Striatal damage may underlie motor learning impairment following experimental mild traumatic brain injury in mice
Caroline Amaral Machado1, Bruna da Silva Oliveira1, Heliana de Barros Fernandes1
1Laboratório de Neurobiologia, Departamento de Morfologia, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, MG, Brazil.
Abstract:
The Renin-Angiotensin system (RAS) has receptors in key brain areas, including the striatum, and has been implicated in traumatic brain injury (TBI) outcomes through involvement in inflammation and oxidative stress. To date, whether striatal RAS dysregulation alongside inflammatory response and oxidative stress underlie mild TBI-related motor coordination and learning impairments remain to be explored. Herein, we employed a weight drop model to induce mild TBI (mTBI) in mice and investigate striatal damage at 72 h after the trauma. mTBI mice displayed significant decrease in the motor learning index and increase in the latency to fall in the rotarod compared with sham controls. In parallel, mTBI-mice had increased expression of RAS classical arm components AT1 and AT2 receptors along with a decrease in RAS counter-regulatory component Mas receptor in the ipsilateral striatum. The neurotrophic factor GDNF increased and the chemokine CX3CL1 decreased in the ipsilateral striatum while TNF-α enhanced in the contralateral striatum at 72 h after mTBI. Higher lipid peroxidation (TBARS) levels were found in both ipsilateral and contralateral striatum of mTBI mice compared with sham mice. We provided original evidence that changes in RAS, inflammatory, neurotrophic and oxidative stress responses in the striatum may contribute to motor dysfunction following acute mTBI.
Insights
Mild traumatic brain injury (mTBI) disrupts the brain's Renin-Angiotensin system (RAS) and increases oxidative stress, leading to motor coordination and learning deficits. These changes in the striatum contribute to functional impairments after brain injury.
Area of Science:
- Neuroscience
- Neurotrauma
- Molecular Biology
Background:
- The Renin-Angiotensin system (RAS) is present in brain regions like the striatum.
- RAS involvement in inflammation and oxidative stress suggests a role in traumatic brain injury (TBI) outcomes.
- The specific contribution of striatal RAS, inflammation, and oxidative stress to mild TBI (mTBI)-induced motor and learning deficits is not well understood.
Purpose of the Study:
- To investigate the role of striatal RAS, inflammation, and oxidative stress in motor and learning impairments following mTBI.
- To examine changes in RAS components, inflammatory markers, neurotrophic factors, and oxidative stress in the mouse striatum at 72 hours post-mTBI.
Main Methods:
- A weight drop model was used to induce mTBI in mice.
- Motor function was assessed using the rotarod test and a motor learning index.
- Expression of RAS receptors (AT1, AT2, Mas), GDNF, CX3CL1, and TNF-α were measured.
- Lipid peroxidation (TBARS) was quantified to assess oxidative stress.
Main Results:
- mTBI mice showed impaired motor learning and reduced latency to fall on the rotarod.
- Increased AT1 and AT2 receptor expression and decreased Mas receptor expression were observed in the ipsilateral striatum.
- GDNF levels increased, CX3CL1 decreased in the ipsilateral striatum, and TNF-α increased in the contralateral striatum.
- Elevated TBARS levels indicated increased lipid peroxidation in both striata of mTBI mice.
Conclusions:
- Striatal RAS dysregulation, altered inflammatory responses, and increased oxidative stress are associated with motor dysfunction after acute mTBI.
- These molecular and cellular changes in the striatum may underlie the observed motor coordination and learning deficits following mild TBI.
