Upon activation, brain macrophages, the microglia, release proinflammatory mediators that play important roles in eliciting neuroinflammatory responses associated with neurodegenerative diseases. As resveratrol, an antioxidant component of grape, has been reported to exert anti-inflammatory activities on macrophages, we investigated its effects on the production of TNF-alpha (TNF-α) and nitric oxide (NO) by lipopolysaccharide (LPS)-activated microglia. Exposure of cultured rat cortical microglia and a mouse microglial cell line N9 to LPS increased their release of TNF-α and NO, which was significantly inhibited by resveratrol. Further studies revealed that resveratrol suppressed LPS-induced degradation of IκBα, expression of iNOS and phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in N9 microglial cells. These results demonstrate a potent suppressive effect of resveratrol on proinflammatory responses of microglia, suggesting a therapeutic potential for this compound in neurodegenerative diseases accompanied by microglial activation.

It is controversial regarding to the roles of acetaldehyde and ethanol in the central nervous system. In the present study, the effects of acetaldehyde and ethanol on extracellular levels of glutamate, taurine and GABA in the anterior cingulate cortex (ACC) of freely moving rats were investigated by using the microdialysis technique coupled to high performance liquid chromatography (HPLC) with fluorescent detection. The result showed that glutamate levels were significantly decreased after acute administration of acetaldehyde (AcH, 20 and 100mg/kg, i.p.), while taurine levels were significantly increased after the higher dose of acetaldehyde (100mg/kg, i.p.). GABA levels had no changes at any doses of acetaldehyde tested. Interestingly, similar changes of these amino acids were induced by ethanol (EtOH, 3g/kg, i.p.) when sodium azide (NaN3, 10mg/kg, i.p.), a catalase inhibitor that can reduce brain ethanol metabolism, was used simultaneously. These findings suggest that acetaldehyde and ethanol have the similar effects on the extracellular output of glutamate, taurine and GABA in the ACC.

The mechanism of ethanol, morphine, methamphetamine (MAP), and nicotine-induced ascorbic acid (AA) release in striatum, and nucleus accumbens (NAc) is not well understood. Our previous study showed that the glutamatergic system was involved in the addictive drug-induced AA release in NAc and striatum. Furthermore, frontal decortication eliminates drug-induced ascorbic acid release in the striatum but not in the NAc. In the present study, the roles of the hippocampus in drug-induced AA release in the striatum and NAc were studied by using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). Ethanol (3.0 g/kg, i.p.), methamphetamine (3.0 mg/kg, i.p.), and nicotine (1.5 mg/kg, i.p.) significantly stimulated AA release in the striatum and NAc, respectively. Morphine (20 mg/kg, i.p.) significantly stimulated AA release in the striatum, but not in the NAc. After hippocampal lesion by kainic acid, AA release induced by ethanol, methamphetamine, and nicotine could be eliminated in NAc, but not in the striatum. These results suggest that the hippocampus might be a common and necessary area in addictive drug-induced AA release in the NAc, which also imply that different pathways might be involved in drug-induced AA release in the striatum and the NAc of the rats.

Schizophrenia is a devastating illness of unknown etiology and the basis for its treatment rests in the symptomatic response to antipsychotics. It was found that some of the patients with schizophrenia elicited microglia activation. The present study used lipopolysaccharide (LPS)-activated mouse microglial cell line N9 as an in vitro model to mimic microglia activation seen in the patients with schizophrenia. The effects of clozapine, olanzapine and haloperidol on the release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The results showed that olanzapine significantly inhibited NO release by LPS-stimulated N9 cells. Clozapine and haloperidol did not show significant effects on this model. The present study suggested that the inhibiting effect of olanzapine on the NO release by LPS-stimulated microglial cells might be a new mechanism through which olanzapine exhibits its therapeutic effect in the treatment of schizophrenia.

Many schizophrenic patients exhibit impairments in neurocognitive functions. Typical antipsychotic drugs such as haloperidol, have limited or even detrimental influence on cognitive functions. In contrast, atypical antipsychotic drugs, such as clozapine and olanzapine, may improve memory function in schizophrenics. However, only a few studies have been conducted to directly compare the effects of olanzapine, clozapine and haloperidol on memory functions in animal models. Thus, their effects on this issue were investigated in the present studies by using one-way step-through passive avoidance task and Morris water maze as models of learning and memory. The results showed that olanzapine did not affect acquisition, consolidation or retrieval process in step-through test. Moreover, it improved spatial learning function in mice in Morris water maze task. Clozapine and haloperidol appeared to impair acquisition process and consolidation process, respectively, in step-through test. Both drugs impaired spatial learning function in mice in Morris water maze task. The results suggested a positive implication for the clinical medication of olanzapine in schizophrenic treatment.

The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17β-estradiol (E2, n=10, 2μg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs. OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

The effect of oleamide on apoptosis was investigated by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction assay, DNA staining assay with propidiumiodide and caspase-3 activity analyses. The present results showed that oleamide significantly attenuated the cell death and nuclear condensation of cultured rat cerebellar granule neurons induced by K+ deprivation in a dose-dependent manner. The oleamide actions were well parallel with the attenuation of caspase-3 activity in the process of apoptotic death. Moreover, neither elaidic acid nor stearic acid, two fatty acids structurally related to oleamide without the Δ9-cis double bond, had similar effects on the cell death, suggesting the selectively structural features of oleamide required for this action. These data provided the first evidence of a protective effect of oleamide against apoptosis in a structurally specific manner.

Opiate abuse is associated with long-lasting neural adaptative changes in the brain. Increasing evidence demonstrates that opiates significantly alter the function of the glutamatergic system, while how the system is regulated still remains elusive. In the present study, we studied the effect of morphine on extracellular glutamate concentration in the hippocampus, a nucleus rich of the glutamatergic neurons. The results showed that glutamate concentration in the extracellular fluid of the hippocampus was decreased following either acute or chronic treatment of morphine. However, naloxone-induced withdrawal increased glutamate concentration significantly. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine treatment.

Previous studies have shown that striatumand nucleus accumbens (NAc) are two different structures inmediating addictive drug-induced ascorbic acid (AA) release. In order to further characterize the different effects of drugs-induced AA release in the striatum and NAc, in the present study, we investigated the effect of ethanol, morphine, methamphetamine, nicotine-induced AA release in these two nuclei using microdialysis coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD). All drugs were continuously perfused directly into the striatum or NAc. This study showed that local intrastriatal or intra-accumbensal perfusion of ethanol (500 μM) could increase AA release to 280, 260% in the striatum and NAc, respectively. Intra-striatal infusion of morphine (1mM), methamphetamine (250 μM) or nicotine (500 μM), reduce striatal AA release to 48, 50, 45%, respectively. While given intra-accumbensally, morphine (1mM), methamphetamine (250 μM) or nicotine (500 μM) increase AA release to 165, 160, 160%, respectively. These results suggested that different presynaptic or postsynaptic mechanisms might be involved in addictive drug-induced AA release in the striatum and NAc.

In the present study, pseudoginsenoside-F11 (PF11), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10mg/kg four times at 2-h intervals, and PF11 was orally administered at the doses of 4 and 8mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF11 did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF11 significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF11 greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF11 significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3, 4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5- hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF11 could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF11 is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.