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Selected AbstractsKey role for enkephalinergic tone in cortico,striatal,thalamic functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Marylou V. Solbrig Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions. We also find increased preproenkephalin in infected cultured neuroblastoma and rat foetal glial cells. The expression pattern of enkephalin mRNA in vivo and in vitro suggest that increased enkephalin function is one of the neuropharmacological means by which Borna disease virus causes motor disease of animals and possibly cognitive and affective disease in man, and further suggest that enkephalins play a critical role in the maintenance of a balanced tone of activity in the cortico-basal ganglia-thalamo-cortical loops. [source] Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference,HEPATOLOGY, Issue 6 2007Shirish Paranjpe Hepatocyte growth factor (HGF) and its receptor c-Met are involved in liver regeneration. The role of HGF and c-Met in liver regeneration in rat following two-thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c-Met in separate experiments. A mixture of 2 c-Met-specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF-specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine. Rats were injected with the ShRNA/PEI complex 24 hours before and at the time of PHx. A mismatch and a scrambled ShRNA served as negative controls. ShRNA treatment resulted in suppression of c-Met and HGF mRNA and protein compared with that in controls. The regenerative response was assessed by PCNA, mitotic index, and BrdU labeling. Treatment with the ShHGF mixture resulted in moderate suppression of hepatocyte proliferation. Immunohistochemical analysis revealed severe suppression of incorporation of BrdU and complete absence of mitosis in rats treated with ShMet 24 hours after PHx compared with that in controls. Gene array analyses indicated abnormal expression patterns in many cell-cycle- and apoptosis-related genes. The active form of caspase 3 was seen to increase in ShMet-treated rats. The TUNEL assay indicated a slight increase in apoptosis in ShMet-treated rats compared with that in controls. Conclusion: The data indicated that in vivo silencing of c-Met and HGF mRNA by RNA interference in normal rats results in suppression of mRNA and protein, which had a measurable effect on proliferation kinetics associated with liver regeneration. (HEPATOLOGY 2007.) [source] Effect of some medicinal plants on plasma antioxidant system and lipid levels in ratsPHYTOTHERAPY RESEARCH, Issue 5 2005Eun-Mi Choi Abstract Several inflammatory diseases are thought to be related to oxidative injury and free oxygen radicals have been proposed as important causative agents of heart disease and aging. To investigate the effects of daily intake of medicinal plants on antioxidant enzymes, lipid peroxidation and lipid profiles in rat, 28 rats were randomly divided into four groups and administered with three plant extracts (0.2 g/kg body weight): Piper cubeba (fruit), Physalis angulata (flower), Rosa hybrida (flower) and with saline as a control. After 3 weeks, superoxide dismutase (SOD), catalase, thiobarbituric acid reactive substance (TBARS), triglyceride (TG) and cholesterol levels in plasma were measured. The SOD activity of the Piper cubeba group and the catalase activity of the Piper cubeba and Rosa hybrida groups were significantly increased compared with the control group, while the SOD and catalase activities of the Physalis angulata group were not significantly changed (p < 0.05). TBARS, a marker of lipid peroxidation, was significantly lower in all experimental groups compeered with the control group. No significant changes occurred in the TG, total- and LDL-cholesterol of all groups, but the HDL-cholesterol of the Physalis angulata group was significantly increased. This study showed that the intake of medicinal plants in rats results in an increase in antioxidant enzyme activity and HDL-cholesterol, and a decrease in malondialdehyde, which may reduce the risk of inflammatory and heart disease. Copyright © 2005 John Wiley & Sons, Ltd. [source] Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensationTHE JOURNAL OF PHYSIOLOGY, Issue 3 2006Adrian Miranda The role of intramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague,Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10,80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13,L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions , 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 ± 2.2 impulses s,1), but not SL-A neurons (5.3 ± 0.9 impulses s,1) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 ± 0.8 impulses s,1; SL-A, 3.1 ± 0.7 impulses s,1). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures , 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation. [source] Effects of nicotine and chlorisondamine on cerebral glucose utilization in immobilized and freely-moving ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2000T Marenco Chlorisondamine blocks central nicotinic receptors for many weeks via an unknown mechanism. Intracerebroventricular administration of [3H]-chlorisondamine in rats results in an anatomically restricted and persistent intracellular accumulation of radioactivity. The initial aim of the present study was to test whether nicotinic receptor antagonism by chlorisondamine is also anatomically restricted. Male adult rats were pretreated several times with nicotine to avoid the disruptive effects of the drug seen in drug-naïve animals. They then received chlorisondamine (10 ,g i.c.v.) or saline, and local cerebral glucose utilization (LCGU) was measured 4 weeks later after acute nicotine (0.4 mg kg,1 s.c.) or saline administration. During testing, rats were partially immobilized. Nicotine significantly increased LCGU in the anteroventral thalamus and in superior colliculus. Chlorisondamine completely blocked the first of these effects. Chlorisondamine significantly reduced LCGU in the lateral habenula, substantia nigra pars compacta, ventral tegmental area, and cerebellar granular layer. The second experiment was of similar design, but the rats were not pre-exposed to nicotine, and were tested whilst freely-moving. Acute nicotine significantly increased LCGU in anteroventral thalamus, superior colliculus, medial habenula and dorsal lateral geniculate. Overall, however, nicotine significantly decreased LCGU. Most or all of the central effects of nicotine on LCGU were reversed by chlorisondamine given 4 weeks beforehand. These findings suggest that chlorisondamine blocks nicotinic effects widely within the brain. They also indicate that in freely-moving rats, nicotine can reduce or stimulate cerebral glucose utilization, depending on the brain area. British Journal of Pharmacology (2000) 129, 147,155; doi:10.1038/sj.bjp.0703005 [source] |