The research objective of my laboratory is to explore the molecular mechanisms contributing to working memory (lasting seconds), short-term memory (lasting minutes-to-hours) and long-term memory (lasting days to a lifetime), and the relationships between these types of memories. To accomplish this, we disrupt or augment specific biochemical events in discrete brain regions such as the prefrontal cortex and the hippocampus, to determine the aspect of memory altered as a result of the manipulation. Human and animal studies have shown that the prefrontal cortex is required for holding information “online” for a period of seconds (referred to as working memory) which is used to guide goal-directed behavior. Working memory is critical for decision making and coherent thought processes, and is often impaired as a result of normal aging, and diseases such as Parkinson’s, Alzheimer’s and schizophrenia. Short-and long-term explicit memories are dependent on the function the hippocampus, a structure within the medial temporal lobe. We utilize a multi-disciplinary approach involving molecular, biochemical, genetic and behavioral techniques to manipulate molecular processes within the prefrontal cortex and hippocampus to determine their contribution to various memory processes.
Both the prefrontal cortex and hippocampus are highly vulnerable to insults such as traumatic brain injury. Injury to these structures often results in memory loss and a lack of coherent thought processes. Biochemical and molecular cascades initiated as a result of trauma are thought to alter inter- and intracellular signaling, causing changes in the brain ranging from survival and growth to neuronal dysfunction and death. We use an experimental brain injury model in rodents to explore some of the molecular mechanisms contributing to injury-related memory deficits. The long-term goal of this research is to identify potential targets for therapeutic interventions to alleviate the memory disorders associated with brain injuries and degenerative diseases.
Dash, PK, Kobori, N, Moore, AN. A molecular description of brain trauma pathophysiology using microarray technology: an overview. 2004 Neurochem. Res. 29:1275-1286.
Dash, PK, Mach, SA, Moody, MR, Moore, AN. Performance in long-term memory tasks is augmented by a phosphorylated growth factor receptor fragment. 2004 J. Neuroscience Research 15:205-216.
Dash PK, Hebert AE, Runyan JM. A unified theory for cellular and systems memory consolidation. Brain Res. Review 45:30-37.
Runyan JD, Moore AN, Dash PK. A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory. Learn Mem. 2005 Mar-Apr
Jeter CB, Hergenroeder GW, Ward Iii NH, Moore AN, Dash PK. Human traumatic brain injury alters circulating L-arginine and its metabolite levels: possible link to cerebral blood flow, extracellular matrix remodeling, and energy status. 2011 J Neurotrauma. Sep 26
Dash PK, Johnson D, Clark J, Orsi SA, Zhang M, Zhao J, Grill RJ, Moore AN, Pati S. Involvement of the Glycogen Synthase Kinase-3 Signaling Pathway in TBI Pathology and Neurocognitive Outcome. 2011 PLoS One. Sept 15
Zhao J, Redell JB, Moore AN, Dash PK. A novel strategy to activate cytoprotective genes in the injured brain. 2011 Biochem Biophys Res Commun. Mar 22.
Redell JB, Zhao J, Dash PK. Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury. 2010 J Neurosci Res Dec 8.
Redell JB, Moore AN, Ward NH 3rd, Hergenroeder GW, Dash PK. Human traumatic brain injury alters plasma microRNA levels. 2010 J Neurotrauma. Nov 23.
Dash PK, Orsi SA, Zhang M, Grill RJ, Pati S, Zhao J, Moore AN. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. 2010 PLoS One Jun 30
Hill J, Zhao J, Dash PK. High blood glucose does not adversely affect outcome in moderately brain-injured rodents. 2010 J Neurotrauma Aug 27
Hergenroeder GW, Moore AN, McCoy JP Jr, Samsel L, Ward NH 3rd, Clifton GL, Dash PK. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury. 2010 J Neuroinflammation March 11
Dash PK, Zhao J, Hergenroeder G, Moore AN. Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. 2010 Neurotherapeutics Jan;7
Dash PK, Orsi SA, Moore AN. Histone deactylase inhibition combined with behavioral therapy enhances learning and memory following traumatic brain injury. 2009 Neuroscience June 13
Dash PK, Zhao J, Orsi SA, Zhang M, Moore AN. Sulforaphane improves cognitive function administered following traumatic brain injury. 2009 Neuroscience Letters Aug 28
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