Prodynorphin mRNA expression in the rat dentate gyrus after cerebral ischemia.
ABSTRACT The beneficial effects of exogenous kappa receptor agonists in preventing neuronal damage elicited by brain ischemia suggest a role for endogenous dynorphins. In agreement prodynorphin (PDYN) gene expression in granule cells of the dentate gyrus detected by in situ hybridization was drastically but transiently decreased 18-32 h after four-vessel cerebral ischemia for 20 min in rats. We propose that decreased dynorphin synthesis and release could contribute to the delayed neuronal death of hippocampal pyramidal cells in this model.
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ABSTRACT: The purpose of this study was to evaluate behavioural effects of an extremely low frequency magnetic field (ELF-MF) in 3-month-old Mongolian gerbils submitted to global cerebral ischemia. After 10-min occlusion of both common carotid arteries, the gerbils were placed in the vicinity of an electromagnet and continuously exposed to ELF-MF (50Hz, 0.5mT) for 7 days. Their behaviour (locomotion, stereotypy, rotations, and immobility) was monitored on days 1, 2, 4, 7, and 14 after reperfusion for 60min in the open field. It was shown that the 10-min global cerebral ischemia per se induced a significant motor activity increase (locomotion, stereotypy and rotations), and consequently immobility decrease until day 4 after reperfusion, compared to control gerbils. Exposure to ELF-MF inhibited development of ischemia-induced motor hyperactivity during the whole period of registration, but significantly in the first 2 days after reperfusion, when the postischemic hyperactivity was most evident. Motor activity of these gerbils was still significantly increased compared to control ones, but only on day 1 after reperfusion. Our results revealed that the applied ELF-MF (50Hz, 0.5mT) decreased motor hyperactivity induced by the 10-min global cerebral ischemia, via modulation of the processes that underlie this behavioural response.Behavioural brain research 11/2011; 228(2):241-6. DOI:10.1016/j.bbr.2011.10.046 · 3.39 Impact Factor
Article: Endogenous opiates: 1996.[Show abstract] [Hide abstract]
ABSTRACT: This paper is the nineteenth installment of our annual review of research concerning the opiate system. It summarizes papers published during 1996 reporting the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress, tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunological responses; and other behaviors.Peptides 02/1997; 18(10):1651-88. DOI:10.1016/S0196-9781(97)00264-7 · 2.61 Impact Factor
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ABSTRACT: Dynorphins, endogenous peptide neurotransmitters expressed in the central nervous system, have been implicated in diverse pathophysiological processes, including excitotoxicity, chronic inflammation, traumatic injury, cognitive impairment, and motor dysfunction, with significant changes with aging or age-related disease processes. This has led to the hypothesis that the suppression of dynorphin expression would produce beneficial effects on learning and memory and motor function. To assess the phenotypic manifestations of chronic suppression of endogenous dynorphin, knockout (KO) mice lacking the coding exons of the gene encoding the prodynorphin (Pdyn) precursor protein, were tested in a series of behavioral, biochemical, and molecular biological studies. Moderately aged Pdyn KO perform comparatively better than similarly aged wild-type (WT) mice in the water maze task, although no Pdyn effect was seen among young adult mice. In addition, young adult Pdyn KO mice show mildly improved performance on a passive avoidance task. Minimal baseline differences were noted in spontaneous locomotor activity in an open-field assay, but Pdyn deletion produced a relative sparing of motor dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To investigate the relationship between aging and brain dynorphin expression in mice, we examined dynorphin peptide levels at varying ages in hippocampus, striatum, and frontal cortex of WT mice by quantitative radioimmunoassay. While aging produces progressive decline in Dyn B in striatum and frontal cortex, Dyn A shows an upward trend in frontal cortex without significant change in striatum. Systemic MPTP produces significant short-term elevations in dynorphin peptides that regress to below baseline by 7 days. HPLC analysis of striatal dopamine shows an age-dependent increase in basal dopamine levels in Pdyn KO mice, an effect that is abolished after MPTP. Western blotting experiments demonstrate that Pdyn deletion is associated with greater phosphorylation at the serine-40 site of tyrosine hydroxylase (TH) despite relatively less total TH immunoreactivity, suggesting a suppressive effect of dynorphins on dopamine synthesis. Microarray analysis of hippocampal tissue from young and aged WT and Pdyn KO mice reveals a number of functional groups of genes demonstrating altered expression. The results of this dissertation support a role of endogenous dynorphins in age-associated cognitive and motor dysfunction.