Inhibition of tubulin detyrosination:a novel strategy to promote central nervous system regeneration

The adult mammalian central nervous system(CNS) coordinates essential functions such as sensation,movement,autonomic control,thought processes,and communication.Consequently,injuries or diseases of the CNS are often associated with devastating and permanent functional impairments because damaged axons normally fail to regenerate.An insufficient neuron-intrinsic growth capacity and an inhibitory environment at the injury site are the leading causes of this regenerative failure.

Mapping of liver-enriched transcription factors in the human intestine

AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.

Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress

Shen Yuan Gan（SYG） is a Chinese herbal prescription composed of total saponins of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia（2：1）.Our previous studies have demonstrated that SYG has antidepressant-like effects in various mouse models of behavioral depression.The present study aimed to test whether SYG affected chronic mild stress（CMS）-induced depression and cognitive impairment in mice.We found that a 5-week CMS schedule induced significant degradation of the coat state,decreased sucrose intake in the sucrose-preference test,and increased the latency to feed in the noveltysuppressed feeding test.All of these CMS-induced changes were ameliorated by SYG（100 and 200 mg/kg） and fluoxetine（10 mg/kg）.In addition,SYG restored the decreased monoamine neurotransmitter concentrations（serotonin,dopamine,norepinephrine and acetylcholine） induced by CMS in the prefrontal cortex.Interestingly,SYG ameliorated CMS-induced cognitive impairment in the step-through test,and increased the acetylcholine level in the prefrontal cortex.These results suggest that SYG has an antidepressant-like action and enhances cognition by modulating the serotonin,dopamine,norepinephrine,and acetylcholine levels in the prefrontal cortex.

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

Objectives： The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polyga- lasaponin （HPS） on senescence accelerate mouse P8 （SAMP8） mice, an effective Alzheimer＇s disease （AD） model, and to research the relevant mechanisms. Methods： The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze （MWM） and step-through passive avoidance tests. Then N-methyl-D-aspartate （NMDA） receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blot- ting. Results： HPS （25 and 50 mg/kg） improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice. Conclusions： The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor （NMDAR）-related pathways.