title: 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.
authors.affiliation: Vivian L. Smith Center for Neurological Research, Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, 77225, USA.
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Kobori
authors.forename: Guy L
authors.initials: GL
authors.lastname: Clifton
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Dash
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000096:biosynthesis*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002395:Catecholamines