Dendritic Length Research Articles

16. Clathrin-Nanoparticles Efficiently Deliver BDNF to the Hippocampus, Reverse Depression and Neuroinflammation and Increase Neurogenesis, Dendritic Length and Spine Density in HIV/neuroAIDS Mouse Model

16. Clathrin-Nanoparticles Efficiently Deliver BDNF to the Hippocampus, Reverse Depression and Neuroinflammation and Increase Neurogenesis, Dendritic Length and Spine Density in HIV/neuroAIDS Mouse Model

P120-catenin subfamily members have distinct as well as shared effects on dendrite morphology during neuron development in vitro.

Dendritic arborization is essential for proper neuronal connectivity and function. Conversely, abnormal dendrite morphology is associated with several neurological pathologies like Alzheimer's disease and schizophrenia. Among major intrinsic mechanisms that determine the extent of the dendritic arbor is cytoskeletal remodeling. Here, we characterize and compare the impact of the four proteins involved in cytoskeletal remodeling-vertebrate members of the p120-catenin subfamily-on neuronal dendrite morphology. In relation to each of their own distributions, we find that p120-catenin and delta-catenin are expressed at relatively higher proportions in growth cones compared to ARVCF-catenin and p0071-catenin; ARVCF-catenin is expressed at relatively high proportions in the nucleus; and all catenins are expressed in dendritic processes and the soma. Through altering the expression of each p120-subfamily catenin in neurons, we find that exogenous expression of either p120-catenin or delta-catenin correlates with increased dendritic length and branching, whereas their respective depletion decreases dendritic length and branching. While increasing ARVCF-catenin expression also increases dendritic length and branching, decreasing expression has no grossly observable morphological effect. Finally, increasing p0071-catenin expression increases dendritic branching, but not length, while decreasing expression decreases dendritic length and branching. These distinct localization patterns and morphological effects during neuron development suggest that these catenins have both shared and distinct roles in the context of dendrite morphogenesis.

Exploring the effect of Tuina on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation based on NR2B/PSD-95 pathway

ObjectiveTo investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation.MethodsFifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention.ResultsCompared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn.ConclusionTuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.

Low-Intensity Blue Light Exposure Reduces Melanopsin Expression in Intrinsically Photosensitive Retinal Ganglion Cells and Damages Mitochondria in Retinal Ganglion Cells in Wistar Rats.

This study investigated the effect of low-intensity blue light on the albino Wistar rat retina, including intrinsically photosensitive retinal ganglion cells (ipRGCs). Three groups of nine albino Wistar rats were used. One group was continuously exposed to blue light (150 lx) for 2 d (STE); one was exposed to 12 h of blue light and 12 h of darkness for 10 d (LTE); one was maintained in 12 h of white light (150 lx) and 12 h of darkness for 10 d (control). Melanopsin (Opn4) was immunolabelled on retinal whole-mounts. To count and measure Opn4-positive ipRGC somas and dendrites (including Sholl profiles), Neuron J was used. Retinal cryosections were immunolabeled for glial fibrillary acid protein (GFAP) and with terminal deoxynucleotidyl transferase dUTP nick-end labelling for apoptosis detection. LTE reduced the length of Opn4-positive ipRGC dendrites (p = 0.03) and decreased Opn4-immunoreactivity in ipRGC outer stratifying dendrites. LTE and STE decreased the complexity of dendritic arborization (Sholl profile; p < 0.001, p = 0.03, respectively), increased retinal GFAP immunoreactivity (p < 0.001, p = 0.002, respectively), and caused outer segment vesiculation and outer nuclear layer apoptosis. Ultrastructural analysis showed that LTE damaged mitochondria in retinal ganglion cells and in the inner plexiform layer. Thus, LTE to low-intensity blue light harms the retinas of albino Wistar rats.

Peripheral nerve injury elicits microstructural and neurochemical changes in the striatum and substantia nigra of a DYT-TOR1A mouse model with dystonia-like movements

The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still insufficiently understood. DYT-TOR1A dystonia has a remarkably reduced penetrance of 20–30%, which has led to the second-hit hypothesis emphasizing an important role of extragenetic factors in the symptomatogenesis of TOR1A mutation carriers. To analyze whether recovery from a peripheral nerve injury can trigger a dystonic phenotype in asymptomatic hΔGAG3 mice, which overexpress human mutated torsinA, a sciatic nerve crush was applied. An observer-based scoring system as well as an unbiased deep-learning based characterization of the phenotype showed that recovery from a sciatic nerve crush leads to significantly more dystonia-like movements in hΔGAG3 animals compared to wildtype control animals, which persisted over the entire monitored period of 12 weeks. In the basal ganglia, the analysis of medium spiny neurons revealed a significantly reduced number of dendrites, dendrite length and number of spines in the naïve and nerve-crushed hΔGAG3 mice compared to both wildtype control groups indicative of an endophenotypical trait. The volume of striatal calretinin+ interneurons showed alterations in hΔGAG3 mice compared to the wt groups. Nerve-injury related changes were found for striatal ChAT+, parvalbumin+ and nNOS+ interneurons in both genotypes. The dopaminergic neurons of the substantia nigra remained unchanged in number across all groups, however, the cell volume was significantly increased in nerve-crushed hΔGAG3 mice compared to naïve hΔGAG3 mice and wildtype littermates. Moreover, in vivo microdialysis showed an increase of dopamine and its metabolites in the striatum comparing nerve-crushed hΔGAG3 mice to all other groups. The induction of a dystonia-like phenotype in genetically predisposed DYT-TOR1A mice highlights the importance of extragenetic factors in the symptomatogenesis of DYT-TOR1A dystonia. Our experimental approach allowed us to dissect microstructural and neurochemical abnormalities in the basal ganglia, which either reflected a genetic predisposition or endophenotype in DYT-TOR1A mice or a correlate of the induced dystonic phenotype. In particular, neurochemical and morphological changes of the nigrostriatal dopaminergic system were correlated with symptomatogenesis.

MED13L and its disease-associated variants influence the dendritic development of cerebral cortical neurons in the mammalian brain.

The mediator complex comprises multiple subcellular subunits that collectively function as a molecular interface between RNA polymerase II and gene-specific transcription factors. Recently, genetic variants to one subunit of the complex, known as MED13L (mediator complex subunit 13 like), have been implicated in syndromic intellectual disability and distinct facial features, frequently accompanied by congenital heart defects. We investigated the impact of five disease-associated MED13L variants on the subcellular localization and biochemical stability of MED13L protein in vitro and in vivo. In overexpression assays using cortical neurons from embryonic mouse cerebral cortices transduced by in utero electroporation-mediated gene transfer, we found that mouse orthologues of human MED13L-p.P866L and -p.T2162M missense variants accumulated in the nucleus, while the p.S2163L and p.S2177Y variants were diffusely distributed in the cytoplasm. In contrast, we found that the p.Q1922* truncation variant was barely detectable in transduced cells, a phenotype reminiscent of this variant that results in MED13L haploinsufficiency in humans. Next, we analyzed these variants for their effects on neuronal migration, dendritic growth, spine morphology, and axon elongation of cortical neurons in vivo. There, we found that overexpression of the p.P866L variant resulted in reduced number and length of dendrites of cortical layer II/III pyramidal neurons. Furthermore, we show that mMED13L-knockdown abrogated dendritic growth in vivo, and this effect was significantly rescued by co-electroporation of an RNAi-resistant mMED13L, but weakly by the p.T2162M variant, and not at all by the p.S2163L variant. However, overexpression of the p.S2163L variant inhibited mature dendritic spine formation in vivo. Expression of each of the 5 variants did not affect neuronal cell migration and callosal axon elongation in vivo. Taken together, our results demonstrate that MED13L expression is relevant to corticogenesis and influences the dendritic branching characteristics of cortical excitatory neurons. Our study also suggests that disease-associated MED13L variants may directly cause morphological and functional defects in cortical neurons in different ways.

Polydatin Alleviates Chronic Stress-Induced Depressive and Anxiety-like Behaviors in a Mouse Model.

We aimed to investigate whether polydatin could suppress stress-induced depression- and anxiety-like behaviors in a mouse model. Mice were divided into the control group, chronic unpredictable mild stress (CUMS) exposure group, and CUMS mice treated with polydatin group. Following CUMS exposure and polydatin treatment, mice were subjected to behavioral assays to assess depressive-like and anxiety-like behaviors. Synaptic function was determined by the levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), and synaptophysin (SYN) in the hippocampus and cultured hippocampal neurons. The number and length of dendrites were assessed in cultured hippocampal neurons. Finally, we investigated the effect of polydatin on CUMS-induced inflammation and oxidative stress in the hippocampus by measuring inflammatory cytokine levels, oxidative stress markers such as reactive oxygen species, glutathione peroxidase, catalase, and superoxide dismutase, as well as components of the Nrf2 signaling pathway. Polydatin alleviated CUMS-induced depressive-like behaviors in forced swimming, tail suspension and sucrose preference tests, and anxiety-like behaviors in marble-burying and elevated plus maze tests. Polydatin increased the number and length of dendrites of cultured hippocampal neurons from mice exposed to CUMS and alleviated CUMS-induced synaptic deficits by restoring BDNF, PSD95, and SYN levels in vivo and in vitro. Importantly, polydatin inhibited CUMS-induced hippocampal inflammation and oxidative stress and suppressed the activation of NFκB and Nrf2 pathways. Our study suggests that polydatin may be an effective drug for the treatment of affective disorders through inhibiting neuroinflammation and oxidative stress. Our current findings warrant further study to investigate the potential clinical application of polydatin.

Changes at glutamate tripartite synapses in the prefrontal cortex of a new animal model of resilience/vulnerability to acute stress

Stress represents a main risk factor for psychiatric disorders. Whereas it is known that even a single trauma may induce psychiatric disorders in humans, the mechanisms of vulnerability to acute stressors have been little investigated. In this study, we generated a new animal model of resilience/vulnerability to acute footshock (FS) stress in rats and analyzed early functional, molecular, and morphological determinants of stress vulnerability at tripartite glutamate synapses in the prefrontal cortex (PFC). We found that adult male rats subjected to FS can be deemed resilient (FS-R) or vulnerable (FS-V), based on their anhedonic phenotype 24 h after stress exposure, and that these two populations are phenotypically distinguishable up to two weeks afterwards. Basal presynaptic glutamate release was increased in the PFC of FS-V rats, while depolarization-evoked glutamate release and synapsin I phosphorylation at Ser9 were increased in both FS-R and FS-V. In FS-R and FS-V rats the synaptic expression of GluN2A and apical dendritic length of prelimbic PFC layers II–III pyramidal neurons were decreased, while BDNF expression was selectively reduced in FS-V. Depolarization-evoked (carrier-mediated) glutamate release from astroglia perisynaptic processes (gliosomes) was selectively increased in the PFC of FS-V rats, while GLT1 and xCt levels were higher and GS expression reduced in purified PFC gliosomes from FS-R. Overall, we show for the first time that the application of the sucrose intake test to rats exposed to acute FS led to the generation of a novel animal model of resilience/vulnerability to acute stress, which we used to identify early determinants of maladaptive response related to behavioral vulnerability to stress.

Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury

Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on neuronal regeneration after TBI. For in vitro study, stretch-injured neurons were co-cultured with microglial exosomes. For in vivo study, C57BL/6 mice were under controlled cortical impact and injected with microglial exosomes. The results showed that MG-LPS-EXOHT increased the number of dendrite branches and total length of dendrites both in vitro and in vivo, elevated the expression levels of PSD-95 and GluR1 in stretch-injured neurons, and increased spine density in the pericontusion region. Moreover, MG-LPS-EXOHT improved motor function and motor coordination. A high-throughput sequencing showed that miR-20b-5p was upregulated in MG-LPS-EXOHT. Elevating miR-20b-5p promoted neurite outgrowth and synapse recovery of injured neurons both in vitro and in vivo. Following mechanistic study demonstrated that miR-20b-5p might promote neurite outgrowth and synapse recovery by directly targeting PTEN and activating PI3K-AKT pathway. In conclusion, mild hypothermia could modify the microRNA prolife of exosomes derived from LPS activated BV2 cells. Furthermore, high level of microglial exosomal miR-20b-5p induced by mild hypothermia could transfer into injured neurons and promote neurite outgrowth and synapse recovery after TBI via activating the PI3K-AKT pathway by suppressing PTEN expression.

Effect of Sirt3 on hippocampal MnSOD activity, mitochondrial function, physiology, and cognition in an aged murine model

The NAD(+)–dependent deacetylase SIRT3 is a proven mitochondrial metabolic stress sensor. It has been linked to the regulation of the mitochondrial acetylome and activation of several metabolic enzymes (e.g., manganese superoxide dismutase [MnSOD]) to protect mitochondrial function and redox homeostasis, which are vital for survival, excitability, and synaptic signaling of neurons mediating short- and long-term memory formation as well as retention. Eighteen-month-old male and female wild-type (WT) and Sirt3-/- mice were behaviorally tested for hippocampus-dependent cognitive performance in a Morris water maze paradigm. Cognitive impairment was displayed during the probe trial by female and male Sirt3-/- mice but not WT mice. Upon sacrifice, brains were fixed, and morphological assessments were conducted on hippocampal tissues. Both female and male Sirt3-/- mice demonstrated impaired spatial memory retention implying that SIRT3 plays a role in long-term memory function. Golgi-staining studies revealed decreased dendritic arborization and dendritic length in the hippocampi of male Sirt3-/- compared to WT animals. Sirt3 deletion significantly increased NR1, NR2A, and NR2B expression in the hippocampus of female mice only. Enzymatic activity of MnSOD, a major mitochondrial deacetylation target of SIRT3, was significantly decreased in both female and male Sirt3-/- mice. Similarly, both female and male Sirt3-/- mice demonstrated a significant decrease in their respiratory control ratio during Complex I-driven respiration, which was apparent only in female Sirt3-/- mice during Complex II-driven respiration.

MiR-514a promotes neuronal development in human iPSC-derived neurons.

Proper development and function of the central nervous system require precise regulation of gene expression. MicroRNAs (miRNAs), a group of small non-coding RNAs that can negatively regulate gene expression at the post-transcriptional level, are critical regulators of neuronal development, and dysregulation of microRNAs has been implicated in various neurological disorders. Changes in microRNA expression and repertoire are related to the emergence of social and behavioral variations in closely related primates, including humans, during evolution. MicroRNA-514a (miR-514a) is an X-linked miRNA that is conserved in species with higher social and cognitive functions, and frequent tandem duplications of miR-514a have been found in primate genomes. Here, we demonstrate that miR-514a plays a crucial role in neuronal development in neurons derived from human induced pluripotent stem cells (iPSCs). Overexpression of miR-514a increased dendritic length, soma size, and activity levels of mammalian target of rapamycin (mTOR) signaling in induced pluripotent stem cell-derived neurons, whereas blocking of endogenous miR-514a inhibited neuronal development. Furthermore, we performed a functional analysis of the miR-514a variation found during primate evolution, to investigate the impact of miR-514a sequence variation and associated changes in expression on brain development during evolution. We found that mutation in miR-514a significantly reduced the expression of the mature form and abolished the effects observed when native miR-514a was expressed. Our findings provide new insights into the functional role of miR-514a in the regulation of neuronal development and evolution of primate brain development.

Mechanisms Underlying the Recruitment of Inhibitory Interneurons in Fictive Swimming in Developing Xenopus laevis Tadpoles.

Developing spinal circuits generate patterned motor outputs while many neurons with high membrane resistances are still maturing. In the spinal cord of hatchling frog tadpoles of unknown sex, we found that the firing reliability in swimming of inhibitory interneurons with commissural and ipsilateral ascending axons was negatively correlated with their cellular membrane resistance. Further analyses showed that neurons with higher resistances had outward rectifying properties, low firing thresholds, and little delay in firing evoked by current injections. Input synaptic currents these neurons received during swimming, either compound, unitary current amplitudes, or unitary synaptic current numbers, were scaled with their membrane resistances, but their own synaptic outputs were correlated with membrane resistances of their postsynaptic partners. Analyses of neuronal dendritic and axonal lengths and their activities in swimming and cellular input resistances did not reveal a clear correlation pattern. Incorporating these electrical and synaptic properties into a computer swimming model produced robust swimming rhythms, whereas randomizing input synaptic strengths led to the breakdown of swimming rhythms, coupled with less synchronized spiking in the inhibitory interneurons. We conclude that the recruitment of these developing interneurons in swimming can be predicted by cellular input resistances, but the order is opposite to the motor-strength-based recruitment scheme depicted by Henneman's size principle. This form of recruitment/integration order in development before the emergence of refined motor control is progressive potentially with neuronal acquisition of mature electrical and synaptic properties, among which the scaling of input synaptic strengths with cellular input resistance plays a critical role.SIGNIFICANCE STATEMENT The mechanisms on how interneurons are recruited to participate in circuit function in developing neuronal systems are rarely investigated. In 2-d-old frog tadpole spinal cord, we found the recruitment of inhibitory interneurons in swimming is inversely correlated with cellular input resistances, opposite to the motor-strength-based recruitment order depicted by Henneman's size principle. Further analyses showed the amplitude of synaptic inputs that neurons received during swimming was inversely correlated with cellular input resistances. Randomizing/reversing the relation between input synaptic strengths and membrane resistances in modeling broke down swimming rhythms. Therefore, the recruitment or integration of these interneurons is conditional on the acquisition of several electrical and synaptic properties including the scaling of input synaptic strengths with cellular input resistances.

Early Neurobehavioral Characterization of the CD Mouse Model of Williams-Beuren Syndrome.

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.

Facial nerve axotomy induces morphological changes in hippocampal pyramidal neurons.

Facial nerve injury in rats have been widely used to study functional and structural changes that occur in the injured motoneurons and other central nervous system structures related with sensorimotor processing. A decrease in long-term potentiation of hippocampal CA3-to-CA1 commissural synapse has recently been reported related to this peripheral injury. Additionally, it has been found increased corticosterone plasmatic levels, impairment in spatial memory consolidation, and hippocampal microglial activation in animals with facial nerve axotomy. In this work, we analyzed the neuronal morphology of hippocampal CA1 and CA3 pyramidal neurons in animals with either reversible or irreversible facial nerve injury. For this purpose, brain tissues of injured animals sacrificed at different postlesion times, were stained with the Golgi-Cox method and compared with control brains. It was found that both reversible and irreversible facial nerve injury-induced significant decreases in dendritic tree complexity, dendritic length, branch points, and spine density of hippocampal neurons. However, such changes' timing varied according to hippocampal area (CA1 vs. CA3), dendritic area (apical vs. basal), and lesion type (reversible vs. irreversible). In general, the observed changes were transient when animals had the possibility of motor recovery (reversible injury), but perdurable if the recovery from the lesion was impeded (irreversible injury). CA1 apical and CA3 basal dendritic tree morphology were more sensible to irreversible injury. It is concluded that facial nerve injury induced significant changes in hippocampal CA1 and CA3 pyramidal neurons morphology, which could be related to LTP impairments and microglial activation in the hippocampal formation, previously described.

Structure of the Sec14 domain of Kalirin reveals a distinct class of lipid-binding module in RhoGEFs

Gated entry of lipophilic ligands into the enclosed hydrophobic pocket in stand-alone Sec14 domain proteins often links lipid metabolism to membrane trafficking. Similar domains occur in multidomain mammalian proteins that activate small GTPases and regulate actin dynamics. The neuronal RhoGEF Kalirin, a central regulator of cytoskeletal dynamics, contains a Sec14 domain (KalbSec14) followed by multiple spectrin-like repeats and catalytic domains. Previous studies demonstrated that Kalirin lacking its Sec14 domain fails to maintain cell morphology or dendritic spine length, yet whether and how KalbSec14 interacts with lipids remain unknown. Here, we report the structural and biochemical characterization of KalbSec14. KalbSec14 adopts a closed conformation, sealing off the canonical ligand entry site, and instead employs a surface groove to bind a limited set of lysophospholipids. The low-affinity interactions of KalbSec14 with lysolipids are expected to serve as a general model for the regulation of Rho signaling by other Sec14-containing Rho activators.

Mechanical stress-thermodynamic phase-field simulation of lithium dendrite growth in solid electrolyte battery

Growth of lithium dendrites in solid state batteries is an important factor that disturbs their commercial applications. The growth of lithium dendrites at the interface of lithium metal anode will not only lead to the decrease of battery energy efficiency, but also cause combustion, explosion and other safety problems. In order to explore the factors and methods that inhibit the growth of lithium dendrites, the phase-field theory is used to simulate the growth of lithium dendrites in polymer solid electrolyte batteries, and a phase-field model of lithium dendrite growth coupled with mechanical stress and thermal field is established. The effects of key physical factors such as ambient temperature, solid electrolyte Young’s modulus and external stress on dendrite growth and their acting principles are discussed and analyzed. The results show that under the conditions of high temperature, high solid electrolyte Young’s modulus and external stress, the growth of lithium dendrites is slow, the number of long dendrites is small, and the electrodeposition is more uniform. In addition, the effects of Young’s modulus of solid electrolyte and ambient temperature on the growth of lithium dendrites in a common range are compared with each other. It is found that the inhibition effect of changing Young’s modulus of solid electrolyte on the maximum length of lithium dendrites is 19% higher than that caused by the change of ambient temperature.

Exosomes from Hair Follicle Epidermal Neural Crest Stem Cells Promote Acellular Nerve Allografts to Bridge Rat Facial Nerve Defects.

Previous studies showed that acellular nerve allografts (ANAs) have been successfully utilized in repairing peripheral nerve defects, and exosomes produced by stem cells are useful in supporting axon regrowth after peripheral nerve injury. In this study, exosomes from hair follicle epidermal neural crest stem cells (EPI-NCSCs-Exos) combined with ANAs were used to bridge facial nerve defects. EPI-NCSCs-Exos were isolated by ultracentrifuge, and were identified. After coculture, EPI-NCSCs-Exos were internalized into dorsal root ganglions (DRGs) and schwann cells (SCs) in vitro, respectively. EPI-NCSCs-Exos elongate the length of axons and dendrites of DRGs, and accelerated the proliferation and migration of SCs, and increased neurotrophic factor expression of SCs as well. The next step was to assign 24 Sprague Dawley male rats randomly and equally into three groups: the autograft group, the ANA group, and the ANA + EPI-NCSCs-Exos group. Each rat manufactured a 5-mm gap of facial nerve defect and immediately bridged by the corresponding transplants, respectively. After surgery, behavioral changes and electrophysiological testing of each rat were observed and assessed. At 90 days postoperatively, the retrogradely fluorescent tracer-labeled neurons were successfully observed on the injured side in the three groups. Morphological changes of facial nerve regeneration were evaluated by transmission electron microscopy and semithin toluidine blue staining. The results showed that nerve fiber density, nerve fiber diameter, and myelin sheath thickness in the ANA group were significantly worse than those in the other two groups (P < 0.05). No significant difference in nerve fiber density and myelin sheath thickness was observed between the autograft group and the ANA + EPI-NCSCs-Exos group (P = 0.14; P = 0.23). Our data indicated that EPI-NCSCs-Exos facilitate ANAs to bridge facial nerve defects and have the potential to replace autograft therapy in clinic.

The structure and diversity of retinal ganglion cells in the masked greenling Hexagrammos octogrammus Pallas, 1814 (Pisces: Scorpaeniformes: Hexagrammidae).

The authors studied the structure and diversity of retinal ganglion cells (GC) in the masked greenling Hexagrammos octogrammus. In vivo labelling with horseradish peroxidase revealed GCs of various structures in retinal wholemounts. A total of 154 cells were camera lucida drawn, and their digital models were generated. Each cell was characterized by 17 structural and topological parameters. Using nine clustering algorithms, a variety of clusterings were obtained. The optimum clustering was found using silhouette analysis. It was based on a set of three variables associated with dendritic field size and dendrite stratification depth in the retina. A total of nine cell types were discovered. A number of non-parametric tests showed significant pair-wise between-cluster differences in at least four parameters with medium and large effect sizes. Three large-field types differed mainly in dendritic field size, total dendrite length, level of dendrite stratification in the retina and position of somata. Six medium- to small-field types differed mainly in the structural complexity of dendritic arbors and level of dendrite arborization. Cells similar and obviously homologous to types 1-4 were identified in many fish species, including teleosts. Potential homologues of type 5 cells were identified in fewer teleost species. Cells similar to types 6-9 in relative dendritic field size and dendrite arborization pattern were also described in several teleostean species. Nonetheless, their homology is more questionable as their stratification patterns do not match so well as they do in large types. Potential functional matches of the GC types were identified in a number of teleostean species. Type 1 and 2 cells probably match spontaneously active units with the large receptive field centre, so-called dimming and lightening detectors; type 4 may be a counterpart of changing contrast detectors with medium receptive field centre size preferring fast-moving stimuli. Type 3 (biplexiform) cells have no obvious functional matches. Probable functional matches of types 6, 8 and 9 belong to ON-centre elements with small receptive fields such as ON-type direction-selective cells, ON-type spot detectors or ON-type spontaneously active units. Type 5 and 7 cells may match ON-OFF type units, in particular, changing contrast detectors or orientation-selective units. Potential functional matches of GC types presently described are involved in a wide spectrum of visual reactions related to adaptation to gradual change in illumination, predator escape, prey detection and capture, habitat selection and social behaviour.

Rac1 GTPase activation impairs fear conditioning-induced structuralchanges in basolateral amygdala neurons and long-term fear memory formation.

Long-term memory formation leads to enduring alterations in synaptic efficacy and neuronal responses that may be created by changes in neuronal morphology. We show that fear conditioning leads to a long-lasting increase in the volume of the primary and secondary dendritic branches, but not of distal branches, of neurons located at the basolateral amygdala (BLA). The length of the dendritic branches is not affected by fear conditioning. Fear conditioning leads to an enduring increase in the length and volume of dendritic spines, especially in the length of the spine neck and the volume of the spine head. Fear conditioning does not affect dendritic spine density. We further reveal that activation of Rac1 in BLA during fear conditioning impairs long-term auditory, but not contextual, fear conditioning memory. Activation of Rac1 during fear conditioning prevents the enduring increase in the dendritic primary branch volume and dendritic spines length and volume. Rac1 activation per se has no effect on neuronal morphology. These results show that fear conditioning induces changes known to reduce the inhibition of signal propagation along the dendrite and the increase in synaptic efficacy whereas preventing these changes, by Rac1 activation, impairs fear memory formation.

Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice

Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by bc004004 gene, were expressed abundantly in brain tissues with unknown functions. We treated bc004004-/- mice with chronic unpredictable mild stress (CUMS) to test whether those mice were more vulnerable to stress-related disorders. The results of forced swimming test, sucrose preference test, and open field test showed that after being treated with CUMS for 28 days or 35 days both bc004004-/- and bc004004+/+ mice exhibited behavioural changes and there was no significant difference between bc004004+/+ and bc004004-/- . However, behavioural changes were observed only in bc004004-/- mice after being exposed to CUMS for 21 days, but not in bc004004+/+ after 21-day CUMS exposure, indicating that lack of BRAP homologous protein may cause vulnerability to stress-related disorders in mice. In addition, bc004004-/- mice showed a reduction in recognition memory as revealed by novel object recognition test. Since memory changes and stress related behavioural changes are all closely related to the hippocampus function we further analyzed the changes of dendrites and synapses of hippocampal neurons as well as expression levels of some proteins closely related to synaptic function. bc004004-/- mice exhibited decreased dendritic lengths and increased amount of immature spines, as well as altered expression pattern of synaptic related proteins including GluN2A, synaptophysin and BDNF in the hippocampus. Those findings suggest that BRAP homologous protein may have a protective effect on the behavioural response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus.