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CNS Neuroscience & Therapeutics Aug 2023Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs)...
BACKGROUND AND AIM
Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated α-tubulin (α-Ac-Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke.
METHODS
Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen-glucose deprivation models. Thy1-YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of α-tubulin. Thy1 Cre and MEC17 mice were mated to produce mice with decreased expression of α-Ac-Tub in dendritic spines of pyramidal neurons in the cerebral cortex. Moreover, AAV-PHP.B-DIO-MEC17 virus and tubastatin A (TBA) were injected into Thy1 Cre and Thy1-YFP mice to increase α-Ac-Tub expression. Single-pellet retrieval, irregular ladder walking, rotarod, and cylinder tests were performed to test the motor function after the ischemic stroke.
RESULTS
α-Ac-Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke.
CONCLUSION
Our study demonstrated that α-Ac-Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, α-Ac-Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.
Topics: Mice; Animals; Dendritic Spines; Tubulin; Ischemic Stroke; Pyramidal Cells; Stroke
PubMed: 36965035
DOI: 10.1111/cns.14184 -
Aging Cell Sep 2023Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of...
Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of memory formation, in hippocampal slices of old animals. Here, we report that a 2-week treatment with glycogen phosphorylase inhibitor BAY U6751 alleviated memory deficits and stimulated neuroplasticity in old mice. Using the 2-Novel Object Recognition and Novel Object Location tests, we discovered that the prolonged intraperitoneal administration of BAY U6751 improved memory formation in old mice. This was accompanied by changes in morphology of dendritic spines in hippocampal neurons, and by "rejuvenation" of hippocampal proteome. In contrast, in young animals, inhibition of glycogen degradation impaired memory formation; however, as in old mice, it did not alter significantly the morphology and density of cortical dendritic spines. Our findings provide evidence that prolonged inhibition of glycogen phosphorolysis improves memory formation of old animals. This could lead to the development of new strategies for treatment of age-related memory deficits.
Topics: Mice; Animals; Hippocampus; Glycogen Phosphorylase; Memory Disorders; Cognition; Glycogen; Dendritic Spines
PubMed: 37522798
DOI: 10.1111/acel.13928 -
Developmental Cell Jul 2023In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse...
In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.
Topics: Dendrites; Olfactory Bulb; Synapses; Neurons; Cell Differentiation
PubMed: 37290446
DOI: 10.1016/j.devcel.2023.05.004 -
Nanoscale Advances Sep 2023Lithium (Li) metal is considered as an ideal negative electrode material for next-generation secondary batteries; however, the hideous dendrite growth and parasitic...
Lithium (Li) metal is considered as an ideal negative electrode material for next-generation secondary batteries; however, the hideous dendrite growth and parasitic reactions hinder the practical applications of Li metal batteries. Herein, a hybrid polymer film composed of polyvinyl alcohol (PVA) and polyacrylic acid (PAA) is adopted as an artificial protective layer to inhibit the dendritic formation and side reactions in Li metal anodes. PVA with large quantities of polar functional groups can induce even distribution of Li ions (Li). Alternatively, PAA can react with Li metal to form highly elastic and ionic conducting lithium polyacrylic acid (LiPAA), thereby enabling tight contact and flexible self-adaption with Li metal anodes. Therefore, such a rationally designed functional composite layer, with good binding ability and relatively high Li conductivity, as well as excellent capability of homogenizing Li flow, accordingly enables Li metal anodes to reveal dendrite-free plating/stripping behaviours and minimum volume variation. As a result, the PVA-PAA modified Li metal anode delivered stable cycling for 700 and 250 h, respectively, at current densities of 1 and 3 mA cm under an areal capacity of 1 mA h cm, in a carbonate ester-based electrolyte without any additive, exhibiting boosted cycling and rate performances. The Li anode with a functional PVA-PAA hybrid interlayer can maintain the dense and smooth texture without dendrite formation after long cycles. The full cell of Li|LiFeO with our modified Li anode and a cathode with a high areal capacity of 2.45 mA h cm delivers, change to achieved a long-term lifespan of 180 cycles at 1.0 C, with a capacity retention of 96.7%. This work demonstrates a simple and effective strategy of designing multi-functional artificial protective layers, targeting dendrite-free Li anodes.
PubMed: 37705800
DOI: 10.1039/d3na00248a -
Nature Neuroscience May 2024Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to...
Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.
Topics: Animals; Dendrites; Eukaryotic Initiation Factor-4G; Protein Biosynthesis; Neurons; Open Reading Frames; Rats; Mice; Cells, Cultured; Potassium Chloride
PubMed: 38589584
DOI: 10.1038/s41593-024-01615-5 -
Nano Convergence Aug 2023With a high specific capacity and low electrochemical potentials, metal anode batteries that use lithium, sodium and zinc metal anodes, have gained great research... (Review)
Review
With a high specific capacity and low electrochemical potentials, metal anode batteries that use lithium, sodium and zinc metal anodes, have gained great research interest in recent years, as a potential candidate for high-energy-density storage systems. However, the uncontainable dendrite growth during the repeated charging process, deteriorates the battery performance, reduces the battery life and more importantly, raises safety concerns. With their unique properties, two-dimensional (2D) materials, can be used to modify various components in metal batteries, eventually mitigating the dendrite growth, enhancing the cycling stability and rate capability, thus leading to safe and robust metal anodes. In this paper, we review the recent advances of 2D materials and summarize current research progress of using 2D materials in the applications of (i) anode design, (ii) separator engineering, and (iii) electrolyte modifications by guiding metal ion nucleation, increasing ion conductivity, homogenizing the electric field and ion flux, and enhancing the mechanical strength for safe metal anodes. The 2D material modifications provide the ultimate solution for obtaining dendrite-free metal anodes, realizes the high energy storage application, and indicates the importance of 2D materials development. Finally, in-depth understandings of subsequent metal growth are lacking due to research limitations, while more advanced characterizations are welcome for investigating the metal deposition mechanism. The more facile and simplified preparation of 2D materials possess great prospects in high energy density metal anode batteries, and thus fulfils the development of EVs.
PubMed: 37561270
DOI: 10.1186/s40580-023-00384-4 -
Chemical Science Nov 2023Aqueous zinc ion batteries (AZIBs) are regarded as one of the most promising large-scale energy storage systems because of their considerable energy density and... (Review)
Review
Aqueous zinc ion batteries (AZIBs) are regarded as one of the most promising large-scale energy storage systems because of their considerable energy density and intrinsic safety. Nonetheless, the severe dendrite growth of the Zn anode, the serious degradation of the cathode, and the boundedness of separators restrict the application of AZIBs. Fortunately, electrospinning nanofibers demonstrate huge potential and bright prospects in constructing AZIBs with excellent electrochemical performance due to their controllable nanostructure, high conductivity, and large specific surface area (SSA). In this review, we first briefly introduce the principles and processing of the electrospinning technique and the structure design of electrospun fibers in AZIBs. Then, we summarize the recent advances of electrospinning nanofibers in AZIBs, including the cathodes, anodes, and separators, highlighting the nanofibers' working mechanism and the correlations between electrode structure and performance. Finally, based on insightful understanding, the prospects of electrospun fibers for high-performance AZIBs are also presented.
PubMed: 38033908
DOI: 10.1039/d3sc05283d -
Progress in Neurobiology Aug 2024Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their...
Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their dendrites to initiate a pro-regenerative response has not yet been thoroughly investigated. Calcium plays a critical role in the early stages of axonal injury detection and is also indispensable for regeneration of the severed axon. Here, we report cell and neurite type-specific differences in laser injury-induced elevations of intracellular calcium levels. Using a human KCNJ2 transgene, we demonstrate that hyperpolarizing neurons only at the time of injury dampens dendrite regeneration, suggesting that inhibition of injury-induced membrane depolarization (and thus early calcium influx) plays a role in detecting and responding to dendrite injury. In exploring potential downstream calcium-regulated effectors, we identify L-type voltage-gated calcium channels, inositol triphosphate signaling, and protein kinase D activity as drivers of dendrite regeneration. In conclusion, we demonstrate that dendrite injury-induced calcium elevations play a key role in the regenerative response of dendrites and begin to delineate the molecular mechanisms governing dendrite repair.
Topics: Dendrites; Animals; Calcium; Nerve Regeneration; Humans; Mice; Potassium Channels, Inwardly Rectifying; Mice, Transgenic
PubMed: 38825174
DOI: 10.1016/j.pneurobio.2024.102635 -
Frontiers in Bioengineering and... 2023Myosin IXB (MYO9B) is an unconventional myosin with RhoGAP activity and thus is a regulator of actin cytoskeletal organization. MYO9B was previously shown to be...
Myosin IXB (MYO9B) is an unconventional myosin with RhoGAP activity and thus is a regulator of actin cytoskeletal organization. MYO9B was previously shown to be necessary for skeletal growth and health and to play a role in actin-based functions of both osteoblasts and osteoclasts. However, its role in responses to mechanical stimulation of bone cells has not yet been described. Therefore, experiments were undertaken to determine the role of MYO9B in bone cell responses to mechanical stress both and . MYO9B expression was knocked down in osteoblast and osteocyte cell lines using RNA interference and the resulting cells were subjected to mechanical stresses including cyclic tensile strain, fluid shear stress, and plating on different substrates (no substrate vs. monomeric or polymerized collagen type I). Osteocytic cells were also subjected to MYO9B regulation through Slit-Robo signaling. Further, wild-type or mice were subjected to a regimen of whole-body vibration (WBV) and changes in bone quality were assessed by micro-CT. Unlike control cells, MYO9B-deficient osteoblastic cells subjected to uniaxial cyclic tensile strain were unable to orient their actin stress fibers perpendicular to the strain. Osteocytic cells in which MYO9B was knocked down exhibited elongated dendrites but were unable to respond normally to treatments that increase dendrite length such as fluid shear stress and Slit-Robo signaling. Osteocytic responses to mechanical stimuli were also found to be dependent on the polymerization state of collagen type I substrates. Wild-type mice responded to WBV with increased bone tissue mineral density values while mice responded with bone loss. These results demonstrate that MYO9B plays a key role in mechanical stress-induced responses of bone cells and .
PubMed: 37675403
DOI: 10.3389/fbioe.2023.1243303 -
Cell Reports Jul 2023Homeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Postsynaptic guanylate kinase-associated...
Homeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Postsynaptic guanylate kinase-associated protein (GKAP) controls the bidirectional synaptic scaling of AMPA receptors (AMPARs); however, mechanisms by which chronic activity triggers cytoskeletal remodeling to downscale synaptic transmission are barely understood. Here, we report that the microtubule-dependent kinesin motor Kif21b binds GKAP and likewise is located in dendritic spines in a myosin Va- and neuronal-activity-dependent manner. Kif21b depletion unexpectedly alters actin dynamics in spines, and adaptation of actin turnover following chronic activity is lost in Kif21b-knockout neurons. Consistent with a role of the kinesin in regulating actin dynamics, Kif21b overexpression promotes actin polymerization. Moreover, Kif21b controls GKAP removal from spines and the decrease of GluA2-containing AMPARs from the neuronal surface, thereby inducing homeostatic synaptic downscaling. Our data highlight a critical role of Kif21b at the synaptic actin cytoskeleton underlying homeostatic scaling of neuronal firing.
Topics: Actins; Kinesins; Neurons; Neuronal Plasticity; Synapses; Myosins; Dendritic Spines
PubMed: 37418322
DOI: 10.1016/j.celrep.2023.112743