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...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15699 |
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| author | Serpil Taheri Züleyha Karaca Ecmel Mehmetbeyoglu Zuhal Hamurcu Zeynep Yilmaz Fatma Dal Venhar Çınar Halil Ulutabanca Fatih Tanriverdi Kursad Unluhizarci Minoo Rassoulzadegan Fahrettin Kelestimur |
| author_facet | Serpil Taheri Züleyha Karaca Ecmel Mehmetbeyoglu Zuhal Hamurcu Zeynep Yilmaz Fatma Dal Venhar Çınar Halil Ulutabanca Fatih Tanriverdi Kursad Unluhizarci Minoo Rassoulzadegan Fahrettin Kelestimur |
| author_sort | Serpil Taheri |
| collection | DOAJ |
| 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 (<i>Lc3</i>, <i>Bcln1</i>, <i>P150</i>, <i>Ulk</i>, and <i>Atg5</i>) 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. |
| first_indexed | 2024-03-09T16:20:02Z |
| format | Article |
| id | doaj.art-c4d9b10f07eb4e328e0b43a3dcca9bd3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:20:02Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c4d9b10f07eb4e328e0b43a3dcca9bd32023-11-24T15:26:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241569910.3390/ijms232415699The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)Serpil Taheri0Züleyha Karaca1Ecmel Mehmetbeyoglu2Zuhal Hamurcu3Zeynep Yilmaz4Fatma Dal5Venhar Çınar6Halil Ulutabanca7Fatih Tanriverdi8Kursad Unluhizarci9Minoo Rassoulzadegan10Fahrettin Kelestimur11Department of Medical Biology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyDepartment of Endocrinology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyBetul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38030 Kayseri, TurkeyDepartment of Medical Biology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyDepartment of Medical Biology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyBetul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38030 Kayseri, TurkeyDepartment of Medical Biology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyDepartment of Neurosurgery, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyDepartment of Endocrinology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyDepartment of Endocrinology, Medical Faculty, Erciyes University, 38030 Kayseri, TurkeyBetul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38030 Kayseri, TurkeyDepartment of Endocrinology, Medical Faculty, Yeditepe University, 34755 Istanbul, TurkeyTraumatic 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 (<i>Lc3</i>, <i>Bcln1</i>, <i>P150</i>, <i>Ulk</i>, and <i>Atg5</i>) 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.https://www.mdpi.com/1422-0067/23/24/15699traumatic brain injury (TBI)inflammationHPA axisautophagyapoptosis |
| spellingShingle | Serpil Taheri Züleyha Karaca Ecmel Mehmetbeyoglu Zuhal Hamurcu Zeynep Yilmaz Fatma Dal Venhar Çınar Halil Ulutabanca Fatih Tanriverdi Kursad Unluhizarci Minoo Rassoulzadegan Fahrettin Kelestimur The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI) International Journal of Molecular Sciences traumatic brain injury (TBI) inflammation HPA axis autophagy apoptosis |
| 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 | traumatic brain injury (TBI) inflammation HPA axis autophagy apoptosis |
| url | https://www.mdpi.com/1422-0067/23/24/15699 |
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