Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System
Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous dis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/14/1/51 |
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| author | Christopher J. O’Connell Ryan S. Brown Taylor M. Peach Owen D. Traubert Hana C. Schwierling Gabrielle A. Notorgiacomo Matthew J. Robson |
| author_facet | Christopher J. O’Connell Ryan S. Brown Taylor M. Peach Owen D. Traubert Hana C. Schwierling Gabrielle A. Notorgiacomo Matthew J. Robson |
| author_sort | Christopher J. O’Connell |
| collection | DOAJ |
| description | Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications. |
| first_indexed | 2024-03-08T11:03:03Z |
| format | Article |
| id | doaj.art-29a73b0f35e64d30afc6b7f5b9a6f714 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-08T11:03:03Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-29a73b0f35e64d30afc6b7f5b9a6f7142024-01-26T15:24:12ZengMDPI AGBrain Sciences2076-34252024-01-011415110.3390/brainsci14010051Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin SystemChristopher J. O’Connell0Ryan S. Brown1Taylor M. Peach2Owen D. Traubert3Hana C. Schwierling4Gabrielle A. Notorgiacomo5Matthew J. Robson6Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USADivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USADivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USADepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USADivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USACollege of Medicine, University of Cincinnati, Cincinnati, OH 45267, USADivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USATraumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications.https://www.mdpi.com/2076-3425/14/1/51traumatic brain injuryserotonindrug discovery |
| spellingShingle | Christopher J. O’Connell Ryan S. Brown Taylor M. Peach Owen D. Traubert Hana C. Schwierling Gabrielle A. Notorgiacomo Matthew J. Robson Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System Brain Sciences traumatic brain injury serotonin drug discovery |
| title | Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System |
| title_full | Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System |
| title_fullStr | Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System |
| title_full_unstemmed | Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System |
| title_short | Strain in the Midbrain: Impact of Traumatic Brain Injury on the Central Serotonin System |
| title_sort | strain in the midbrain impact of traumatic brain injury on the central serotonin system |
| topic | traumatic brain injury serotonin drug discovery |
| url | https://www.mdpi.com/2076-3425/14/1/51 |
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