Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Analysis on Interrelation between Electroacupuncture-lnduced Cumulative Analgesic Effect and Hypothalamic Cholinergic Activities in Chronic Neuropathic Pain Rats

Objective： To observe the effects of repeated electroacupuncture （EA） of Zusanli （ST36）Yanglingquan （GB34） on hypothalamic acetylcholinesterase （AchE） and vesicular acetylcholine （ACh） transporter （VAChT） activities and choline acetyltransferase （CHAT） mRNA and muscarinic M1 receptor （MIR） mRNA expression in chronic constrictive injury （CCI） and/or ovariectomy （OVX） rats so as to reveal its underlying mechanism in cumulative analgesia. Methods： A total of 103 female Wistar rats were randomly divided into normal control （n=15）, CCI （n=15）, CCI＋EA2d （n=15）, CCI＋EA2W （n=15）, OVX＋CCI （n=13）, OVX＋CCI＋EA2d （n=15）, and OVX＋CCI＋EA2W groups （n=15）. CCI model was established by ligature of the unilateral sciatic nerve with surgical suture. Memory impairment model was established by removal of the bilateral ovaries. Morris water test was conducted to evaluate the OVX rats＇ memorylearning ability, and the thermal pain threshold （PT） of the bilateral paws was detected the next morning after EA. EA （2/15 Hz, 1 mA） was applied to bilateral ST36-GB34 for 30 min, once daily for 2 days or 2 weeks, respectively. Hypothalamic AChE activity was detected by histochemistry, VAChT immunoactivity was determined by immunohistochemistry, and ChAT mRNA and MIR mRNA expressions were assayed by reverse transcription-polymerase chain reaction （RT-PCR）. Results： In comparison with the normal control group, the AChE activity in hypothalamic arcuate nucleus （ARC） and supraoptic nucleus （SON） regions of CCI group, AChE activity in paraventricular nucleus （PVN）, ARC, and SON regions of OVX＋CCI group, and hypothalamic muscarinic M1R mRNA expression levels in both CCI and OVX＋CCI groups were down-regulated significantly （P〈0.05）. Compared with the CCI group, the AChE activities in hypothalamic ARC and SON regions of CCI＋EA2d and CCI＋EA2W groups and PVN region of CCI＋EA2W group and hypothalamic ChAT mRNA and M1R mRNA expression levels in CCi＋EA2W group were up-regulated considerably （P〈0.05）. In comparison with the OVX＋CCI group, the AChE activities in PVN, ARC, and SON regions and the expressions of hypothalamic ChAT mRNA and VAChT in ARC region of OVX＋CCI＋EA2W group were up-regulated remarkably （P〈0.05）. The effects in rats of CCI＋EA2W group were evidently superior to those of OVX＋CCI＋EA2d group in up-regulating AChE activities in PVN, ARC, and SON regions, VAChT immunoactivity in ARC region, and expression levels of hypothalamic ChAT mRNA and MIR mRNA （P〈0.05）. Similar situations were found in OVX＋CCI rats after EA2W. It suggested a cumulative effect after repeated EA of ST36-GB34. Comparison between CCI＋EA2W and OVX＋CCI＋EA2W groups showed that the effects in rats of the former group were evidently better than those of the latter group in up-regulating AChE activity in ARC and SON regions and the expressions of hypothalamic ChAT mRNA and M1 mRNA （P〈0.05）, suggesting a reduction of EA2W effects after OVX. Conclusion： Repeated EA can significantlyup-regulate AChE and VAChT activities and ChAT mRNA and MIR mRNA expressions in the hypothalamus of CCI and OVX＋CCI rats, which may contribute to the cumulative analgesic effects of repeated EA and be closely related to the animals＇ neuromemory ability.

Purification and Characterization of a Novel Tetradecapeptide from Ginseng Polypeptides with Enhancing Memory Activity for Mice

Aiming at isolating and investigating the active ingredients of the aqueous extract from Panax ginseng which showed enhancing memory activity, the authors characterized one ingredient. To separate the oligosaecharides and polypeptides, a DEAE-Sephadex A-50 colum was used. The enhanced memory activity in mice was studied by Mirros water maze tesk in mice. The dose of oligosacchrides, polypeptides or Piracetam was 30 mg/kg per day with intraperitoneal administration. The oligosaccharides did not show enhancing memory effect, but polypeptides did show. This result demonstrates that the active ingredients of the aqueous extract from Panax ginseng which showed enhancing memory effect was polypeptides. The purification of the polypeptides was performed on a Sephadex G-25 column. A novel tetradeeapeptide was purified from the polypeptides and its structure was determined by liquid chromatography-eleetrospray ionization-quadrupole-time of flight-mass spectrometry（LC-ESI-Q-TOF-MS） with the amino acid sequence of Lys-Ser-Leu-Thr-Leu-Thr-Ser-Ser-Leu-Ser-Tyr-Thr-Asp-Ser.

Locomotor activity and anxiety status, but not spatial working memory,are affected in mice after brief exposure to cuprizone

Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behaviors.This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders.We used the cuprizonetreated mouse model to test both tissue changes and behavioral functions（locomotor activity,anxiety status,and spatial working memory）.The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein,while the number of mature oligodendrocytes was reduced.The number and length of Caspr protein clusters,a structural marker of the node of Ranvier,did not change.The locomotor activity of the cuprizonetreated mice increased whereas their anxiety levels were lower than in normal controls;spatial working memory,however,did not change.These results,for the first time,link emotion-related behavior with mild white matter damage in cuprizone-treated mice.

Weak magnetic field accelerates chromate removal by zero-valent iron

Weak magnetic field（WMF） was employed to improve the removal of Cr（VI） by zero-valent iron（ZVI） for the first time. The removal rate of Cr（VI） was elevated by a factor of 1.12-5.89 due to the application of a WMF, and the WMF-induced improvement was more remarkable at higher Cr（VI） concentration and higher p H. Fe2＋was not detected until Cr（VI） was exhausted, and there was a positive correlation between the WMF-induced promotion factor of Cr（VI） removal rate and that of Fe2＋release rate in the absence of Cr（VI） at pH 4.0-5.5. These phenomena imply that ZVI corrosion with Fe2＋release was the limiting step in the process of Cr（VI） removal. The superimposed WMF had negligible influence on the apparent activation energy of Cr（VI） removal by ZVI, indicating that WMF accelerated Cr（VI）removal by ZVI but did not change the mechanism. The passive layer formed with WMF was much more porous than without WMF, thereby facilitating mass transport. Therefore,WMF could accelerate ZVI corrosion and alleviate the detrimental effects of the passive layer, resulting in more rapid removal of Cr（VI） by ZVI. Exploiting the magnetic memory of ZVI, a two-stage process consisting of a small reactor with WMF for ZVI magnetization and a large reactor for removing contaminants by magnetized ZVI can be employed as a new method of ZVI-mediated remediation.