Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats
Abstract Background Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understan...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Behavioral and Brain Functions |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12993-025-00270-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850028146454167552 |
|---|---|
| author | Lauren P. Giesler William T. O’Brien Jesse Bain Gershon Spitz Emily J. Jaehne Maarten van den Buuse Sandy R. Shultz Richelle Mychasiuk Stuart J. McDonald |
| author_facet | Lauren P. Giesler William T. O’Brien Jesse Bain Gershon Spitz Emily J. Jaehne Maarten van den Buuse Sandy R. Shultz Richelle Mychasiuk Stuart J. McDonald |
| author_sort | Lauren P. Giesler |
| collection | DOAJ |
| description | Abstract Background Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes. Methods Using a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation. Results Sensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex. Conclusions While the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required. |
| format | Article |
| id | doaj-art-8df265a45d08416e981e8425d2e3d2b6 |
| institution | DOAJ |
| issn | 1744-9081 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Behavioral and Brain Functions |
| spelling | doaj-art-8df265a45d08416e981e8425d2e3d2b62025-08-20T02:59:54ZengBMCBehavioral and Brain Functions1744-90812025-03-0121111210.1186/s12993-025-00270-5Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in ratsLauren P. Giesler0William T. O’Brien1Jesse Bain2Gershon Spitz3Emily J. Jaehne4Maarten van den Buuse5Sandy R. Shultz6Richelle Mychasiuk7Stuart J. McDonald8Department of Neuroscience, Monash UniversityDepartment of Neuroscience, Monash UniversityDepartment of Neuroscience, Monash UniversityDepartment of Neuroscience, Monash UniversityDepartment of Psychology Counselling and Therapy, School of Psychology and Public Health, La Trobe UniversityDepartment of Psychology Counselling and Therapy, School of Psychology and Public Health, La Trobe UniversityDepartment of Neuroscience, Monash UniversityDepartment of Neuroscience, Monash UniversityDepartment of Neuroscience, Monash UniversityAbstract Background Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes. Methods Using a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation. Results Sensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex. Conclusions While the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required.https://doi.org/10.1186/s12993-025-00270-5ConcussionVal66MetBiomarkerMicrogliaNeurofilament lightBehavior |
| spellingShingle | Lauren P. Giesler William T. O’Brien Jesse Bain Gershon Spitz Emily J. Jaehne Maarten van den Buuse Sandy R. Shultz Richelle Mychasiuk Stuart J. McDonald Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats Behavioral and Brain Functions Concussion Val66Met Biomarker Microglia Neurofilament light Behavior |
| title | Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| title_full | Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| title_fullStr | Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| title_full_unstemmed | Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| title_short | Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| title_sort | investigating the role of the brain derived neurotrophic factor val66met polymorphism in repetitive mild traumatic brain injury outcomes in rats |
| topic | Concussion Val66Met Biomarker Microglia Neurofilament light Behavior |
| url | https://doi.org/10.1186/s12993-025-00270-5 |
| work_keys_str_mv | AT laurenpgiesler investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT williamtobrien investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT jessebain investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT gershonspitz investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT emilyjjaehne investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT maartenvandenbuuse investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT sandyrshultz investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT richellemychasiuk investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats AT stuartjmcdonald investigatingtheroleofthebrainderivedneurotrophicfactorval66metpolymorphisminrepetitivemildtraumaticbraininjuryoutcomesinrats |