Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats / 中国中药杂志

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Study on the cortical synaptic density and visual function in monocular form deprivation rats with amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effect of monocular form deprivation(MD)on the synaptic density in the visual cortex of the amblyopic rats during the critical period of visual development, the visual cortical synaptophysin(SYN)expression and significance of its expression, as well as the relationship between the synaptic density and the visual function. This research will provide mechanisms underlying the pathogenesis and clinical treatment of amblyopia.<p>METHODS: Normal newborn Long Evans rats were randomly divided into normal control group and amblyopia model group, each with 16 rats. Both groups of rats were raised in the same environment. The normal control group did not receive any treatment. On the 13d after birth, the amblyopic model group received monocular suture to establish a classic monocular form deprived amblyopic model. Both groups of rats were received Visual evoked potential(F-VEP)detection on the 51d. Samples were taken immediately after the detection. The transmission electron microscope and Image J image analysis software were used to observe and analyse the synaptic density in the V1M of the primary visual cortex of the two groups of rats. Frozen sections of visual cortex were stained by immunofluorescence histochemical staining by bleaching method and the expression of SYN positive neurons was observed and quantitatively analyzed. <p>RESULTS: F-VEP examination showed that compared with the normal control group, the P2 latency of the deprived eyes in the amblyopic group was significantly long, and the amplitude of P2 wave was significantly lower than that of normal eyes(<i>P</i><0.05); Transmission electron microscopy results showed that the synaptic density of the bilateral visual cortex of the amblyopic model group was significantly reduced compared with the normal control group(<i>P</i><0.05), the contralateral visual cortex of the amblyopic eye decreased more significantly(<i>P</i><0.05); immunofluorescence staining results showed that the brain slices in the visual cortex of the two groups were intact and the tissue structure was clear under the microscope. Compared with the normal control group, the expression intensity of SYN positive neurons in the amblyopic group was significantly reduced(<i>P</i><0.01).<p>CONCLUSION: There is structural synaptic plasticity during the critical period of visual development. Monocular form deprivation can reduce the synaptic density, SYN expression and the visual function in the primary visual cortex of the amblyopic rats.

Oral simvastatin for 3 continuous months improves learning and memory ability of chronic cerebral hypoperfusion rats / 中国组织工程研究

BACKGROUND: Chronic cerebral hypoperfusion is significantly associated with cognitive decline. Our previous studies have found that mitochondrial aging, increased silent synapses and α-synuclein are important pathological changes of chronic cerebral hypoperfusion. Simvastatin is a traditional lipid regulation agent that can traverse the blood brain barrier, and exerts anti-atherosclerosis, anti-thrombosis and anti-inflammatory effects to improve cognitive function. OBJECTIVE: To observe the effect of continuous oral simvastatin for 3 months on cognitive function of chronic cerebral hypoperfusion male Sprague-Dawley rats, and explore the clinical significance of simvastatin in preventing and treating vascular cognitive impairment and dementia. METHODS: Sprague-Dawley rats were randomly divided into model group, sham group, solvent group and simvastatin group. In the model group, rats were subjected to bilateral common carotid artery occlusion. In the sham group, the bilateral common carotid arteries were not ligated. In the solvent group, the model rats were intragastrically treated with 0.5% carboxymethyl cellulose sodium. In the simvastatin group, the model rats were intragastrically treated with simvastatin suspension. Interventions in each group lasted for 3 months. Behavioral tests were then used to evaluate the learning and memory ability of rats in each group. The expressions of synaptophysin and post-synaptic density 95, key proteins of presynaptic and postsynaptic membrane, were detected by western blot. Ethical approval was obtained from the Animal Experimental Ethics Committee of the General Hospital of Western Theater Command with approval No. 2019ky79. RESULTS AND CONCLUSION: Compared with the sham group, the learning and memory functions of the rats in the model group were significantly impaired. In the open-field test, the moving distance within 5 minutes was significantly reduced in the model group compared with the sham group (P < 0.05), suggesting that autonomous exploration behavior was impaired. In the place navigation test, escape latency was significantly shortened in the model group, implicating the reference memory was damaged. In the spatial probe test, the frequency of passing through the platform and the time for passing through target quadrant were reduced, indicating that the space exploration ability was reduced. In the simvastatin group, however, these indexes were all improved. Western blot results showed that the protein expression of synaptophysin and post-synaptic density 95 decreased significantly in the model group (P < 0.05), but increased in the simvastatin group as compared with the solvent group. Therefore, chronic cerebral hypoperfusion can significantly impair learning and memory function and reduce cognitive level in rats. Continuous oral simvastatin for 3 months can improve cognitive function in chronic cerebral hypoperfusion rats, which indicates that simvastatin may be used as an adjunctive drug to improve the prognosis of patients with vascular cognitive impairment and dementia.

Effect of Electroacupuncture with Different Frequencies on Learning and Memory Ability and Synapse in Hippo-camp in Rats with Alzheimer's Disease / 中国康复理论与实践

Objective To observe the effect of electroacupuncture with different frequencies on learning and memory ability, synaptic morphology and synaptic density in the hippocampus of Alzheimer's disease rats. Methods Forty-eight healthy Wistar rats were randomly di-vided into normal group, sham operation group, model group, 2 Hz, 30 Hz and 50 Hz electroacupuncture groups with 8 cases in each group. The Alzheimer's disease model was established by injecting Aβ1-42 into two sides of lateral cerebral ventricle. The sham operation group was injected with normal saline instead. The electroacupuncture groups received electroacupuncture at Baihui (DU20) and Shenshu (BL23) acu-points. The learning and memory ability was evaluated with Morris water maze test, and the morphology and density of synapse were ob-served by electron microscope. Results Compared with the model group, the latency was shorter, the time of crossing the platform was short-er and the number of crossing the platform was more in the electroacupuncture groups (P<0.01), especially in the 50 Hz electroacupuncture group (P<0.01). The number of synapse and the synaptic density were more in the electroacupuncture groups than in the model group (P<0.01), especially in the 50 Hz electroacupuncture group (P<0.01). Conclusion Electroacupuncture could improve learning and memory abili-ty and increase synaptic density in rats with Alzheimer's disease, especially with high frequency.

Membrane-associated guanylate kinases and cerebral ischemia / 国际脑血管病杂志

Membrane-associated guanylate kinases (MAGUKs) is a class of postsynaptic density proteins (PSDs) in the postsynaptic dense of the postsynaptic membrane,including PSD-95,SAP-102,PSD-93,and SAP-97.MAGUK family members contain several protein binding sites,and these special binding sites are responsible for mediating a variety of signal transduction.MAGUKs participate in the occurrence and development mechanisms in central nervous system diseases,and has become a topic of general interest of neuroscience.This article briefly reviews the roles of MAGUKs in ischemic brain injury.

Temporal Changes of Post Synaptic Signaling Molecules, Post Synaptic Density-95 and Neuronal Nitric Oxide Synthase, in the Inner Molecular Layer of the Mouse Dentate Gyrus during Voluntary Running / 대한해부학회지

Here, we investigated the temporal change of post synapse signaling molecules, post synaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) using immunohistochemistry during voluntary running with upregulated neurogenesis. Rate of running was stabilized after two weeks of the six week trial. By using immunohistochemsitry for phosphorylated cAMP response element binding protein (pCREB) and polysialylatedneural cell adhesion molecules (PSA-NCAM), we observed that the differentiation in dentate granule cells of adult mouse hippocampus increased at 1 and 2 weeks of voluntary running. We found that, at 6 weeks of voluntary running, the differentiation in dentate granule cells of adult mouse hippocampus returned to sedentary control levels. On the other hand, PSD-95 and nNOS immunoreactivity decreased in the inner molecular layer in the dentate gyrus of hippocampus after 1 and 2 weeks of voluntary running. At 6 weeks of voluntary running, the density of the PSD-95 and nNOS in the inner molecular layer was returned to the sedentary control level. The reactivity of nicotinamide dinucleotide phosphate diaphorase (NADPH-diaphorase), the marker of nitric oxide synthase activity, confirmed the change of nNOS in the inner molecular layer during voluntary running. These results demonstrate that the differentiation and the synaptic activity of granule cells during voluntary running are changed reciprocally once the rate of running has stabilized. These granule cell changes during voluntary running suggest an adaptation response to the new environment.

The Effects of Repeated Restraint Stress on the Synaptic Plasticity in the Inner Molecular Layer of Mouse Dentate Gyrus / 체질인류학회지

Stress induces degeneration of brain structures and functions. Particularly, hippocampus is sensitive to stressful stimulations. In the present study, the change of synaptic related molecules in the mouse dentate gyrus was examined with immunohistochemistry after restraint stress. We subjected mice to restraint stress for 6 h per day for 4 days. As a result, the number of Ki-67, a marker for proliferation, and doublecortin (DCX), a marker for neurogenesis, immunoreactive cells was decreased in the stress group. On the other hand, the intensity of calbindinD-28k, a marker of pre-existing granule cells, immunoreactivity was increased in the granule cell layer after 4 days restraint stress. As well as, the immunoreactivity of synaptic related molecules, postsynaptic density-95 (PSD-95), growth association protein-43 (GAP-43) and beta-NADPH-d reactivity were increased in the inner molecular layer of dentate gyrus after 4 days restraint stress. In conclusion, this study shows that repeated restraint stress suppresses neurogenesis in dentate gyrus and strengthens synaptic plasticity of existing granule cells.