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Objective:To explore the protective effects and mechanisms of L-carnitine (LCAR) on cognitive dysfunction in chronic cerebral hypoperfusion rats.Methods:Totally 90 SD male rats (SPF class) aged 3-4 months were divided into four groups according to random number talbe: sham operated control group (SHAM group, n=15), sham operated with L-carnitine treatment group (LCAR group, n=25), 2-vessel occlusion group (2VO group, n=25), and 2-vessel occlusion with L-carnitine treatment group (2VO+ LCAR group, n=25). The chronic cerebral hypoperfusion model was established by bilateral common carotid artery ligation, and the carotid arteries from SHAM group and LCAR group were only separated without ligation.L-carnitine was administered intraperitoneally (300 mg·kg -1·d -1) for 30 days after surgery in the LCAR and 2VO+ LCAR groups.After 30 days of L-carnitine intervention, Morris water maze was performed to test the spatial cognitive function of the rats, the ATP level of hippocampal tissue was detected by chemiluminescence, the mitochondrial structure and synaptic structure of hippocampal neurons were observed by transmission electron microscopy, the degree of mitochondrial damage was scored, the vesicle density was counted and measured, the level of N-methyl-D-aspartate receptor subunit 2A or 2B(NR2A/B) and postsynaptic density 95(PSD95) in hippocampal tissue were detected by Western blot.The expression and distribution levels of transcription factor cAMP response element-binding protein(CREB) in brain tissues were observed by immunofluorescence.SPSS 16.0 software was used for statistical analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA, while other data were adopted by one-way ANOVA, and Dunnett's t test was used for further pairwise comparison. Results:(1)Morris water maze results showed that the time and group interaction of escape latency was not significant among the 4 groups of rats ( F=1.4, P>0.05), but the time main effect and group main effect were significant( F=21.6, 15.2, both P<0.05). Morris water maze results showed that platform position learning from 3rd to 7th day, the escape latencies in 2VO group were longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). The results of short-term memory showed that the escape latency in 2VO group was longer than those in SHAM group and 2VO+ LCAR group (all P<0.05). Meanwhile, the retention time and crossing times in the platform area of 2VO group were less than those in SHAM group and 2VO+ LCAR group (all P<0.05). (2) The absolute and relative levels of ATP in hippocampus showed that the difference among the 4 groups were statistically significant ( F=14.6, 13.2, both P<0.05). ATP level of hippocampus in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.05). Electron microscopic observation of mitochondrial morphology showed that the Flameng score of mitochondrial damage in the hippocampus of rats in 2VO group (2.82±0.17) was higher than those in SHAM group (0.25±0.07) and 2VO+ LCAR group (1.76±0.09) (both P<0.05). (3) The density of synaptic vesicles in the hippocampus of rats in 2VO group ((289.09±22.41)/μm 2)was lower than those in SHAM group ((497.49±28.89)/μm 2)and 2VO+ LCAR group ((401.23±45.09)/μm 2) (both P<0.01). Western blot results showed that the relative levels of synaptic proteins NR2A/B, PSD95 and CREB in 2VO group were lower than those in SHAM group and 2VO+ LCAR group (all P<0.05). Immunofluorescence results showed that the relative level of CREB expression in hippocampal subregions and cortex in 2VO group was lower than those in SHAM group and 2VO+ LCAR group (both P<0.01). Conclusion:L-carnitine can improve spatial learning and memory dysfunction in rats with chronic cerebral hypoperfusion, which are related with promoting ATP production and protecting mitochondrial morphology, and promoting synaptic vesicle synthesis and synaptic protein expression.
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Ischemic stroke is a common disease of the nervous system, which is characterized by high incidence, recurrence, disability and mortality rate. The pathological mechanism of ischemic brain injury is complex. Synaptic plasticity injury is considered to be the earliest pathological change after cerebral ischemia, and regulating synaptic plasticity is one of the important mechanisms to promote the recovery of neurological function after stroke. This article reviews the advances in synaptic plasticity after ischemic brain injury, which provides theoretical basis for the development of neuroprotective drugs in the future.
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Memory loss induced by aging and hypoxia is very common, so exploring the mechanism of memory production, storage and retrieval is of great significance to daily life and clinical work. The storage and retrieval of memory is probably similar to the computer. We summarized the research progress of MeshCODE theory, the mechanical basis of memory. Memory loss in certain diseases (such as Alzheimer's disease) or pathological conditions (such as aging, lack of oxygen) may be associated with abnormal folding of talin, a mechanosensitive protein. It can dynamically regulate synaptic activity by changing the state of the domain, storing or updating information about small changes in mechanical forces in binary form, and initiating chemical processes such as ligand redistribution in neurons, so that memory is stored in the brain in a binary format, known as the MeshCODE theory.
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OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.
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Animals , Mice , Aspartic Acid/metabolism , Cerebral Cortex , Dendritic Spines/metabolism , Neurons/metabolism , Synapses , Tryptophan/metabolismABSTRACT
Objective:To explore the protective effect of α-lipoic acid (LA) on radiation damage of mice cochlear ribbon synapses.Methods:Mice were divided into five groups: control group, radiation 3 d group, radiation 3 d+ LA group, radiation 14 d group and radiation 14 d+ LA group. The radiation groups were irradiated with 16 Gy, the radiation+ LA groups were given LA once a day after radiation, the control group was given the same amount of normal saline. The auditory brainstem response (ABR) of mice were measured before irradiation and sacrifice. The number of ribbon synapses were observed with immunofluorescently labeled protein ctBP2. Western blot assay was performed to obtain the semi-quantitative expression levels of otoferlin and AP-2 protein.Results:Compared with the control group, the ABR threshold of radiation groups were significantly higher ( P<0.05) with the highest value at 14 d after irradiation ( P<0.05), and the ABR threshold of the radiation+ LA groups were significantly lower ( P<0.05). The ABR threshold shifts of 12 kHz, 24 kHz at 3 d and 14 d groups had no significant difference with 8 kHz threshold shift ( P>0.05). The 32 kHz threshold shift was significantly higher than 8 kHz threshold shift ( t=-2.38, -5.48, P<0.05). The number of ribbon synapses in the radiation groups was significantly lower than that of control group ( P<0.05), with the lowest value in the radiation 14 d group. LA treatment increased the ABR value significantly ( P<0.05). AP-2 and otoferlin protein levels were significantly reduced after irradiation, especially in the radiation 14 d groups, and they were increased by the LA treatment. Conclusions:LA has protective effect on the ribbon synapses of cochlear hair cells.
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Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
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Objective@#To investigate the impact of hypoxic-ischemic brain injury (HIBI) on brain development in neonatal rats of different sexes.@*Methods@#From January 1 to December 31, 2018, 60 7-day-old SD rats were randomly divided into HIBI-F group (20 rats), HIBI-M group (20 rats), and control group (20 rats, 10 females and 10 males). The animal model of HIBI was established with Rice-Vannucci method, with the rats′ left common carotid artery double-ligated and severed. The rats were then placed in an incubator and exposed to a hypoxic gas mixture (8% O2, 92% N2) for 90 minutes. No intervention was given to the control group. Two weeks after HIBI, the motor development was evaluated by footprint analysis, the residual brain volume was measured by brain magnetic resonance imaging (MRI), and the damage of synaptic ultra structure was analyzed by transmission electron microscope. One-way ANOVA or χ2 test was used for inter-group statistical analysis, and paired sample t test was used to compare the bilateral step length and toe distance of rats in the same group.@*Results@#The mortality rate of HIBI-F was significantly higher than that of HIBI-M (20%(4/20) vs. 10%(2/20), χ2=40.000, P=0.001). The right step length and toe distance in HIBI-M group and HIBI-F group were significantly shorter than those in control group ((7.5±0.3) cm and (7.9±0.5) cm vs. (8.2±0.5) cm, F=9.605, P<0.01, (0.9±0.1) cm and (1.0±0.0) cm vs. (1.1±0.1) cm, F=71.437, P<0.01). Besides, according to above data, the right step length and toe distance in HIBI-M group were significantly shorter than those in the HIBI-F group (both P<0.01). Furthermore, the right step length was significantly shorter than the left step length ((8.3±0.4) and (8.3±0.5) cm, t=5.289 and 10.580, P=0.001 and 0.010, respectively) and toe distance ((1.1±0.1) and (1.1±0.1) cm, t=7.953 and 6.435, respectively, both P<0.01) in both HIBI-M group and HIBI-F group. Similarly, the synaptic gap of the left precentral gyrus neurons was longer in HIBI-M group and HIBI-F group than that in control group ((23.4±1.3) and (19.7±1.6) nm vs. (18.9±0.6) nm, F=71.719, P<0.01), and also longer in HIBI-M group than that in HIBI-F group (t=7.645, P<0.01). Likewise, the residual brain volume in HIBI-M group and HIBI-F group was significantly less than that in control group ((67±4)% and (75±5)% vs. 100%, F=406.122, P<0.01), and the residual brain volume in HIBI-M group was significantly less than that in HIBI-F group (t=-5.281, P<0.01).@*Conclusions@#Male neonatal rats are more vulnerable to HIBI and have severer subsequent brain injury and hemiplegia. Different treatment strategies for HIBI patients of different sexes should be developed.
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BACKGROUND: Olfactory ensheathing cell transplantation for treating spinal cord injury is an issue of concern, which mainly explores the changes of microenvironment after spinal cord injury. However, the effect of olfactory ensheathing cell transplantation on the ultrastructure of spinal cord after spinal cord injury is never reported. OBJECTIVE: To investigate the ultrastructure alterations of neurocytes, axons, myelin sheaths, synapses, and glial scar after spinal cord Injury, and the effect of olfactory ensheathlng cell transplantation on the protection and regeneration of nerve repair after spinal cord Injury. METHODS: The study was approved by the Ethical Committee of Biomedicine of Medical Department of Xi’an Jiaotong University, approval No. 2018-2048. Twenty female Sprague-Dawley rats were divided into three groups: Blank control group (n=4, complete laminectomy of T10, partial laminectomy of Tg and Tn), DF12 group (n=B, cordotomy+injection of DF12 solution), and olfactory ensheathing cell transplantation group (n=8, cordotomy+olfactory ensheathing cell transplantation). The spinal cord was removed under anesthesia to observe the ultrastructure alterations of neurocytes under transmission electron microscope at 1, 7, 28 and 56 days after injury. RESULTS AND CONCLUSION: (1) Compared with the blank control group, the organelles in the neurons of the injured lesions were significantly reduced, and the obvious changes were found in the ultrastructure of axon, synapses and myelin sheath in the DF12 group. In the olfactory ensheathing cell transplantation group, the organelles in the neurons of the injured lesions were significantly increased with obvious nucleolus, the regeneration of axon, myelin sheath and synapses were significantly promoted, and the glial scar was significantly decreased. (2) The degree of reaction of the astrocytes and pericytes in the olfactory ensheathing cell transplantation group was light. (3) These findings suggest that olfactory ensheathing cell transplantation can effectively protect the nerve tissues in the lesions after spinal cord injury, promote the regeneration of axon, myelin sheath and synapses, and inhibit the hyperplasia of astrocytes and pericytes, so that the post-injury microenvironment is available for the regeneration of neurons, axons and synapses.
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BACKGROUND: Glial cell line derived neurotrophic factor (GDNF) plays an important role in inducing the differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and promoting the regeneration of neuron axons. OBJECTIVE: To observe BMSCs differentiation induced by over-expression of GDNF gene, detect synaptic function of cells and expression of Wnt signaling pathway components after differentiation, and preliminarily explore the mechanism of BMSCs differentiation into mature neurons. METHODS: Rat BMSCs were isolated and cultured, and further divided into recombinant adenovirus-containing GDNF gene transfection group (Ad-GDNF-BMSCs), adenovirus transfection control group (Ad-BMSCs), and untransfected control group. The relative expression of GDNF gene in BMSCs of each group was detected by Q-PCR, and the expression of β-catenin, cyclin D1, NeuN and MAP-2 was detected by immunofluorescence technology in each group. High K+ stimulation induced cell depolarization response after differentiation, and FM4-64 marks synaptic vesicle activity of differentiated cells. RESULTS AND CONCLUSION: (1) The adenovirus-transfected gene had no significant negative effect on the proliferation of BMSCs. BMSCs could express endogenous GDNF gene continuously and at high levels. (2) Under the induction of GDNF gene, BMSCs could express neuron-specific protein NeuN after 3 days cultivation in vitro. The expression of β-catenin protein also could be detected in the cytoplasm of cells. After 7 days cultivation in vitro culture, BMSCs expressed the mature neuronal marker protein MAP-2, and the cell body contracted significantly. Neuron axon-like structures appeared around the cell body. Moreover, β-catenin and cyclin D1 were respectively detected in the cell cytoplasm and the nucleus, while the expression levels of NeuN, MAP-2, β-catenin, and cyclin D1 were not observed in Ad-BMSCs and untransfected control groups, and the cells remained spindle-shaped. (3) After 11 days of in vitro culture, the cells in the Ad-GDNF-BMSCs group showed typical neuronal processes or axons and connected to each other into a network structure, which could be labeled with FM4-64 to show red fluorescence, and induced by high K+ stimulation to induce action potentials in the cells. Synaptic vesicle activity in posterior axons showed FM4-64 red fluorescence gradually decaying. Under the same conditions, cells in the Ad-GDNF-BMSCs group and untransfected control group did not present FM4-64 fluorescently labeled synaptic vesicle activity. (4) Continuous GDNF induction can promote BMSCs differentiated into mature neurons with synaptic cycle function, and may be carried out through the classic Wnt/β-catenin signaling pathway.
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RESUMEN Introducción: el objeto más complejo descubierto hasta ahora en cualquier parte del universo es el órgano que ocupa el espacio comprendido entre nuestras orejas: el cerebro. No es el elevado número de neuronas individuales lo más relevante del cerebro, sino cómo están organizadas e interconectadas. Objetivo: analizar elementos teóricos y experimentales expuestos en la literatura consultada acerca de los mecanismos de plasticidad cerebral. Métodos: se realizó un estudio descriptivo a partir de una revisión bibliográfica, desde el punto de vista teórico se utilizaron los métodos histórico-lógico, análisis-síntesis e inductivo-deductivo que permitieron el análisis de las principales teorías generadas por diversos estudios experimentales acera del tema en cuestión. Desarrollo: neurocientíficos han estudiado desde entonces este enigma demostrando la existencia por diversos mecanismos de fenómenos que permiten el reordenamiento neuronal y la suplencia de funciones cerebrales en respuesta a diversos eventos patológicos o como resultado del proceso de aprendizaje y memoria. Conclusiones: tanto la experimentación animal como los estudios realizados en humanos con el empleo de modernas técnicas no invasivas respaldan las ideas de plasticidad neuronal.
ABSTRACT Introduction: brain is the most complex organ discovered up to date, due to the organization and interconnection of its individual neurons. Objective: to analyze theoretical and experimental elements stated in the medical literature reviewed about cerebral plasticity mechanisms. Methods: a descriptive study was carried out based on a bibliographic review. From the theoretical point of view historical-logical, analysis-synthesis and inductive-deductive methods were applied, which allowed the analysis of the main theories generated by different experimental studies. Development: it has been demonstrated the existence of diverse mechanisms that allocate the neuronal rearrangement and replacement of cerebral functions, in response to diverse pathological events or as a result of learning and memory process. Conclusions: both animal testing and studies carried out in human being using modern non-invasive techniques support the ideas of neuronal plasticity.
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Auditory neuropathy (AN) is a hearing disorder where cochlear inner hair cell and/or the auditory nerve function is disrupted while outer hair cell function is normal. It can affect people of all ages, from infancy to adulthood. People with auditory neuropathy may have normal hearing threshold, or hearing loss ranging from mild to severe; they always have poor speech-perception abilities. It is a heterogeneous disorder which can have either congenital or acquired causes. AN may result from specific loss of cochlear inner hair cells, disordered release of neurotransmitters by inner hair cell ribbon synapses, deafferentation accompanying loss of auditory nerve fibers, neural dys-synchrony or conduction block as a result of demyelination of nerve fibers and auditory nerve hypoplasia. Although the definition of AN includes the central part, its incidence is low, and the etiology and pathology are not clear. The present review aimed to provide an overview of the genetic conditions associated with AN and highlight the neural and synaptic mechanism of AN. Possible strategy for treatments of AN was also discussed.
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Objective: To investigate the neuroprotective effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on β-amyloid protein 25-35 (Aβ25-35)-induced neuron synapses damage. Method: Primary neurons were isolated and purified from cerebral cortex of suckling mouse. Then neurons were divided into control group, model group (incubation with Aβ25-35) and TSG groups (after incubation with Aβ25-35, add 6.25, 12.5, 25, 50, 100 μmol·L-1 TSG). Cell counting kit-8 (CCK-8) and Lactate dehydrogenase (LDH) methods were used to observe the viability of neuron, immunocytochemical staining was performed to determine the expressions of synapsin-1 (SYN-1), and the concentration of postsynaptic density-95 (PSD-95) and synaptophysin (SYP) were detected by enzyme-linked immunosorbent assay (ELISA) method. The level of cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) and the level of CREB, Phosphorylated CREB (p-CREB) and BDNF proteins were determined by immunocytochemical staining or Western blot (WB). Result: Compared with normal group, the cell survival rate of model group was significantly reduced, LDH release was significantly increased (PPPPPPP-1,25 μmol·L-1 TSG can significantly enhance the expression of SYN-1(PPPPConclusion: TSG possesses the neuroprotective effect on Aβ25-35-induced neuron synapses, the mechanism may be associated with the activation of CREB/BDNF signaling pathway.
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Objective: To explore the improvement of glycyrrhetinic acid (G A) on the damage of synaptic ultrastructures of hippocampus induced by realgar in the mice, and to clarify the related mechanisms. Methods: Sixty ICR mice were randomly divided into three groups with twenty mice in each group: control group (intragastrically treated with 0. 5 % CMC-Na), realgar group (intragatrically treated with realgar 1. 35 g • kg- 1), and GA intervention group (intragastrically administered with GA 48 mg • kgx and realgar 1. 35 g • kg1). The mice were administrated once a day for eight consecutive weeks. The cognitive and memory abilities were tested using object recognition task (ORT). The levels of glutathione (GSH) in the hippocampus in the mice in various groups were detected. The changes of the ultrastructures of synapse in hippocampal CA1 region, the width of synaptic cleft, the length of synaptic active zone, the thickness of post synaptic density (PSD) and the curvature of synaptic interface were observed by transmission electron microscope. Results: Compared with control group, the preferential index (PI) for the novel object and the level of GSH in the hippocampus tissue of the mice in realgar group were significantly decreased (P 0 . 05), and the level of GSH in the hippocampus tissue of the mice in GA intervention group was significantly increased (P 0 . 05). Conclusion: Realgar can change the synaptic structural parameters and cause deficits in cognitive and memory abilities. GA can alleviate the abnormal ultrastructural changes in the hippocampal synapses of the mice.
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OBJECTIVE To observe the changes of synaptic ultrastructures in the rat auditory center after long-term salicylate administration and to elucidate the role of neuroplasticity in some areas of the CNS and its involvement in tinnitus. METHODS The rats were divided into 4 groups: the control group, the acute treatment group, the chronic treatment group, and the recovery group. We investigated ultrastructural alterations in the synapses of inferior colliculus (IC), auditory center (AC) and cerebellum (CRB) by transmission electron microscopy. RESULTS There were more synaptic vesicles (tIC=-4. 61, tAC=-7. 00, P＜0. 01), with greater postsynaptic densities(tIC=-4. 72,P＜0. 01; tAc=-3. 15, P＜0. 05), longer synaptic active zone (tIC=-4. 89, tAC=-3. 48, P＜ 0. 01), and increased synaptic interface curvature (tIC=-2. 32, tAC=-3. 17, P＜0. 05) in the chronic treatment group, as compared with the control group. There were more synaptic vesicles but no other changes in the acute salicylate-treatment group(tIC=-10. 57, tAC=-8. 34, tCRB=-9. 18,P ＜0. 01). CONCLUSION These findings showed that long-term salicylate administration have induced synaptic ultrastructural changes in the IC and AC because of neuroplasticity. These structural changes may result in increased speed and efficacy of chemical synaptic transmission. Alterations to neuroplasticity of the auditory center pathway may lead to tinnitus.
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Background Plasticity of visual system is one of the mechanisms of deprivation amblyopia.Our previous study showed that synapsin plays a role during visual developmental plasticity,and conventional protein kinase C-γ (cPKC-γ) probably is one of upstream kinases of synapsin.However,whether or how the cPKC-γ plays its effects on visual developmental plasticity is below understood.Objective This study was to investigate the dynamic expression of cPKC-γ in visual cortex of normal mice and explore the effects of abnormal visual experience on cPKC-γ expression.Methods The bilateral visual cortex tissues were obtained from 36 clean C57BL/6 mice at postnatal (P) 7,14,21,28,35,42 days respectively and 6 mice for each for the researching of cPKC-γ dynamical expression in visual cortex over aging.Other 24 C57BL/6 mice were randomized into developmental phase group and adult phase group,12 for each group.The monocular deprived (MD) models were established by suturing the upper and inferior eyelides in P14 mice for 14 days in 6 mice in the developmental phase group and 6 healthy mice served as controls,and MD models were established in the same way in 6 P60 mice in the adult phase group,and the same aged mice (6 mice) were used as controls.The mice were sacrificed and bilateral visual cortexes were obtained.The expression of cPKC-γ protein in the visual cortex was quantitatively detected using Western blot assay.The study protocol was approved by Ethic Committee of Tongren Eye Hospital.The use and care of the experimental mice followed the ARVO Statement.Results The cPKC-γ protein was faintly expressed in visual cortex in normal P7 mice,with the related expressing level of (39.74± 11.22)％ and (40.78± 10.37)％ in the left and right cortex,respectively.The expressing level of cPKC-γ protein was gradually increased over aging,with the peak value of (138.68±15.73)％ and (138.47±23.48)％ in P21 mice.A significant difference was found in the expression of cPKC-γ protein in various ages of mice (Fage =57.174,P =0.000),and the expression of cPKC-γ protein was not significantly different between the left and right visual cortexses (Flateral =0.059,P =0.809).No significant differences were found in the expression of cPKC-γ protein on bilateral visual cortexes among the mice of the developmental phase group and adult phase group (Fage =1.798,P =0.159) or among the MD group and normal control group (Fgroup =0.104,P=0.749).Conclusions The dynamic expression of cPKC-γ in the visual cortex of normal mice presents a consistant tend with the aging and development of visual critical period.MD does not affect the expression of cPKC-γ protein in bilateral visual cortexes.Further researches should be performed in the activity of cPKC-γ protein in MD mice.
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Objective To evaluate the effect of ropivacaine-induced convulsion on hippocampal synaptic development in neonatal rats.Methods Sixty 21-day-old Sprague-Dawley neonatal rats,weighing 40-41 g,were randomly divided into 3 groups (n=20 each) using a random number table:control group (group C),single convulsion group (group SC),and recurrent convulsion group (group RC).Normal saline 0.1 ml was intraperitoneally injected in group C.Group SC received single intraperitoneal injection of 0.5％ ropivacaine 33.8 mg/kg.In group RC,0.5％ ropivacaine 33.8 mg/kg was intraperitoneally injected once a day for 5 consecutive days.The rats developed convulsion were included in the study.Five rats were selected at 24 h,3 days and 7 days after convulsion and at the age of 60 days in C and SC groups,and at 24 h,3 days and 7 days after the last convulsion and at the age of 60 days in group RC,the rats were sacrificed,and the hippocampus was removed for examination of the ultrastructure of neurons (with a electron microscope) and for determination of the number of synapses,synaptic space and thickness of synaptic density.Results Compared with group C,the number of synapses was significantly decreased,and the synaptic space was widened at 24 h and 3 days after convulsion,and the thickness of synaptic density was thinned at 24 h after convulsion in group SC,and the number of synapses was significantly decreased,and the synaptic space was widened,and the thickness of synaptic density was thinned at 24 h,3 days and 7 days after convulsion in group RC (P＜0.05).Compared with group SC,the number of synapses was significantly decreased,the synaptic space was widened,and the thickness of synaptic density was thinned at 24 h,3 days and 7 days after convulsion in group RC (P＜0.05).There was no significant difference in the parameters mentioned above at the age of 60 days between the three groups (P＞0.05).Neurons exhibited nuclear swelling,mitochondria showed edema,and disrupted mitochondrial cristae and vacuoles were observed at 24 h and 3 days after convulsion,and these changes mentioned above were significantly attenuated at 24 h,3 days and 7 days after convulsion.Conclusion Ropivacaine-induced convulsion exerts no effects on hippocampal synaptic development in neonatal rats.
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Objective To analyze the expression of synaptophysin (SY) in hippocampal dentate gyrus of rats with hypoxic-ischemic brain damage(HIBD) after the injection of bone marrow stromal cells(BMSCs) and its supernatant into the lateral ventricle and to explore the mechanism of potential effects. Methods Eighty 7-day-old sprague-dawley(SD) rats were randomly divided into sham group, control group, cell group and supernatant group, with 20 rats in each group. The HIBD model was established via the ligation of left carotid arteries followed by 2-hour hypoxia. One week later, control group was injected with 0.01 mol/L PBS via the left ventricle. Meanwhile, cell and supernatant group were injected with BMSCs and supernatant harvested from BMSC culture, respectively, via the same route. For spam group, the left carotid arteries were separated but not ligated, and no hypoxia treatment was imposed on this group. They also received 0.01mol/L PBS injection one week post surgery. After 8 weeks, the expression of SY in the dentate gyrus of rats was measured. Results Compared with sham group, model group showed significantly lower IOD (integral optical density) of SY positive material in the dentate gyrus(P 0.05). Conclusions BMSCs and supernatant injected via the lateral cerebral ventricle can increase SY expression in the hippocampal dentate gyrus of HIBD rats and promote synapse formation. The mechanism of this effect may be related to cytokine secretion by BMSCs which promotes synapse formation.
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All information processing and transmission in the brain involves synapses, the synaptic cell adhesion molecules play an important role in the formation, maturation and maintenance of synapses. Neuroligin1 ( NL1) is excitatory postsynaptic trans?membrane cell adhesion molecules. The interaction between NL1 and other molecules, such as Neurexin1 ( NRXN1) , involves in the formation, plasticity and function of synapses. NL1 knockout or overexpression displayed impairment in learning and memory, thus sug?gesting that NL1 participates in the pathophysiology of neuropsychiatric disease with cognitive dysfunction. Therefore, study of NL1 will open up new avenues to understand pathogenesis of cognitive dysfunction, and may provide a novel insight into prevention and treatment of cognitive dysfunction?associated diseases.
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Lithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4–10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+-permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+-permeable AMPAR modulation). Co-inhibiting PKA, GSK-3β and glutamate reuptake was necessary to bring about changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments revealed that recycling pool size was affected in CLi cultures. Results from minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments indicate that endocytosis in CLi is affected while not much difference is seen in modes of exocytosis. CLi cultures did not show the high KCl associated presynaptic potentiation observed in control cultures. This study, by calling attention to long-term lithium-exposure-induced synaptic changes, might have implications in understanding the side effects such as CNS complications occurring in perinatally exposed babies and cognitive dulling seen in patients on lithium treatment.
ABSTRACT
El quehacer diario de todo Gerente o Directivo se fundamenta en las funciones cognitivas de orden superior que éstos desempeñan. Hoy gracias a la Neurociencia sabemos que dichas funciones cognitivas, son el producto final de una serie de actividades neuronales, pero, ¿quién y cómo se activan? Éstas, junto con otras interrogantes, son las que trata de dilucidar la Neurociencia. En este artículo veremos cómo en esa búsqueda de respuestas, la Neurociencia se ha topado con un hallazgo interesante, el Inconsciente. Veremos cómo científicos de la talla de Libet, Haynes y otros, nos demuestran científicamente que en toda toma de decisión, el inconsciente selecciona una decisión y posteriormente el consciente se entera de ella. Por otro lado, el Dr. Froufe nos habla de la "mente oculta", que al unirla con el Inconsciente de la Neurociencia se formula una alerta, no desestimable, en una de nuestras funciones cotidianas, la toma de decisiones.
The daily work of our Directing Manager is based on the higher order cognitive functions they play. Today, thanks to Neuroscience we know that these cognitive functions are the end product of a series of neural activity, but who and how are activated? these along with other questions are trying to elucidate Neuroscience. In this article we will see how in the search of this answers, Neuroscience has run into an interesting finding, the Unconscious. We will see how scientists of the stature of Libet, Haynes and others, we demonstrate scientifically that in all decision-making, the unconscious select a decision and subsequently, the conscious learns this. On the other hand, Dr. Froufe, speaks of the "hidden mind" that to uniting with the Unconscious of the Neuroscience an alert is made, not negligible, in one of our daily functions, the decision making.