Positive Cells In Hippocampus Research Articles

ADSC-Exosomes Alleviate MTX-induced Rat Neuronal Damage by Activating Nrf2-ARE Pathway

The aim of this study was to analyze the efficacy and underlying mechanism of adipose-derived mesenchymal stem cell exosome (ADSC-exosomes)–mediated protection on methotrexate (MTX)–induced neuronal damage. We established a H2O2­induced oxidative stress model in vitro, as well as an MTX-induced neuronal damage rat model in vivo. We analyzed the effects of ADSC-exosomes on neuronal damage and Nrf2-ARE signaling pathway in rats and related mechanisms. The morphological and functional recovery of rat hippocampal neurons by ADSC-exosomes was examined by Nissl staining and modified neurological severity score (mNSS) score. The activation of Nrf2-ARE pathway effectively inhibited H2O2-induced oxidative stress. ADSC-exosomes treatment restored the activity of hippocampal neuronal cells, reduced ROS production, and inhibited hippocampal neuronal cells apoptosis. In in vivo experiments, ADSC­exosomes ameliorates MTX-induced hippocampal neuron damage by triggering Nrf2­ARE pathway, decreasing IL-6, IFN-, and TNF-a levels and TUNEL positive cells in hippocampus, and repairing hippocampal neuronal cell damage. ADSC­exosomes ameliorated MTX-induced neuronal damage and suppressed oxidative stress induced by neuronal damage through the activation of Nrf2-ARE signaling pathway.

Effect of Memantine Hydrochloride on Homocysteine Level and Cognitive Function in Diabetic Vascular Dementia Model Mice

Increased Hcy has a toxic effect on nerve cells and can cause hippocampal death and directly damage the body’s cognitive function and memory ability, leading to the occurrence of vascular dementia. Hcy predicts vascular disease and might be a basis for clinical judgment. This article provides a new basis for the prevention and treatment of this disease by exploring the mechanism of action of memantine hydrochloride in diabetic vascular dementia. After grouping, mice walked through the Morris water maze to record the escape latency, and measured the Hcy level of the mice by high performance liquid chromatography. Observing the volume of brain atrophy in mice. GFAPT, APP, and CHAT level in mouse hippocampus was assessed by IHC and CHAT mRNA was detected by RT-PCR. Escape latency, Hcy level (11.46 ±0.74) yiimmol/L, brain atrophy volume (25.21 ±1.21) mm3, number of APP positive cells (46.7003±3.2431), number of GFAP positive cells (21.4000 ± 1.8127) were all significantly lower than those of model group. The positive rate of CHAT and the amount of CHAT mRNA in the memantine hydrochloride group was significantly elevated (P < 0.05) with higher CHAT mRNA than model group and lower than blank group (P < 0.05). Memantine hydrochloride could reduce the level of Hcy in mice, improve the cognitive function of mice with diabetic vascular dementia by improving the number of GFAP and CHAT positive cells in hippocampus and cortex, and increasing the amount of CHAT mRNA in brain tissue.

Paraoxon-induced damage in rat hippocampus is associated with alterations in the expression of apoptosis-related proteins

To determine the possible role of apoptosis in the development of paraoxon-induced brain damage, we evaluated expression of apoptosis-related proteins, the extent of neuronal damage, and activation of astrocytes in rat hippocampus. Adult male Wistar rats were intraperitoneally injected with one of three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle). After 14 or 28 days, expression of apoptosis-related proteins, including B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3, as well as the number of neurons and glial fibrillary acidic protein (GFAP) positive cells in hippocampus were examined by western blot, cresyl blue staining, and immunohistochemistry, respectively. After 14 and 28 days, Bax and caspase-3 proteins were significantly increased in rats receiving 0.7 and 1 mg/kg of paraoxon. A significant decrease in Bcl-2 protein levels was also observed in 0.7 and 1 mg/kg groups after 14 days and in 1 mg/kg group after 28 days. Animals treated with 1 mg/kg of paraoxon showed a significant decrease in the number of neurons in the CA1 area. Also, those treated with 0.7 and 1 mg/kg of paraoxon showed an increase in the number of GFAP positive cells in both CA1 and CA3 areas as well as a significant decrease in survived neurons in the CA3 area. Our results indicated that neuronal damage induced by convulsive doses of paraoxon in rat hippocampus is mediated in part through apoptosis mechanism. Activation of astrocytes might lead to reduced extent of damage and damage and consequently increased neuronal survival.

Abstract TP446: Rosuvastatin Improves Cerebral Hemodynamics in Rats With Chronic Cerebral Hypoperfusion

Objective: Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders, hemodynamics and blood composition changes, which can lead to neurodegenerative injury and cognitive dysfunction. Therefore, it is important to take measures to prevent or reverse its development. Methods: Eighty Sprague-Dawley rats were randomly divided into five groups: Sham group, Vehicle groups (2-week group and 4-week group), Rosuvastatin-treated groups (2-week group and 4-week group). Both vehicle and treated group rats were treated with bilateral common carotid artery occlusion (BCCAO). Then rats in the treated group were intravenously injection with rosuvastatin (0.2 mg/kg/day) daily for 14 days beginning 24 hours after BCCAO. The vehicle groups were given the same amount of saline. The MRI ASL technique was used to scan cerebral blood flow (CBF) at pre-occlusion, BCCAO, 1, 2, 3, and 4 weeks after operation. Morris water maze test detected spatial memory abilities of the treated and vehicle rats after BCCAO. Immunofluorescence staining was used to detect the expression of CD34, GFAP, NeuN and Caspase-3 positive cells in hippocampus. Results: CBF decreased significantly after BCCAO in both rosuvastatin-treated and vehicle groups and then increased gradually. The CBF of the treated group was basically recovered to baseline levels at 1 or 2 weeks after BCCAO. But it took the vehicle group 4 weeks to restore to baseline. The vertebral artery (VA) diameter of the treated group was greater than that of the vehicle group (p<0.05), and the recovery of CBF and the dilation of VA were more evident during the administration period. Similarly, the escape latency of the treated group rats was also less than the vehicle group in Morris Water Maze test. In addition, the number of CD34 + and NeuN + cells in the hippocampus of the treated group was more than that in the vehicle group (p<0.01), while the number of GFAP + and Caspase-3 + cells was less than in the vehicle group (p<0.01). Conclusion: Rosuvastatin can accelerate the recovery of cerebral blood flow in CCH rats, which may be related to the dilation of VAs and angiogenesis; and its effects on reducing astrocyte activation and neuroprotection may help to ameliorate cognitive dysfunction in CCH rats.

Effects of moxibustion on the structure and function of blood brain barrier in Alzheimer's disease model rats

To investigate the effects of moxibustion on the structure and function of blood-brain barrier in Alzheimer's disease (AD) model rats. Forty-eight SD rats were randomly divided into 4 groups: normal control group, sham operation group, model group, moxibustion group. Model group and moxibustion group rats were injected with aggregated Aβ25-35 by bilateral hippocampus. In the rat model, the sham-operated group was injected with the same amount of normal saline in the bilateral hippocampus, and the normal group was not treated. After successful modeling, the moxibustion treatment was given at 2～3 cm above the Baihui, Shenshu and Yintang points of the moxibustion group rats, each time for 10 min, once a day, continuous treatment for 21 d. The Morris water maze test was used to evaluate the learning and memory ability of rats in each group. The Evans blue method was used to detect the permeability of blood-brain barrier. The ultrastructure of blood-brain barrier was observed under electron microscope. The matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) positive cells in hippocampus were detected by immunohistochemistry. Compared with the sham operation group, the escape latency was significantly increased (P＜0.01), and the space exploration time was decreased (P＜0.01), the learning and memory function in model group was impaired seriously, the Evans blue content in the brain was increased significantly (P＜0.01), the perivascular edema became larger, and the blood-brain barrier structure function was impaired. At the same time, the positive expressions of MMP-2 and MMP-9 in hippocampus were increased significantly (P＜0.01). Compared with model group, the learning and memory ability in moxibustion group rats was enhanced (P＜ 0.05), the content of Evans blue in the brain was decreased (P＜0.05), the degree of perivascular edema was reduced, and the damage of blood-brain barrier was improved. Positive expressions of MMP-2 and MMP-9 in hippocampus were decreased (P＜0.05 or P＜ 0.01). Moxibustion can decrease the expressions of MMP-2 and MMP-9, and reduce the damage of the structure and function of blood-brain barrier, thereby improving the learning and memory ability of AD model rats, and exerting therapeutic effects.

Systemic infection and microglia activation: a prospective postmortem study in sepsis patients

BackgroundSystemic infection is associated with long-term cognitive deficits and functional decline. In this study we hypothesized that severe systemic inflammation leads to a neuroinflammatory response that is characterized by microglial activation, and that these effects might be more pronounced in patients using medication with anticholinergic side-effects.MethodsBased on the results of a pilot study in 8 patients, we assessed the number of MHC-II and CD-68 positive cells by immunohistochemistry and compared the number of microglia in specific brain regions of 16 well-characterized patients with septic shock and 15 controls.ResultsIn the pilot study, patients with sepsis tended to have higher density of MHC-II and CD-68 positive microglia in the basal ganglia (putamen, caudate nucleus and globus pallidus) and of MHC-II positive microglia in the hippocampus. In the validation study, patients with sepsis had a significantly higher number of CD-68 positive cells in hippocampus (1.5 fold; p = 0.012), putamen (2.2 fold; p = 0.008) and cerebellum (2.5 fold; p = 0.011) than control patients. The density of MHC-II positive microglia was similar between sepsis and control groups. There was no consistent correlation between microglia counts and anti-cholinergic activity drugs score.ConclusionIn patients who die during septic shock, severe systemic inflammation is accompanied by localized and strong upregulation of CD-68 positive microglia, but not of MHC-II positive microglia. We identified regional differences in the brain with increased microglial activation in putamen, hippocampus and cerebellum.

Neurogenesis changes and the fate of progenitor cells after subarachnoid hemorrhage in rats

BackgroundSubarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease that leads to poor outcomes. Neurogenesis, an essential recovery mechanism after brain injury, has not been fully elucidated after SAH. MethodsA total of 122 SD rats were used in this study. For experiment one, the rats were randomly divided into six groups: sham and SAH with different time points (1,3,5,7,14 days) (n = 12/group). An endovascular perforation method was conducted for SAH model. Rats were injected with 5-Bromo-2′-deoxyuridine (BrdU, 50 mg/kg) 24 h before euthanasia at different time points after SAH. The BrdU labeled cells were detected by immunohistochemistry; Doublecortin (DCX) and glial fibrillary acidic protein (GFAP) were measured by western blot and immunohistochemistry. For experiment two, rats were randomly divided into five groups: sham and SAH with different time points (1, 2, 4, 8 weeks) (n = 6/group). Rats received BrdU (50 mg/kg) once daily for 7 days after the induction of SAH. Double immunofluorescence staining was used to verify proliferation, differentiation and migration of progenitor cells. Rotarod test and water maze used to test the neurobehavioral recovery. ResultsOur results showed that BrdU positive cells in hippocampus changed overtime after SAH. BrdU positive cells decreased as early as 1 day reaching lowest levels at 3 days after SAH, after which it gradually recovered. Similar change patterns were observed with DCX, which was reversed with GFAP. In addition, BrdU did not co-localize with cleaved caspase-3. The BrdU positive cells mainly differentiated into immature neurons for short-term fate, whereas they differentiated into mature neurons for long-term fate but not astrocytes, which facilitated neurobehavioral recovery after SAH. ConclusionNeurogenesis in the hippocampus changes overtime after SAH. The neuronal progenitor cells may play an essential role in the neurobehavioral recovery after brain injury induced by SAH, since short-term progenitors helped with the recovery of immature neurons in the hippocampus, whereas long-term progenitors differentiated into mature neurons.

DNA methylation and histone deacetylation regulating insulin sensitivity due to chronic cold exposure

In this study, we investigated the causal relationship between chronic cold exposure and insulin resistance and the mechanisms of how DNA methylation and histone deacetylation regulate cold-reduced insulin resistance. 46 adult male mice from postnatal day 90–180 were randomly assigned to control group and cold-exposure group. Mice in cold-exposure group were placed at temperature from -1 to 4 °C for 30 days to mimic chronic cold environment. Then, fasting blood glucose, blood insulin level and insulin resistance index were measured with enzymatic methods. Immunofluorescent labeling was carried out to visualize the insulin receptor substrate 2 (IRS2), Obese receptor (Ob-R, a leptin receptor), voltage-dependent anion channel protein 1 (VDAC1), cytochrome C (cytC), 5-methylcytosine (5-mC) positive cells in hippocampal CA1 area. Furthermore, the expressions of some proteins mentioned above were detected with Western blot. The results showed: ① Chronic cold exposure could reduce the insulin resistance index (P < 0.01) and increase the number of IRS2 positive cells and Ob-R positive cells in hippocampus (P < 0.01). ② The expressions of mitochondrial energy-relative proteins, VDAC1 and cytC, were higher in cold-exposure group than in control group with both immunohistochemical staining and Western blot (P < 0.01). ③ Chronic cold exposure increased DNA methylation and histone deacetylation in the pyramidal cells of CA1 area and led to an increase in the expression of histone deacetylase 1 (HDAC1) and DNA methylation relative enzymes (P < 0.01). In conclusion, chronic cold exposure can improve insulin sensitivity, with the involvement of DNA methylation, histone deacetylation and the regulation of mitochondrial energy metabolism. These epigenetic modifications probably form the basic mechanism of cold-reduced insulin resistance.

Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice

Ethnopharmacological relevanceXiaochaihutang (XCHT), a famous Chinese herbal formula which consists of seven Chinese herbs, has been used clinically in depressive disorders in China. Our previous studies have demonstrated that XCHT improved depressive-like behavior in several animal models of depression. However, therapeutic basis of XCHT on depression are challenging, due to the complex active constituents of XCHT and the unclear pharmacological mechanism of action. Materials and methodsTo provide further insights into therapeutic basis of XCHT, the core in compatibility of XCHT on antidepressant therapy was assessed by the method of orthogonal array design. The comparative evaluations on antidepressant effects of XCHT and its core in compatibility were executed by tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSFT), reserpine-induced hypothermia and palpebral ptosis. Moreover, the potential mechanism was explored by investigating levels of monoamine neurotransmitters in hypothalamus and striatum and neurogenesis in hippocampus. Chemical profile of active constituents in plasma after oral administration of the core in compatibility of XCHT was revealed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). ResultsThe results of orthogonal array design experiment showed that Huangqin (Radix scutellariae), Renshen (Ginseng) and Gancao (Radix glycyrrhizae), defined as HRG, might be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, oral administration of HRG for 15 days significantly reduced immobility duration in TST and FST without affecting locomotor activity. Both HRG and XCHT increased immobility latency in FST, decreased the latency in NSFT, reversed reserpine-induced hypothermia and palpebral ptosis. Moreover, both HRG and XCHT significantly increased levels of 5-HT and DA in hypothalamus. In addition, HRG could remarkably increase Ki-67 and doublecortin (DCX) positive cells in hippocampus. A total 25 active constituents in plasma, including 14 prototype components and 11 metabolites, were identified by UPLC–MS/MS after oral administration of HRG. ConclusionThe present results reveal that HRG is supposed to be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, HRG exerts significant antidepressant-like effects, which are likely attributed to regulating serotonergic and dopaminergic systems and increasing hippocampal neurogenesis. The constituents identified in plasma after oral administration of HRG may be the potential active ingredients for the treatment of depression.

Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia.

Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.

Neuroprotection with Glycine-2-Methylproline-Glutamate (G-2MePE) after hypoxic-ischemic brain injury in adult rats

Background and Purpose: Hypoxic-ischemic brain injury, due to reduced supply of oxygen to brain, is a major cause of death and disability. There is no exclusive treatment available so far. Glycine-2-Methylproline-Glutamate (G-2MePE, NNZ 2566), an analogue of Glycine-Proline-Glutamate reduces neuronal injury after focal ischemia in adult rats. The current study investigated into the neuroprotective effects of G-2MePE after global hypoxic-ischemic brain injury in adult rats.Methods: Adult male rats received a single sub cutaneous injection of G-2MePE (1.2mg/kg) 3h post hypoxic-ischemic brain injury or the same volume of normal saline. Brains were extracted 5 days after the treatment. Tissue damage in the cortex, hippocampus and striatum was assessed. Neuronal survival, glial reactions, caspase-3 activity and TNF-α cytokine activity were also assessed.Results: The treatment with G-2MePE was associated with a significant reduction of tissue damage, improvement in neuronal survival, reduction in reactive microglia, TNF-α positive cells and caspase-3 positive cells in hippocampus and cortex but an elevation of astrocytosis.Conclusions: Neuroprotection with G-2MePE after hypoxic-ischemic brain injury in adult rats is associated with reduced neuronal necrosis, apoptosis, modulated inflammatory responses and augmented astrocytosis.

RETRACTED: Acute ethanol administration affects memory reactivation: A look at the neuronal density and apoptosis in the rat hippocampus

This study is an attempt to examine whether administration of ethanol after memory reactivation will modulate expression of memory in rats or not. We further examined whether this administration alters the number of tunnel positive cells in hippocampus. Adult male Wistar rats were trained in a fear conditioning system using two 1s , 0.6 mA shock with an interval of 180 s. 24 h later the rats were returned to the chamber for reactivation, and then they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline, ip. Again, one, seven and fourteen days after reactivation, the rats were returned to the context for 5 min. The freezing time (absence of all movements except respiration) was scored in seconds. In the second experiment, after test 1, the animals were anesthetized and a transcardial perfuse with phosphate buffer and paraformaldehyde 4% was conducted. After post-fixation of brains 5-μm sections were stained with cresyl violet. Finally, paraffin-embedded sections of 10 μm were cut out throughout the tissue and each sample was processed with TUNEL. The number of apoptotic cells in a 130 μm-long segment of the hippocampal CA1 and CA3 fields and dentate gyrus was counted. The data demonstrate that ethanol exposure impairs post retrieval processes. Rats receiving ethanol (1.5 mg/kg) showed lower freezing levels during the first test. Moreover, ethanol decreases the density of CA1, CA3 and DG cells and increases the density of apoptotic cells in all regions of hippocampus. Therefore, ethanol exposure impairs reconsolidation of contextual fear conditioning probably via decreasing the density of CA1, CA3 and DG cells.

P75 neurotrophin receptor regulates basal and fluoxetine-stimulated hippocampal neurogenesis

It is widely acknowledged that neurogenesis occurs in the adult hippocampus under normal conditions and that the rate can be regulated by environmental factors, including antidepressant drugs, with concomitant effects on behaviour. Using a quick and sensitive flow cytometry method that can assess changes in the number of bromodeoxyuridine (BrdU)-positive cells in hippocampus, in combination with traditional histological cell counts in the dentate gyrus, we report that mice lacking the p75 neurotrophin receptor gene (p75(NTR-/-)) have significantly reduced hippocampal neurogenesis. Chronic treatment with the antidepressant fluoxetine stimulated hippocampal cell proliferation in p75(NTR-/-) animals, but it did not result in an increase above basal levels of the number of newly born neurons in the dentate gyrus. These results indicate that p75(NTR) acts as a regulator of fluoxetine-stimulated as well as basal adult hippocampal neurogenesis.

Nortriptyline mediates behavioral effects without affecting hippocampal cytogenesis in a genetic rat depression model

A prevailing hypothesis is that neurogenesis is reduced in depression and that the common mechanism for antidepressant treatments is to increase it in adult hippocampus. Reduced neurogenesis has been shown in healthy rats exposed to stress, but it has not yet been demonstrated in depressed patients. Emerging studies now indicate that selective serotonin reuptake inhibitors can, exert behavioral effects without affecting neurogenesis in mice. Here we extend our previous findings demonstrating that the number of BrdU positive cells in hippocampus was significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to the control strain the Flinders Resistant Line (FRL). We also show that chronic treatment with the tricyclic antidepressant nortriptyline exerts behavioral effects in the Porsolt forced swim test without affecting hippocampal cell proliferation in the FSL model. These results strengthen the arguments against hypothesis of neurogenesis being necessary in etiology of depression and as requisite for effects of antidepressants, and illustrate the importance of using a disease model and not healthy animals to assess effects of potential therapies for major depressive disorder.

Relationship between post‐traumatic stress disorder‐like behavior and reduction of hippocampal 5‐bromo‐2′‐deoxyuridine‐positive cells after inescapable shock in rats

Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors.

Transducible P11-CNTF rescues the learning and memory impairments induced by amyloid-beta peptide in mice

Alzheimer's disease is a progressive brain disorder with the loss of memory and other intellectual abilities. Amyloid species and neurofibrillary tangles are the prime suspects in damaging and killing nerve cells. Abnormal accumulation of Amyloid-beta peptide (Aβ) may cause synaptic dysfunction and degeneration of neurons. Drugs that can prevent its formation and accumulation or stimulate its clearance might ultimately be of therapeutic benefit. Ciliary neurotrophic factor (CNTF), a neurotrophic cytokine, promotes the survival of various neurons in brain. However, the blood-brain barrier hinders the systemic delivery of CNTF to brain. Recently the 11-amino acid of protein transduction domain TAT has successfully assisted the delivery of many macromolecules to treat preclinical models of human disease. The present study aimed to evaluate whether P11-CNTF fusion protein (P11-CNTF) is protective against the Aβ25-35-induced dementia in mice. Immunofluorescence experiments showed that P11 effectively carried CNTF to the SH-SY5Y cells in vitro, and to the brains of mice in vivo. The learning and memory impairments of mice induced by Aβ were substantially rescued by supplement with the P11-CNTF. Furthermore, mRNAs of enzymes involved in the Aβ metabolism, e.g. neprilysin (NEP), endothelin-converting enzyme 1 (ECE-1) and insulin degrading enzyme (IDE), increased in the P11-CNTF treated dementia mice, accompanied by the proliferation of nestin- and choline acetyltransferase (ChAT)-positive cells in hippocampus. It implies that the delivery of P11-CNTF may be a novel treatment for Alzheimer's disease.

Escitalopram reduces increased hippocampal cytogenesis in a genetic rat depression model

Hippocampal neurogenesis is potentially implicated in etiology of depression and as the final common mechanism underlying antidepressant treatments. However, decreased neurogenesis has not been demonstrated in depressed patients and, in animals, reduced cytogenesis was shown in healthy rats exposed to stressors, but, so far, not in models of depression. Here we report that the number of BrdU positive cells in hippocampus was (1) significantly higher in a rat model of depression, the Flinders Sensitive Line (FSL) compared to control FRL, (2) increased in both FSL and FRL following maternal separation, (3) reduced by escitalopram treatment in maternally separated animals to the level found in non-separated animals. These results argue against the prevailing hypothesis that adult cytogenesis is reduced in depression and that the common mechanism underlying antidepressant treatments is to increase adult cytogenesis. The results also point to the importance of using a disease model and not healthy animals for testing effects of potential treatments for human depression and suggest other cellular mechanisms of action than those that had previously been proposed for escitalopram.

택지개발 현장 내 비위생매립지의 매립쓰레기 처리방안 연구

China is one of countries with the highest mercury production in the world. The Guizhou Province in Southwestern China is currently one of the world's most important mercury production areas. In order to study the neurotoxicity of rice from Qingzhen Chemical Plant area and probe into the signal transduction molecular mechanism of injury in rat brain stimulation by mercury contaminated rice. The rats were exposed to mercury contaminated rice for 20 d. Both of the measurements of NO and NOS were processed according to the protocol of the kit. The effect of Hg contaminated rice on the expression of c-fos mRNA in rat brain and the expression of c-FOS protein in cortex, hippocampus were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The results showed the neural transmitter NO and NOS in brain were significantly change between exposure groups and control group; the mercury polluted rice induced significantly the expression of c-fos mRNA; the c-FOS positive cells in hippocampus and cortex of exposure groups were significant different from control group (p < 0.01). It could be concluded that nitric oxide was involved in mercury contaminated rice induced immediate early gene c-fos expressions in the rat brain. Through food chain, local ecosystem and health of local people iave been deteriorated seriously by mercury. This serious situation will last a long period. In order to alleviate mercury pollution, more work needs to do.