Stretch-Induced Deformation as a Model to Study Dopaminergic Dysfunction in Traumatic Brain Injury

Hector Rosas-Hernandez, Susan M. Burks, Elvis Cuevas, Syed F. Ali

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Traumatic brain injury (TBI) is defined as damage to the brain that consequently disrupts normal function. Neuronal death, a hallmark of TBI, has been related to the development of neurodegenerative disorders like Parkinson’s disease (PD), where loss of dopaminergic neurons and dopaminergic dysfunction are observed. To date, no in vitro model exists in which the dopaminergic damage observed in TBI is replicated. In this study, we evaluated the effects of in vitro simulated TBI on human dopaminergic neurons. To simulate TBI, neurons were subjected to 0%, 5%, 10%, 15%, 25% and 50% deformation. 24 h after injury, cell viability and apoptosis were determined by lactate dehydrogenase (LDH) release and DNA fragmentation, as well as ethidium homodimer and caspase 3/7 staining. Dopamine (DA) levels were determined by ELISA. Levels of tyrosine hydroxylase (TH) and DA transporter (DAT) were determined by western blot. Only 50% stretch increased LDH release and ethidium homodimer staining, suggesting the induction of necrosis. On the contrary, 25% and 50% stretch increased DNA fragmentation while 15%, 25% and 50% increased caspase 3/7 staining, suggesting that moderate and severe TBI promote apoptosis. Levels of intracellular DA decreased in a stretch-dependent manner with 15%, 25% and 50% stretch, which were related with a decrease in TH expression. Extracellular DA levels increased only at 50%. Levels of DAT remained unchanged regardless of treatment. These data support the use of stretch as a model to simulate TBI in vitro in human dopaminergic neurons, replicating the acute effects of TBI in the dopaminergic system.

Original languageEnglish (US)
Pages (from-to)2546-2555
Number of pages10
JournalNeurochemical Research
Volume44
Issue number11
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Keywords

  • Apoptosis
  • Dopamine
  • In vitro models
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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