Date of Presentation
5-2-2024 12:00 AM
College
Rowan-Virtua School of Osteopathic Medicine
Poster Abstract
It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following rmTBI has not.
To investigate this gap, we used the closed head-controlled cortical impact model to induce 3 mild injuries in Long Evans rats of both sexes. Rats received either saline or MPH (2mg/kg) daily for 7 days (4 groups; sham/saline, sham/MPH, rmTBI/saline, rmTBI/MPH). Brain tissue from the medial (mPFC) and orbitofrontal (OFC) regions of the PFC were collected and standard western blotting protocols were used to measure protein levels of NET, tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), catechol-O-methyltransferase (COMT) and monoamine oxidase (MOA). Within the mPFC, female NET and VMAT levels were decreased in the rmTBI/saline group, while the rmTBI/MPH group’s protein levels did not differ from controls. In males, mPFC VMAT levels were decreased in both rmTBI groups. Within the OFC, NET and VMAT levels were decreased in the male rmTBI/MPH group only.
These results suggest that rmTBI reduces transporter levels within regions of the PFC and that sub-chronic MPH treatment may produce restorative benefits on these protein levels in female, but not male rodents following rmTBI. We conclude that interactions between rmTBI and MPH on levels of catecholamine regulatory proteins may begin to elucidate sex differential changes in risk-taking behavior following injury and treatment.
Keywords
TBI, MPH, NET, VMAT, concussion, traumatic brain, Vesicular Monoamine Transport Proteins injury, methylphenidate, rats, male
Disciplines
Behavioral Neurobiology | Disease Modeling | Laboratory and Basic Science Research | Medical Neurobiology | Medicine and Health Sciences | Neurology | Pathological Conditions, Signs and Symptoms | Physiological Processes
Document Type
Poster
Included in
Behavioral Neurobiology Commons, Disease Modeling Commons, Laboratory and Basic Science Research Commons, Medical Neurobiology Commons, Neurology Commons, Pathological Conditions, Signs and Symptoms Commons, Physiological Processes Commons
Interactions Between Repetitive Mild Traumatic Brain Injury and Methylphenidate Administration on Catecholamine Transporter Protein Levels Within the Rodent Prefrontal Cortex
It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following rmTBI has not.
To investigate this gap, we used the closed head-controlled cortical impact model to induce 3 mild injuries in Long Evans rats of both sexes. Rats received either saline or MPH (2mg/kg) daily for 7 days (4 groups; sham/saline, sham/MPH, rmTBI/saline, rmTBI/MPH). Brain tissue from the medial (mPFC) and orbitofrontal (OFC) regions of the PFC were collected and standard western blotting protocols were used to measure protein levels of NET, tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), catechol-O-methyltransferase (COMT) and monoamine oxidase (MOA). Within the mPFC, female NET and VMAT levels were decreased in the rmTBI/saline group, while the rmTBI/MPH group’s protein levels did not differ from controls. In males, mPFC VMAT levels were decreased in both rmTBI groups. Within the OFC, NET and VMAT levels were decreased in the male rmTBI/MPH group only.
These results suggest that rmTBI reduces transporter levels within regions of the PFC and that sub-chronic MPH treatment may produce restorative benefits on these protein levels in female, but not male rodents following rmTBI. We conclude that interactions between rmTBI and MPH on levels of catecholamine regulatory proteins may begin to elucidate sex differential changes in risk-taking behavior following injury and treatment.