeynep, Dal, Fatma, Çınar, Venhar, Ulutabanca, Halil, Tanriverdi, Fatih, Unluhizarci, Kursad, Rassoulzadegan, Minoo, Kelestimur, Fahrettin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778890/
https://www.ncbi.nlm.nih.gov/pubmed/36555341
http://dx.doi.org/10.3390/ijms232415699
_version_ 1784856474710704128
author Taheri, Serpil
Karaca, Züleyha
Mehmetbeyoglu, Ecmel
Hamurcu, Zuhal
Yilmaz, Zeynep
Dal, Fatma
Çınar, Venhar
Ulutabanca, Halil
Tanriverdi, Fatih
Unluhizarci, Kursad
Rassoulzadegan, Minoo
Kelestimur, Fahrettin
author_facet Taheri, Serpil
Karaca, Züleyha
Mehmetbeyoglu, Ecmel
Hamurcu, Zuhal
Yilmaz, Zeynep
Dal, Fatma
Çınar, Venhar
Ulutabanca, Halil
Tanriverdi, Fatih
Unluhizarci, Kursad
Rassoulzadegan, Minoo
Kelestimur, Fahrettin
author_sort Taheri, Serpil
collection PubMed
description Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic–pituitary–adrenal (HPA) axis either by primary injury to the hypothalamic–hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic–pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.
format Online
Article
Text
id pubmed-9778890
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97788902022-12-23 The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI) Taheri, Serpil Karaca, Züleyha Mehmetbeyoglu, Ecmel Hamurcu, Zuhal Yilmaz, Zeynep Dal, Fatma Çınar, Venhar Ulutabanca, Halil Tanriverdi, Fatih Unluhizarci, Kursad Rassoulzadegan, Minoo Kelestimur, Fahrettin Int J Mol Sci Article Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic–pituitary–adrenal (HPA) axis either by primary injury to the hypothalamic–hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic–pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI. MDPI 2022-12-10 /pmc/articles/PMC9778890/ /pubmed/36555341 http://dx.doi.org/10.3390/ijms232415699 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Taheri, Serpil
Karaca, Züleyha
Mehmetbeyoglu, Ecmel
Hamurcu, Zuhal
Yilmaz, Zeynep
Dal, Fatma
Çınar, Venhar
Ulutabanca, Halil
Tanriverdi, Fatih
Unluhizarci, Kursad
Rassoulzadegan, Minoo
Kelestimur, Fahrettin
The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title_full The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title_fullStr The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title_full_unstemmed The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title_short The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)
title_sort role of apoptosis and autophagy in the hypothalamic-pituitary-adrenal (hpa) axis after traumatic brain injury (tbi)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778890/
https://www.ncbi.nlm.nih.gov/pubmed/36555341
http://dx.doi.org/10.3390/ijms232415699
work_keys_str_mv AT taheriserpil theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT karacazuleyha theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT mehmetbeyogluecmel theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT hamurcuzuhal theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT yilmazzeynep theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT dalfatma theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT cınarvenhar theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT ulutabancahalil theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT tanriverdifatih theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT unluhizarcikursad theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT rassoulzadeganminoo theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT kelestimurfahrettin theroleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT taheriserpil roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT karacazuleyha roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT mehmetbeyogluecmel roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT hamurcuzuhal roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT yilmazzeynep roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT dalfatma roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT cınarvenhar roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT ulutabancahalil roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT tanriverdifatih roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT unluhizarcikursad roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT rassoulzadeganminoo roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi
AT kelestimurfahrettin roleofapoptosisandautophagyinthehypothalamicpituitaryadrenalhpaaxisaftertraumaticbraininjurytbi