Changes in dopamine transporter expression in the midbrain following traumatic brain injury: an immunohistochemical and in situ hybridization study in a mouse model

Abstract

Objectives: An association has been suggested between trauma and neurological degenerative diseases. Magnetic resonance imaging has revealed that traumatic brain injury (TBI) can cause primary lesions in the midbrain including the substantia nigra (SN). Dopamine transporter (DAT) is mainly expressed in the SN, ventral tegmental area (VTA), and retrorubral field (RRF) of the ventral midbrain. Previous western blot studies have examined DAT levels in the rat frontal cortex and striatum after a controlled cortical impact (CCI); however, no study has comprehensively examined DAT expression in the midbrain following TBI in an animal model.

Methods: We used immunohistochemistry and in situ hybridization to examine the time-dependent changes in the expression of DAT in the midbrain during the first 14 days after TBI in a mouse CCI model.

Results: The expression of DAT protein in the RRF on the side ipsilateral to the site of injury decreased in 14 days after injury. Dopamine transporter mRNA expression in the RRF on the ipsilateral side decreased in 1, 7, and 14 days and increased in 4 days after injury.

Discussion: These findings indicated that TBI induced changes in DAT expression in the RRF. Because the DAT pumps dopamine (DA) out of the synapse back into the cytosol and maintains DA homeostasis, the decreased expression of DAT after TBI may result in decreased DA neurotransmission in the brain.

Keywords:

• Head trauma
• Dopamine transporter
• Retrorubral field
• In situ hybridization