Search

Exploring the relationship between neuronal loss in adult visual cortex and its consequential changes in synaptic connection provides experimental evidence to elucidate impaired visual function upon traumatic brain injury. The primary visual cortex (V1) of 8-week-old C57BL/6 mice was sparsely infected with adeno-associated viruses (AAVs) encoding diphtheria toxin A (DTA) to induce neuronal apoptosis. Neuronal number and dendritic spine morphology of surviving pyramidal neurons in layers 2-4 of visual cortex were analyzed using immunofluorescence staining, Golgi staining and confocal microscopy after four weeks post-injection. Through stereotactic injection of different titers (E+11-13) of DTA-expressing viruses, mouse models were generated with various levels of neuronal loss (by 14~85%) in the adult visual cortex. The results revealed that low-titer (E+11) DTA-expressing AAV led to moderate reduction of neuronal number (by~18%, P＜0.01), mimicking the level of neuronal loss in patients with mild traumatic brain injury (16.5~2.9%). In this DTA group, while dendritic spine density of pyramidal neurons did not change in comparison to the control group, the proportion of mature spines reduced by ~19% (P＜0.0001). Neuronal loss in adult visual cortex impaired synaptic connection and probably compromised visual function in the brain. [ABSTRACT FROM AUTHOR]

Objective: To discuss the ameliorative effect of a novel antiepileptic drug Q808 on neuronal injury in temporal lobe epilepsy (TLE) rats, and to clarify its mechanism of action. Methods: TLE rat model was prepared by intraperitoneal injection of the innovative antiepileptic drug candidate 6- (4-chlorophenoxy) - tetrazolo (5, 1-a) phthalazine (Q808). Forty-five successfully modeled rats were randomly divided into model group, low dose of Q808 group, and high dose of Q808 group, and there were 15 rats in each group. The rats in low dose of Q808 group and high dose of Q808 group were gavaged with 20 and 80 mg·kg-1 Q808, respectively, and the rats in model group were gavaged with an equal amount of 0. 3% sodium carboxymethyl cellulose. Another 15 healthy SD rats were selected as control group. After 4 weeks of continuous gavage treatment, the morphology of the rats in varioius groups was observed; PONEMAH 6. X experimental animal telemetry platform was used to record the electroencephalogram of the rats in various groups; Golgi staining was used to observe the morphology of dendritic and dendritic spine density of hippocampal CA1 neurons of the rats in various groups; Western blotting method was used to detect the expression levels of synaptic plasticity-specific protein calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) in hippocampus tissue of the rats in various groups. Results: The rats in control group showed normal activity without convulsions or other abnormal manifestations. The rats in model group, low dose of Q808 group, and high dose of Q808 group showed varying degrees of reduced activity, trembling and nodding, loss of balance, muscle rigidity and forelimb convulsions, gradually transforming into whole-body muscle rigidity and standing, followed by falling backwards, and there were no convulsions during the interictal period. Compared with control group, the total durations of epileptic seizures of the rats in model group, low dose of Q808 group, and high dose of Q808 group were significantly prolonged (P<0. 01). Compared with model group, the total durations of epileptic seizures in low dose of Q808 group and high dose of Q808 group were significantly shortened (P<0. 01). The hippocampal CA1 neurons of the rats in control group showed regular distribution of dendrites with dense and orderly dendritic networks. The hippocampal CA1 neurons of the rats in model group showed disordered arrangement of dendrites with massive dendritic entanglement, forming thicker nerve fiber bundles. Compared with model group, the dendritic networks of hippocampal CA1 neurons of the rats in low dose of Q808 group and high dose of Q808 group were partially recovered with relatively regular arrangement. Compared with control group, the dendritic spine density of hippocampal CA1 neurons of the rats in model group was significantly decreased (P<0. 01). Compared with model group, the dendritic spine densities of hippocampal CA1 neurons in low dose of Q808 group and high dose of Q808 group significantly increased (P<0. 01). Compared with control group, the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in model group, low dose of Q808 group, and high dose of Q808 group were significantly decreased (P< 0. 01). Compared with model group, the expression levels of CaMKⅡ protein in hippocampus tissue of the rats in low dose of Q808 group and high dose of Q808 group were significantly increased (P<0. 01). Conclusion: The novel antiepileptic drug Q808 has an ameliorating effect on the TLE model rats; its mechanism may be related to Q808's ability to reduce the dendritic lesions in hippocampal CA1 neurons and increase the expression level of synaptic plasticity-related protein CaMKⅡ protein. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of exercise training (swimming combined with wheel running) on dendritic spine remodeling in the medial prefrontal cortex of rats with autism spectrum disorder (ASD) induced by valproic acid (VPA), and to explore the roles of microtubule affinity regulating kinase 1 (MARK1), microtubule-associated protein 1A (MAP1A) and postsynaptic density protein-95 (PSD-95). METHODS: The ASD model rats and normal control rats were generated by collecting the male offspring of rats exposed to VPA or normal saline during pregnancy. The rats were randomly divided into an exercise group and a sedentary group, with 9 to 11 rats in each group. The effect of exercise on the sociability of the rats with ASD was evaluated by a social behavior test. The density and morphology of dendritic spines in the prelimbic cortex (PrL) and infralimbic cortex (IL) were observed following stereotaxic injection of a fluorescent virus. Western blot was used to assess the protein expression of PSD-95 and synaptophysin (Syn), and RNA in situ hybridization was used to determine the RNA expression and colocalization of MARK1, MAP1A and PSD-95. RESULTS : The time spent in the chamber containing an unfamiliar rat and the time and frequency of sniffing the unfamiliar rat were significantly lower in the ASD model group than that in the control group, demonstrating that the sociability of the ASD model rats was impaired (P<0. 05). After exercise intervention, the social behavior of the ASD model rats significantly improved (P<0. 05). The total spine density, mushroom spine density, and stubby spine density were significantly increased in the PrL but not in the IL of the ASD model rats, and these changes were effectively reversed after exercise intervention. Western blot analysis showed that exercise intervention effectively abrogated the increase in the protein expression of PSD-95 in the PrL of the ASD model rats (P<0. 05). However, the expression of Syn in the PrL and the expression of PSD-95 and Syn in the IL were not significantly different. RNA in situ hybridization experiments showed that exercise intervention effectively reduced the number of RNA-positive particles of MARK1, MAP1A and PSD-95 in the PrL of the ASD model rats and reduced the colocalization of MARK1 and MAP1A, MARK1 and PSD-95 and MAP1A and PSD-95. CONCLUSION: Exercise intervention may improve the remodeling of dendritic spines through MARK1/MAP1A/PSD-95 signaling in the PrL, thereby improving the social behavior of ASD model rats. [ABSTRACT FROM AUTHOR]

Objective: To explore how Yiqi Huatan Decoction can modulate synaptic dysfunction in a mouse model of chronic unpredictable mild stress (CUMS) depression by suppressing NLRP3 inflammasome in microglia and A1-like astrocytes activation. Methods: C57BL/6J mice were categorized into four groups: normal, model, MCC950, and Yiqi Huatan Decoction. With the exception of the normal group, all other groups underwent CUMS to induce depression, and subsequently received either MCC950 or Yiqi Huatan Decoction as treatment. The depression-like behavior of mice was evaluated using the Sucrose preference test (SPT), Novelty suppressed feeding test (NSF), Tail suspension test (TST), and Forced swimming test (FST). The synaptic structure of the hippocampus was examined through Golgi staining. Immunofluorescence staining was utilized to detect the colocalization of GFAP and C3, as well as Iba1 and NLRP3 in the hippocampus of mice. Additionally, the mRNA levels of TNF-α, IL-1α, and C1qA were measured using quantitative Real-time PCR. The protein expression of SYP, PSD-95, C3, NLRP3, ASC, Caspase-1, and IL-1β in the mouse hippocampus were determined through Western Blot analysis. Results: Compared to the control group, the mice in the experimental group exhibited a notable decrease in sucrose preference, an extended period of time before initiating feeding in NSF, and an increased duration of immobility in both TST and FST(P<0.05). In addition, mice exhibiting depressive symptoms demonstrated a reduction in the quantity of dendritic branches and dendritic spine density within the hippocampus(P<0.01). Furthermore, there was a notable rise in the number of co-localized positive cells expressing GFAP and C3 or Iba1 and NLRP3(P<0.01), along with elevated levels of TNF-α, IL-1α, and C1qA mRNA expression(P< 0.01). Conversely, a decrease in the expression of SYP and PSD-95 proteins was observed(P<0.05), while a significant increase in the expression of C3, NLRP3, ASC, Caspase-1, and IL-1β proteins was noted(P<0.01). In contrast to the model group, the mice in the Yiqi Huatan Decoction group exhibited a higher sucrose preference rate and reduced latency in NSF. Additionally, the immobility time in both TST and FST was significantly decreased(P<0.01). Furthermore, the administration of Yiqi Huatan Decoction to mice resulted in a significant increase in the number of hippocampal dendritic branches and dendritic spine density (P< 0.01). Additionally, there was a significant decrease in the number of co-localised positive cells of GFAP and C3, Iba1 and NLRP3 (P<0.01). Moreover, the mRNA levels of TNF-α, IL-1α, and C1qA were significantly reduced (P<0.01), while the protein expression of SYP and PSD-95 increased(P<0.05). Conversely, the protein expression of C3, NLRP3, ASC, Caspase-1, and IL-1β were all significantly reduced(P<0.05). Conclusion: The administration of Yiqi Huatan Decoction has been found to mitigate synaptic function impairment and ameliorate depressive-like behavior in mice subjected to CUMS. This therapeutic effect is achieved through the inhibition of NLRP3 inflammasome activation in hippocampal microglia and the reduction in the activation of neurotoxic A1-like astrocytes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the effects ginkgo diterpene ginkgolides ( DG) on cognitive function of immature rats anesthetized by ketamine. METHODS: Fifty immature SD rats were randomly divided into the control group (Con), ketamine group (Ket), DG low-dose group (DG-L, 2. 5 mg / kg), DG medium-dose group (DG-M, 5 mg / kg) and DG high-dose group ( DG-H, 10 mg / kg). The rats in non-control group were anesthetized with 100 mg / kg ketamine for cognitive dysfunction model. Different doses of DG were intraperitoneally injected. Morris water maze was used to detect cognitive function, long-term potential was used to detect synaptic plasticity, Golgi stain was used to detect the state of dendritic spines, Western Blot was used to detect the expression of brain-derived neurotrophic factor ( BDNF), TrkB and PSD-95 protein. RESULTS: Compared with the Con group, ketamine anesthesia (Ket group, DG-L, DG-M and DG-H) resulted in increased escape latency, decreased number of crossing platforms, decreased density and length of mediated dendritic spines, down-regulated excitatory postsynaptic field potential ( fEPSP ) level, and decreased expression of BDNF, TrkB and PSD-95 proteins in the hippocampus, decreased B-cell lymphoma 2 (Bcl-2) expression, increased cleaved-caspase-3 and Bcl-2 associated X protein (Bax) expression. Compared with the Ket group, the escape latency of immature rats in the DG-M and DG-H was significantly shortened, the number of crossing platforms increased, the growth of dendritic spines was promoted, the level of fEPSP was up-regulated, the protein expressions of BDNF, TrkB and PSD-95 increased, and Bcl-2 expression increased, and the cleaved-caspase-3 and Bax expression decreased. CONCLUSIONS: By increasing the protein expression of BDNF, TrkB and PSD-95, DG reduces the ketamine-induced dendritic spine injury in immature rats, up-regulates the fEPSP, and improves the cognitive impairment in immature rats. [ABSTRACT FROM AUTHOR]

Objective To investigate expression changes of phospholipase C-γ1 (PLCγ1)/inositol triphosphate receptor (IP3R)/calmodulin-dependent kinase Ⅱ (CaMKⅡ) and density of dendritic spine in the hippocampus of autism model mice induced by sodium valproate (VPA). Methods Pregnant C57 mouse was given intraperitoneal injection of 300 mg/kg VPA or same volume of normal saline at the 10th and 12th days of gestation. The offspring exposed to VPA or saline during gestation were identified as autism spectrum disorder mice (VPA group) or normal control mice (CON group). Western blotting was used to detect the expression levels of PLCγ1, IP3R, CaMKⅡ and post-synaptic dense-95 (PSD95) in the hippocampus of the 2 groups. Golgi staining was employed to observe the changes in dendritic spines in the hippocampus of the offspring mice. Results Western blotting showed that the expression levels of PLCγ1, IP3R, CaMKⅡ and PSD95 were decreased in the VPA group than the normal control group (P < 0.01). Golgi staining indicated that compared with the normal control group, the density of dendritic spines in the hippocampus of VPA mice was reduced (P < 0.01). Conclusion In the hippocampus of VPA induced autism mice, the expression of PLCγ1/IP3R/CaMKⅡ and PSD95 and the dendritic spine density of pyramidal neurons in hippocampal CA1 are all decreased compared with the normal control mice.

Objective: To explore the role of melatonin in the mechanism of remifentanil-induced hyperalgesia in rats by improving the plasticity of neuronal dendritic spines. Methods: Purchase 30 SD rats (175~200 g) aged 8-10 weeks. According to the purpose of the study, all rats were randomly divided into three groups: control group (rats undergoing incision surgery on the soles of rats, treated with saline, n=10), model group (rats undergoing incisions on the soles of rats, sutured intravenously remifentanil, n=10), treatment group (melatonin treatment on the basis of the model group, n=10). Shrinkage feet reflection of rats in different groups at 2 h, 2 d, 3 d and 7 d after treatment was detected by the paw withdrawal threshold and the paw withdrawal latency time. The mRNA expression of IL-1, TNF-α and IL-1β in rats was analyzed by RT-qPCR. The protein expression of AMPA and Kalirin-7 in rats was detected by Western blot. The heat sensitivity of rats was evaluated by a hot-plate biological instrument. The density and length of the spine of rats in different groups were compared by observing tissue sections. The electrophysiology of a single neuron is analyzed by the camera monitor of a low-sensitivity charge-coupled device. Results: In the 2 h, 2 d, 3 d and 7 d tests, comparing with the control group, the paw withdrawal threshold was lower (P<0.05), the paw withdrawal latency time was shorter (P<0.05), the mRNA expression of IL-1, TNF-α, IL-1β and the protein expression of AMPA and Kalin-7 was higher (P<0.05) in the model group. And the spine density and length and the current amplitude was higher (P<0.05), the current interval was lower (P<0.05) in the model group. Comparing with the model group, the paw withdrawal threshold was higher(P<0.05), the paw withdrawal latency time was longer(P<0.05), the mRNA expression of IL-1, TNF-α, IL-1βand the protein expression of AMPA and Kalin-7 was lower (P<0.05) in the treatment group. And the spine density and length and the current amplitude was lower (P<0.05), the current interval was increased (P<0.05) in the model group. Conclusion: Melatonin improves the plasticity of neuronal dendritic spines by inhibiting the protein expression of AMPA and Kalirin-7, thereby reducing remifentanil- induced hyperalgesia in rats. [ABSTRACT FROM AUTHOR]

Copyright of China Sciencepaper is the property of China Sciencepaper and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The dendritic spines are the sites of a direct link between neurons, and their morphological plasticity is the structural basis of memory. Glutamate receptor pathway is considered to be the main way of information transmission in central nervous system. It plays an important role in the plasticity of synaptic transmission efficiency, which results in the morphological changes of dendritic spines. In this paper, from the perspective of glutamate receptor, the regulatory mechanism of morphological plasticity of dendritic spines is reviewed. Glutamate receptor could regulate actin dynamic proteins in the spine mainly induced by its downstream signaling molecules, therefore, morphogenesis and stability of dendritic spines occur. This role is regulated by different proteins, signaling molecules, hormones, mi RNAs etc in local brain areas, which participate in physiological and pathological process. In the end, the prospective in this field is also discussed. And Studies about the changes of local microenvironment in specific brain region will provide a reference value on investigation of causes and treatments of memory related diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the mechanism of valproic acid (VPA) -induced impairment of the dendritic spines and synapses in the prefrontal cortex (PFC) for causing core symptoms of autism spectrum disorder (ASD) in mice., Methods: Female C57 mice were subjected to injections of saline or VPA on gestational days 10 and 12, and the male offspring mice in the two groups were used as the normal control group and ASD model group ( n =10), respectively. Another 20 male mice with fetal exposure to VPA were randomized into two groups for stereotactic injection of DMSO or Wortmannin into the PFC ( n =10). Open field test, juvenile play test and 3-chamber test were used to evaluate autistic behaviors of the mice. The density of dendrite spines in the PFC was observed with Golgi staining. Western blotting and immunofluorescence staining were used to detect the expressions of p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and the synaptic proteins PSD95, p-Syn, and Syn in the PFC of the mice., Results: Compared with the normal control mice, the mice with fetal exposure to VPA exhibited obvious autism-like behaviors with significantly decreased density of total, mushroom and stubby dendritic spines ( P < 0.05) and increased filopodia dendritic spines ( P < 0.05) in the PFC. The VPA-exposed mice also showed significantly increased expressions of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR ( P < 0.01) and lowered expressions of PSD95 and p-Syn/Syn in the PFC ( P < 0.05 or 0.001). Wortmannin injection into the PFC obviously improved the ASD-like phenotype and dendritic spine development, down-regulated PI3K/Akt/mTOR signaling pathway and up-regulated the synaptic proteins in VPA-exposed mice., Conclusion: In male mice with fetal exposure to VPA, excessive activation of PI3K/Akt/mTOR signaling pathway and decreased expressions of the synaptic proteins PSD95 and p-Syn cause dendritic spine damage and synaptic development disturbance in the PFC, which eventually leads to ASD-like phenotype.

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.

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

This study was performed to investigate the changes of the number, morphology and ultrastructure of the central nervous system of mice during the long-term alcohol exposure. Mice at 60 days in age were used to establish the long-term alcohol exposure model. The structure of the central nervous system, such as nuclear antigen, dendritic spines and synapses, were labeled by the methods of immunocytochemistry and DiI (1,1’- dioctadecyl-3,3,3’,3’-tetramethy lindocarbocyanine perchlorate) scattering. The results showed that prolonged alcohol exposure could promote apoptosis of nerve cells in the central nervous system, and inhibit the proliferation of neural stem cells, which reduced the number of nerve cells in the central nervous system. Long-term ethanol exposure can also lead to a decrease in the density of dendritic spines of neuron, a smaller number of synapses(connections between nerve cells), and some changes in synaptic ultrastructure. The density of nerve cells and their dendritic spines, as well as the changes of synaptic ultrastructure, suggest that the function of nerve cells may be low.