No abstract

Background and Purpose-Glial cell line-derived neurotrophic factor (GDNF) plays important roles in the survival and recovery of some mature neurons under pathological conditions. However, the effect of GDNF in ameliorating ischemic brain injury has not been well documented. Therefore, we investigated a possible effect of GDNF on the changes of infarct size, brain edema, DNA fragmentation, and immunoreactivities for caspases after permanent middle cerebral artery occlusion (MCAO) in rats. Methods-For the estimation of ischemic brain injury, we calculated the infarct size of MCA region and also measured the brain water content as edema formation at 24 hours after the MCAO. Terminal deoxynucleotidyl transferasemediated dUTP-biotin in situ nick labeling (TUNEL) staining was performed for the detection of DNA fragmentation.Immunoreactivities for caspase-1 (ICE), caspase-2 (Nedd-2), and caspase-3 (CPP32) were stained. Results-Both infarct size and brain edema after permanent MCAO were significantly reduced by topical application of GDNF (48% and 30% decreases, Pϭ0.01). TUNEL staining and immunoreactivities for caspases were markedly induced at 12 hours after permanent MCAO in the vehicle-treated animals. However, the spatial distribution of those immunohistochemically positive cells was dissociative in each caspase. Induction of TUNEL staining and immunoreactivities for caspases-1 and -3 was greatly reduced with GDNF treatment, whereas the reduction of caspase-2 staining was only minimum. Conclusions-These data suggest that the reduction of infarct size and brain edema by GDNF was greatly associated with the reduction of DNA fragmentation and apoptotic signals predominantly through caspases-1 and -3 cascades. (Stroke.

Experiments were conducted to measure the effect of feeding by the planthopper Nilaparvata lugens (Stål) on photosynthesis and the translocation of assimilates in rice plants, Oryza sativa L. We used mature japonica rice plants and applied the 13CO2 feeding method to evaluate those physiological effects. The photosynthetic rate was suppressed by N. lugens infestation, especially at the lower leaf position, with rates 30% lower than that of control plants at the booting stage. Leaf nitrogen concentration in infested plants was also lower than that in control plants. After flowering, the chlorophyll content and total plant dry weight were reduced by N. lugens. Stem and sheath dry weights were significantly reduced by N. lugens infestation, whereas panicle dry weight was not affected. Little effect was found on disruption in translocation of assimilates, even when 13CO2 was supplied to the infested leaves. Results suggested that removal of assimilates and reduction in photosynthesis by N. lugens have the greatest effect on growth and yield of rice plants as compared with the disruption in the translocation of assimilates. Plant death can occur by N. lugens infestation if the amount of energy supplied is less than that required for tissue maintenance.

The antipsychotic efficacy of aripiprazole is not generally associated with extrapyramidal symptoms, cardiovascular effects, sedation or elevations in serum prolactin that characterize typical or atypical antipsychotics. The aim of this study was to clarify the mechanism of action of aripiprazole that underlies its favourable clinical profiles. The preclinical efficacy and side-effect profiles of aripiprazole were evaluated using several pharmaco-behavioural test systems in mice and rats, both in vivo and ex vivo, and compared with those of other conventional and atypical antipsychotics. Each of the antipsychotics induced catalepsy and inhibited apomorphine-induced stereotypy. The catalepsy liability ratios for these drugs were 6.5 for aripiprazole, 4.7 for both olanzapine and risperidone. The ptosis liability ratios for aripiprazole, olanzapine and risperidone were 14, 7.2 and 3.3, respectively. Aripiprazole slightly increased DOPA accumulation in the forebrain of reserpinised mice, reduced 5-HTP accumulation at the highest dose and exhibited a weaker inhibition of 5-methoxy-N,N-dimethyl-tryptamine-induced head twitches. Aripiprazole did not inhibit physostigmine- or norepinephrine-induced lethality in rats. In conclusion, aripiprazole shows a favourable preclinical efficacy and side-effect profile compared to a typical antipsychotics. This profile may result from its high affinity partial agonist activity at D2 and 5-HT1A receptors and its antagonism of 5-HT2A receptors.