Enhanced Catecholamine Synthesis in the Prefrontal Cortex after Traumatic Brain Injury: Implications for Prefrontal Dysfunction
Abstract
Traumatic brain injury (TBI)--induced dysfunction of the prefrontal cortex causes many high-level cognitive deficits, including working memory (WM) dysfunction. WM lies at the core of many high-level functions, yet the cellular and molecular mechanisms underlying its dysfunction are poorly understood. Lesion and pharmacological studies in rodents have implicated the medial prefrontal cortex (mPFC), which includes the prelimbic/infralimbic (PL/IL) cortices, in WM tasks. These studies have shown that optimal levels of catecholamine neurotransmission are critical for normalcy of WM function, suggesting that alterations in their synthesis may play a role in WM dysfunction. Using the cortical impact injury model of traumatic brain injury which reproducibly causes working memory deficits in rodents, we have measured the protein levels and activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine biosynthesis, and tissue dopamine (DA) and norepinephrine (NE) levels in microdissected PL/IL tissues. Our results show that TBI increases TH protein levels, its activity and tissue DA and NE content in the PL/IL. These findings suggest that altered catecholamine signaling within the PL/IL may contribute to impaired PFC function, and may have implications in the design and implementation of strategies to alleviate prefrontal dysfunction in brain injury patients.
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Traumatic brain injury (TBI) induces elevated catecholamine signaling in the PFC.
“Similarly, traumatic brain injury (TBI) induces elevated catecholamine signaling in the PFC107 and elevated α1-AR expression that contributes to working memory impairment108.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [107]
Cites
A controlled cortical impact model of traumatic brain injury in the rat
Edward Dixon, C., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., & Hayes, R. L. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90104-8 · Cited by 1,141 · see citing works
Self-citationTyrosine hydroxylase phosphorylation: Regulation and consequences
Dunkley, P. R., Bobrovskaya, L., Graham, M. E., Von Nagy‐Felsobuki, E. I., & Dickson, P. W. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02797.x · Cited by 455 · cited 2× · see citing works
“These increases in Ser31 and Ser40 phosphorylation are accompanied by enhanced TH activity (Dunkley et al., 2004).”
Circulating Catecholamines and Sympathetic Activity after Head Injury
Clifton, G. L., Ziegler, M. G., & Grossman, R. G. (1981) · Neurosurgery · doi:10.1227/00006123-198101000-00003 · Cited by 296 · cited 1× · see citing works
“Studies in humans have shown that circulating norepinephrine levels correspond to the level of injury with comatose patients having serum norepinephrine levels as high as seven times normal (Clifton et al., 1981).”
Self-citationRegulation of tyrosine hydroxylase by stress-activated protein kinases
Toska, K., Kleppe, R., Armstrong, C. G., Morrice, N. A., Cohen, P., & Haavik, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01172.x · Cited by 95 · cited 1× · see citing works
“Binding of 14-3-3 to TH enhances TH activity and dopamine synthesis (Toska et al., 2002; Yamauchi and Fujisawa, 1981).”
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Stress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Arnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
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Self-citationNoradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex
Datta, D., Yang, S.-T., Galvin, V. C., Solder, J., Luo, F., Morozov, Y. M., Arellano, J., Duque, A., Rakic, P., Arnsten, A. F. T., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2472-18.2019 · Cited by 44 · see citing works
- Authors
- Kobori, N., Clifton, G. L., & Dash, P. K.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2006-07
- Volume
- 23
- Issue
- 7
- Pages
- 1094-1102
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W2062419575
- Cited by
- 80
- References
- 4
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 35457, NS 049160, NS0523, R01NS049160, R01NS035457)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- traumatic brain injury, prefrontal cortex, catecholamine synthesis, tyrosine hydroxylase, dopamine, norepinephrine, working memory deficits, medial prefrontal cortex, prefrontal cortex dysfunction
- MeSH terms
- Animals, Brain Injuries, Catecholamines, Male, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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