ABSTRACT
ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.
ABSTRACT
Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.
Subject(s)
Animals , Mice , Epilepsy/metabolism , Kinesins/metabolism , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Seizures/metabolismABSTRACT
@#Chronic pain is a debilitating condition that occurs after tissue damage, which substantially affects the patient’s emotional state and physical activity. The chronic pain in rheumatoid arthritis (RA) is the result of various autoimmune-induced inflammatory reactions in the joints. Both types of peripheral and central pain processing can lead to sensitisation. Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) can result in potent anti-inflammatory effect. However, these drugs are not able to suppress the pain from RA for a prolonged period. For years, researchers have examined the role of the N-methyl-D-aspartic acid receptor 2B (NR2B) subunit of N-methyl-D-aspartate receptors (NMDAR) in chronic and neuropathic pain models. This NMDAR subtype can be found in at the peripheral and central nervous system and it represents an effective therapy for RA pain management. This review focuses on the NR2B subunit of NMDAR and the different pathways leading to its activation. Furthermore, specific attention is given to the possible involvement of NR2B subunit in the peripheral and central pathogenesis of RA.
ABSTRACT
Aim To investigate the improving effect of transcranial direct current stimulation (tDCS) on endogenous hippocampal neurogenesis in mice with cerebral ischemiaand the possible mechanism. Methods The model of acute cerebral ischemia in mice was established by bilateral common carotid artery occlision (BCCAO). The pathological changes of mice were detected by hippocampal HE staining. The learning and memory function of mice was assessed by Morris water maze. The number of BrdU, DCX and BrdU/NeuN-positive cells was observed through immunofluorescence staining for detecting hippocampal neurogenesis. The mRNA and protein expressions of NMDAR subunits NR2a and NR2b in hippocampus were detected by qRT-PCR and Western blot. Results The neuronal damage in the hippocampal CA1 region was marked (P <0. 01), and the learning and memory function significantly decreased (P<0. 01) in cerebral ischemia mice, suggesting the successful establishment of cerebral ischemia model. At the same time, the number of BrdU, DCX and BrdU/NeuN positive cells was up-reg-ulated significantly (P < 0. 01 ) , indicating the occurrence of neurogenesis in hippocampus after cefebral ischemia. Treatment with tDCS significantly ameliorated the pathological damage in CA1 region of mice, improved learning and memory, and promoted hippocam-pal neurogenesis. Meanwhile, the mRNA and protein expression levels of NR2a and NR2b in hippocampus were also up-regulated (P < 0. 05 or P < 0.01). Conclusions tDCS can promote hippocampal neurogenesis and improve learning and memory function in cerebral ischemia mice, which may be related to theup-regula-tion ofNR2a and NR2b expression.
ABSTRACT
Aim To study the effect of ginsenoside Rbl on methamphetamine-induced CPP in rats and to explore the role of NR2B/CREB in it. Methods METH(2mg·kg-1, i.p) was administered to establish METH-induced CPP model in rats. 0 ∼3 d was the adaptation stage and 4 ∼ 13 d was the experimental stage. METH (2 mg · kg-1, i. p) or saline (10 mg · kg-1, i. p) was injected every other day. Rb1 (10 mg · kg-1, i.p) or saline was pre-injected lh before injection of METH or saline. After perfusion, the hippocampus was isolated from brain on ice, and the expression levels of NR2B, CREB and p-CREB were detected by Western blot. Results The animal model of METH-induced CPP was successfully established. The rats were pretreated with Rbl (10 mg · kg-1) for 1 h, and the time that the rats stayed in drug-paired was significantly reduced compared with METH group. Western blot results showed that NR2B, p-CREB and p-CREB/CREB significantly increased in METH group and without altering CREB expression levels compared with control group. However, after pre-treated with Rbl, the expression levels of NR2B, p-CREB and p-CREB/CREB decreased compared with METH group. Conclusions METH can significantly induce CPP in rats. Rbl may inhibit METH-induced CPP in rats by regulating NR2B and p-CREB.
ABSTRACT
BACKGROUND: This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli. METHODS: Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed. RESULTS: DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B. CONCLUSION: We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.
Subject(s)
Animals , Humans , Male , Rats , Diabetes Mellitus , Diabetic Neuropathies , Formaldehyde , Hyperalgesia , N-Methylaspartate , Pain Measurement , Pain Threshold , Phosphorylation , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Spinal Cord , StreptozocinABSTRACT
Objective To observe the effect of Kidney-nourishing, Blood-activating, Phlegm-resolving and Resuscitation-inducing Decoction(KBPRD)on the expression of N-methyl-D-aspartate(NMDA)receptor subtype 1,2A,2B(NR1,NR2A,NR2B)in the cochlear spiral ganglion neurons(SGN)of tinnitus rats and to explore its mechanism, thus to provide experimental evidence for the treatment of tinnitus with KBPRD. Methods Sixty rats were randomly divided into normal group,model group,western medicine group,and low-,middle-,and high-dose Chinese medicine groups, 10 rats in each group. Rats were given intraperitoneal injection of sodium salicylate combined with water deprivation to induce tinnitus model. After successful establishment of the model, the rats in low-,middle-,and high-dose Chinese medicine groups were given gastric administration of KBPRD in the dosage of 5.5, 11, 22 g·kg-1·d-1 respectively, the rats in western medicine group were given gastric administration of 5 mg·kg-1·d-1 of carbamazepine,and rats in the model group and normal group were given gastric administration of 2 mL of normal saline,once every day,treatment time covering 8 weeks. The expression levels of NR1,NR2A,and NR2B in the cochlear SGN was detected by immunoblotting and real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR)after 8 weeks of treatment. Results Compared with the normal group,the expression levels of NR1, NR2A and NR2B in the model group were increased, the difference being significant (P < 0.05). Compared with the model group,the expression of NR1,NR2A and NR2B in low-,middle-,and high-dose Chinese medicine groups were significantly decreased(P<0.05).Conclusion KBPRD is effective on relieving tinnitus of rats, and its mechanism is correlated with lowering the increased expression of NR1,NR2A and NR2B in SGN of tinnitus rats.
ABSTRACT
Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.(AU)
Subject(s)
Computer Simulation , Receptors, Glutamate , Alzheimer Disease , Neuronal Plasticity , Neurotransmitter AgentsABSTRACT
Abstract Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimers disease.
ABSTRACT
Objective To evaluate the role and mechanism of ifenprodil, which is the selective antagonist of N-methyl-D-aspartic acid subtype receptor NR2B, in soflurane-induced cognitive dysfunction in neonatal rats.Methods Twenty-eight 7-day-old Sprague Dawley rats, weighing 15-18 g, were randomly divided into 4 groups (n=7 each): control group (group C), ifenprodil group (group I), sevoflurane group (group S) and ifenprodil+sevoflurane group (group IS).Normal saline 0.2 ml was injected intraperitoneally in group C.Specific NR2B receptor antagonist ifenprodil 5 mg/kg was injected intraperitoneally at the corresponding time points in group I.Normal saline 0.2 ml was injected intraperitoneally and 2.0% sevoflurane was inhaled for 4 h in group S.Ifenprodil 5 mg/kg was injected intraperitoneally 2 h before sevoflurance inhalation, and 2.0% sevoflurance was inhaled for 4 h in group IS.The rats were then sacrificed 3 weeks after administration, their brains were immediately removed and hippocampal slices were prepared for electrophyisological experiments.The value of population spike amplitude (PSA) and long-term potentiation (LTP) were measured every 10 minutes.Induced LTP was recorded.Results Compared with group C, the values of PSA and rates of induced LTP were significantly decreased in group S (P＜0.01).The values of PSA and rates of induced LTP were significantly increased in group IS than those in group S (P＜0.01).Conclusion NR2B receptor is involved in sevoflurance-induced cognitive dysfunction in the neonatal rats.Pretreatment with ifenprodil 5.0 mg/kg can improve the neurotoxicity and protect the brain.
ABSTRACT
Objective We used peptide array technique to construct a peptide FynP inhibiting the interac-tion between Fyn and PSD95 in vitro therefor with a potential for inbiting NR2B phosphorylation level(p-NR2B). This experiment was designed to examine whether FynP(deliverd with TAT-LK15)can inhibit interaction between Fyn and PSD95 in inflammatory pain rats,and therefore inhibit NR2B phosphorylationin in vivo. Methods TAT-LK15 was complexed with FynP(cell-penetrating peptide Tat-LK15/FynP)or scrambled control FynP(Tat-LK15/mFynP). Changes of p-NR2B were detected using western-blot in SCDH of chronic inflammatory pain rats following intraperitoneal injection of Tat-LK15/FynP,meanwhile,the effect of Tat-LK15/FynP on the interaction between Fyn and PSD-95 was tested by co-immunoprecipitation. Pain control efficacy was evaluated by changes of mechani-cal withdrawal threshold(MWT)and thermal withdrawal duration(TWL)in these rats. Results Interaction be-tween Fyn and PSD-95 was efficiently inhibited by intraperitoneal injection of TAT-LK15/FynP complexes while in-jection of FynP or TAT-LK15/mFynP complexes did not show this inhibitory effect. NR2B phosphorylation level was also inhibited by injection of TAT-LK15/FynP,and the changes of p-NR2B levels were reduced by 52%compared to chronic inflammatory pain rats without treatment. FynP or TAT-LK15/mFynP did not show this effect. Moreover, injection of TAT-LK15/FynP complexes significantly reduced MWT and increased TWL of chronic inflammatory pain rats accordingly. Conclusion FynP delivered by Tat-LK15 can perturb Fyn and PSD95 interaction and then inhibit NR2B phosphorylation activation therfor relieve chronic inflammatory pain.
ABSTRACT
Objective We used peptide array technique to construct a peptide FynP inhibiting the interac-tion between Fyn and PSD95 in vitro therefor with a potential for inbiting NR2B phosphorylation level(p-NR2B). This experiment was designed to examine whether FynP(deliverd with TAT-LK15)can inhibit interaction between Fyn and PSD95 in inflammatory pain rats,and therefore inhibit NR2B phosphorylationin in vivo. Methods TAT-LK15 was complexed with FynP(cell-penetrating peptide Tat-LK15/FynP)or scrambled control FynP(Tat-LK15/mFynP). Changes of p-NR2B were detected using western-blot in SCDH of chronic inflammatory pain rats following intraperitoneal injection of Tat-LK15/FynP,meanwhile,the effect of Tat-LK15/FynP on the interaction between Fyn and PSD-95 was tested by co-immunoprecipitation. Pain control efficacy was evaluated by changes of mechani-cal withdrawal threshold(MWT)and thermal withdrawal duration(TWL)in these rats. Results Interaction be-tween Fyn and PSD-95 was efficiently inhibited by intraperitoneal injection of TAT-LK15/FynP complexes while in-jection of FynP or TAT-LK15/mFynP complexes did not show this inhibitory effect. NR2B phosphorylation level was also inhibited by injection of TAT-LK15/FynP,and the changes of p-NR2B levels were reduced by 52%compared to chronic inflammatory pain rats without treatment. FynP or TAT-LK15/mFynP did not show this effect. Moreover, injection of TAT-LK15/FynP complexes significantly reduced MWT and increased TWL of chronic inflammatory pain rats accordingly. Conclusion FynP delivered by Tat-LK15 can perturb Fyn and PSD95 interaction and then inhibit NR2B phosphorylation activation therfor relieve chronic inflammatory pain.
ABSTRACT
Objective To observe the changes of N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B) expression in the striatum of chronic alcohol exposured rats at different withdrawal time.Methods 72 male Wistar rats were randomly divided into withdrawal 2h group,withdrawal 6h group,withdrawal 12h group,withdrawal 1d group,withdrawal 3d group and control group,and 12 rats in each group.In the 5 withdrawal groups,ethanol was administered in drinking water at the concentration of 6％ (V/V) for 16 weeks,and rats in control group were maintained with water.After 16 weeks ethanol was removed and ethanol withdrawal syndromes were evaluated.The expression of NR2B protein in the striatum was measured by immunofluorescence and western blot and the expression of NR2B mRNA in the striatum was measured by realtime PCR.Results Compared with withdrawal scores of control group((1.50±0.80)),scores of withdrawal 2h,6h,12h,1d,3d groups ((10.42±2.50),(15.42± 1.93),(9.25±2.01),(7.67± 1.92),(2.25±0.87) respectively) were higher,and the withdrawal scores of withdrawal 6h group were the highest.Compared with the expression of NR2B fluorescence intensity (2210.00± 178.20),the expression of NR2B protein(0.150±0.009) and the expression of NR2B mRNA(0.006±0.001) in the striatum of control group,the expression of NR2B fluorescence intensity (2710.56 ± 194.21),(5035.16 ± 234.41),(3326.23 ± 378.16),(2570.64 ±177.88),the expression of NR2B protein (0.192±0.008),(1.649±0.205),(0.783±0.109),(0.180±0.009) and the expression of NR2B mRNA (0.026±0.002),(0.351±0.034),(0.248± 0.023),(0.024±0.003) of withdrawal 2h,6h,12h,ld groups were significantly higher (P＜0.05),and with the extension of the withdrawal time,the expression was gradually increased.The expression of withdrawal 6h group was the highest,then began to decline,and returned to baseline levels at withdrawal 3 d(P＞0.05).Withdrawal scores were positively correlated with the expression of NR2B protein(r=0.719,P＜0.01),the expression of NR2B protein was positively correlated with the expression of NR2B mRNA(r=0.937,P＜0.01),and the expression of NR2B mRNA was positively correlated with withdrawal scores(r=0.673,P＜0.01).Conclusion The expression of NR2B was up-regulated in the striatum of chronic alcohol exposured rats at different withdrawl time.NR2B protein and NR2B mRNA expression is positively correlated with the withdrawal scores,suggesting that regulating the expression of NR2B may be a new target for the treatment of ethanol withdrawal symptoms.
ABSTRACT
Objective To observe the effects of acupuncture on synaptic transmission signal molecules in rats with vascular dementia (VD), such as PKC, CaMKⅡ and NR2B, and discuss the molecular mechanism of acupuncture treatment for VD.Methods The multi-infarct dementia model was established by injection of emboli into the internal carotid artery. Experimental rats were randomly divided into normal group, model group, acupuncture group and non-acupoint group. For acupuncture group, acupuncture needles were penetrated into bilateral Zusanli. Non-acupoint group was given acupuncture treatment at the bilateral hypochondrium (10 mm above iliac crest). The rats in normal group and model group were performed to the same amount of capture stimulation as the acupuncture and non-acupoint groups. After treatment, the hippocampal PKC activity was detected by ELISA. Western blot was used to detect CaMKⅡ expression, and the protein expression of NR2B in CA1, CA3 and DG zones was assayed by immunohistochemical staining.Results Compared with normal group, PKC activity and NR2B expression in the hippocampus significantly decreased in the model group (P<0.01). After the acupuncture treatment, PKC activity increased significantly (P<0.05), and the protein expression of NR2B showed a trend to increase. There was no obvious difference in CaMKⅡ expression among all groups.Conclusion Acupuncture at Zusanli can enhance the activity of hippocampal PKC, a synaptic transmission signal molecule, which maybe one of the important molecular targets for the treatment of VD.
ABSTRACT
Objective To investigate the effect of bone cancer pain on emotion and NMDA re-ceptor NR2B subunit expression level in anterior cingulate cortex (ACC)in rats.Methods One hun-dred and fifty healthy male Wistar rats weighing 200-250 g aged 3 months old were randomly divided into 3 groups (n = 50 in each group):sham operation group (group S),bone cancer pain group (group BCP),RO25-6981 group (group RO).The BCP model was established by inoculating Walker 256 breast cancer cells into right intra-tibial.Rats in group S were given the same dose of d-hanks. Group RO was injected intraperitoneally with RO25-6981 (5 mg/kg/d)on the day of inoculation, while rats in the group S and group BCP were given the same dose of normal saline.Mechanical with-drawal threshold (MWT)and thermal withdrawal latency (TWL)of right hind legs were measured on day 7,10,14 after inoculation respectively.Elevated plus-maze test was carried out to investigate the effect of bone cancer pain on emotion in rats after pain threshold detection,then the percentage of the times entering the open arms (OE)and the percentage of the time staying in the open arms (OT) duration the total period were evaluated.Then the anterior cingulate cortex tissue was removed to e-valuate the NR2B protein and mRNA expression levels by RT-PCR,Western blot and immunofluo-rescence methods on day 14 after elevated plus-maze test.Results All the parameters did not differ with significant difference between group S and group RO.MWT decreased and TWL shortened on day 7,10,14 after inoculation in group BCP compared with those before inoculation and those of group S and group RO.OE and OT in group BCP reduced remarkably than those before inoculation and those of group S and group RO.Relative absorbance of NR2B mRNA,the expression of NR2B pro-tein,average NR2B relative fluorescence intensity value is obviously higher than that of group S and group RO (P <0.05).Conclusion Bone cancer pain can induce pain-related aversion and anxiety-like behavior of rats,and the mechanism may be related to the high expression of NR2B in anterior cingu-late cortex.
ABSTRACT
Objective To observe the behavioral and the histopathology changes and expression of NR2B subunit in spinal dorsal horn in chronic constriction injury (CCI) rats after pulsed radiofrequency (PRF). Methods Forty-eight adult Sprague-Dawley rats were randomly divided into Sham-Sham (SS), Sham-PRF (SP), CCI-Sham (CS) and CCI-PRF (CP) groups. The right sciatic nerves (SNs) of the CS and CP groups were ligated to create the CCI model. For the SS and SP groups, the right SNs were separated without ligation. The CP and SP groups accepted PRF at the ligation site 15 days after modeling, while the electrode was placed in rats in the SS and CS groups without elec-tricity. The hindpaw withdrawal threshold (HWT) was measured before and 3, 7, 11, 15 days after modeling, and 1, 3, 7, 11, 15 days after treatment. The right SNs at ligation sites were assessed with optical microscopic score 15 days after treatment, and the NR2B expression in the L4-6 spinal dorsal horn were determined with Western blotting. Results HWT was significantly shorter in the CS and CP groups than in the SS and SP groups after modeling, and was more in the CP group than in the CS group. Under the optical microscope, the axonal diame-ter and myelin sheath thickness increased in the CP group compared to those in the CS group (P<0.01), the NR2B expression was less in the CP group than in the CS group after treatment (F=10.769, P<0.05). Conclusion PRF may reduce hyperalgesia and repair damaged SNs in CCI-induced neuropathic pain, which may associate with inhibition of the NR2B subunit expression in spinal dorsal horn.
ABSTRACT
ObjectiveTo observe the effect ofZuogui Jiangtang Jieyu Formula on the expressions of glutamate, NR2A and NR2B in hippocampus of diabetic rats with depression;To explore the mechanism of protective effect. Methods Diabetes with depression rat models were established and then were randomly divided into the model group, positive medicine group, high-, medium- and low-doseZuogui Jiangtang Jieyu Formula groups. Normal rats acted as normal group, 16 rats per group. After 28 days of administration, Open-field test was used to detect the behavior of the rats;glutamate content of hippocampus was detected by ELISA;the expressions of NR2A and NR2B in rat hippocampus were detected by immunofluorescence.Results Compared with normal group, automatic activity times of rats in model group decreased significantly (P<0.01);both glutamate content (P<0.01) and expressions of NR2A, NR2B (P<0.01) increased significantly. Compared with the model group, automatic activity times of rats in positive medicine group and high-doseZuogui Jiangtang Jieyu Formula group significantly increased (P<0.01);glutamate content dropped (P<0.01);expressions of NR2A and NR2B decreased (P<0.05).ConclusionZuogui Jiangtang Jieyu Formula can improve depressive behavior of diabetic rats with depression, which may be related to the regulation of glutamate content and expressions of NR2A and NR2B in hippocampus.
ABSTRACT
This study was aimed to observe the effect ofZi-Bu Pi-Yin Recipe (ZBPYR) on the mRNA expressions of NMDA receptor subunits NR1, NR2A, NR2B in different brain regions of spleen-yin deficiency Alzheimer's Disease (AD) model rats. The levels of NR1, NR2A, NR2B mRNA expressions were detected by using RT-PCR method. The results showed that the levels of NR1, NR2A, NR2B mRNA expressions of AD group and spleen-yin deficiency AD group decreased significantly (P < 0.05). The levels of NR1, NR2A, NR2B mRNA expressions of ZBPYR treatment group increased significantly (P < 0.05). It was concluded that the expression levels of NMDAR mRNA in different brain regions of the ZBPYR treatment group increased significantly, which indicated that ZBPYR may up-regulate the protein expressions of NMDAR by increasing the expression levels of NMDAR mRNA, thereby to play the anti-dementia effect.
ABSTRACT
ObjectiveTo discuss the correlation between kidney-deficiency constitution and brain function decline, and material basis of kidney-storing-spirit theory and neurobiology mechanism. Methods By employing the method of “cats scare rats”, composite offspring rat models with deficiency and acquired dystrophy were built, then they were divided into model group,ZuoguiPill group and Yougui Pill group. Blank group was composed from normal pregnant rats. When the intimidation of offspring began,Zuogui Pill andYougui Pill groups received gavage with corresponding doses of medicine, 1 times per day for 2 consecutive months. Model and blank groups received the same amount of normal saline. Exercise capacity was detected by suspension test. Learning and memory capacity was detected by Y maze test. Expressions of NMDA receptor subunits NR2A and NR2B were detected by immunohistochemical method.Results In suspension test, the duration of model group was shorter than blank group (P<0.05), while duration ofZuogui Pill andYougui Pill groups was longer than the model group (P<0.05). In Y maze test, the correct number of model group was less than blank group, and increased significantly after treatment (P<0.05). The optical density of NR2A and NR2B was lower in model group than blank group (P<0.05) and higher inZuogui Pill andYougui Pill groups than model group (P<0.05).ConclusionThe neurobehavioral is abnormal and NMDA receptor expression depresses in rats with kidney- deficiency constitution.ZuoguiPill andYouguiPill can rise NMDA receptor expression and improve brain function of rats, which reveal the correlation between kidney-deficiency constitution and brain function decline, and material basis of kidney-storing-spirit theory and neurobiology mechanism.
ABSTRACT
BACKGROUND: In the central nervous system, interleukin-10 (IL-10) provides trophic and survival effects directly on neurons, modulates neurite plasticity, and has a pivotal importance in the neuronal regeneration in neurodegenerative and neuroinflammatory conditions. This cytokine is primarily produced by glial cells and has beneficial effects on the neuronal viability. However, the mechanisms of IL-10-elicited neuroprotection are not clear. RESULTS: Membrane preparations, isolated from wild-type (Wt) and IL-10 knockout (KO) mice brain were used in this study. It has been shown that compared to wild-type mice, in IL-10 KO mice brain, the amount of immunoglobulin binding protein (BiP) is greatly increased, whereas the content of sigma receptor-1 (SigR1) is not changed significantly. Co-immunoprecipitation experiments have shown that the association of SigR1 with small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1), NR2B subunit of NMDA-receptor (NMDAR) and inositol-3-phosphate receptor (IP3R) is higher in the IL-10 KO mice brain than in the Wt mice brain. Besides, we have found that either glutamate or sigma ligands, separately or together, do not change glutamate-induced NADPH-oxidase (NOX) activity in Wt-type mice brain membrane preparations, whereas in IL-10 KO mice high concentration of glutamate markedly increases the NOX-dependent production of reactive oxygen species (ROS). Glutamate-dependent ROS production was decreased to the normal levels by the action of sigma-agonists. CONCLUSIONS: It has been concluded that IL-10 deprivation, at least in part, can lead to the induction of ER-stress, which causes BiP expression and SigR1 redistribution between components of endoplasmic reticulum (ER) and plasma membrane. Moreover, IL-10 deficiency can change the specific organization of NMDAR, increasing the surface expression of SigR1-sensitive NR2B-containing NMDAR. In these conditions, glutamate-dependent ROS production is greatly increased leading to the initiation of apoptosis. In this circumstances, sigma-ligands could play a preventive role against NMDA receptor-mediated excitotoxicity.