Expression of the prodynorphin gene after experimental brain injury and its role in behavioral dysfunction.
Traumatic brain injury (TBI) causes excess release of neurotransmitters, such as glutamate, and increases intracellular calcium levels. Elevated levels of calcium, and perhaps other intracellular second messengers, as a result of TBI can alter the expression of many genes. The protein products of some of these genes may be signals for TBI-associated memory dysfunction. Therefore, identification of genes whose expression is altered after TBI in the hippocampus, a structure in the medial temporal lobe that plays a critical role in memory formation and storage, and elucidation of the role(s) of their protein products may shed light on the molecular mechanisms underlying TBI-elicited memory dysfunction. The prodynorphin gene is expressed in hippocampal granule cells, and its expression has been reported to be enhanced as a result of elevated intracellular calcium. The prodynorphin protein is proteolytically cleaved to generate multiple dynorphin peptides, which can modulate neurotransmitter release through the activation of presynaptic kappa opioid receptors. In this study, we report that 1) TBI transiently increases prodynorphin mRNA in the hippocampus, 2) dynorphin peptide immunoreactivity is enhanced for up to 24 hr after TBI and 3) intracerebroventricular infusion of the kappa receptor antagonist nor-binaltorphimine (nor-BNI) impairs subsequent performance in a spatial memory task. These results suggest that dynorphin action may serve a beneficial role after TBI.
Redell
John B
JB
The Vivian L Smith Center for Neurologic Research, Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77225, USA.
Moore
Anthony N
AN
Dash
Pramod K
PK
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001930:Brain Injuries / Q000235:genetics*; D017931:DNA Primers; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors
D017931:DNA Primers; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; C033660:preproenkephalin