Neuroscience
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The hippocampus plays a critical role in learning, memory, and spatial processing through coordinated network activity including theta and gamma oscillations. Recent evidence suggests that hippocampal subregions (e.g., CA1) can generate these oscillations at the network level, at least in part, through GABAergic interneurons. However, it is unclear whether specific GABAergic interneurons generate intrinsic theta and/or gamma oscillations at the single-cell level. ⋯ In contrast, CB1BCs, SCAs, neurogliaform cells, ivy cells, and the remaining PVBCs (17%) produced intrinsic theta, but not gamma, oscillations. These oscillations were prevented by blockers of persistent sodium current. These data demonstrate that the major types of hippocampal interneurons produce distinct frequency bands of intrinsic perithreshold membrane oscillations.
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Collapsin Response Mediator Protein 2 (CRMP2) is an intracellular protein involved in axon and dendrite growth and specification. In this study, CRMP2 was identified in a conditioned media derived from degenerated sciatic nerves (CM). On cultured rat hippocampal neurons, acute extracellular application of CM or partially purified recombinant CRMP2 produced an increase in cytoplasmic calcium. ⋯ By using live-labeling of CRMP2, Ca2+ channel binding domain 3 (CBD3) peptide derived from CRMP2, and recombinant CRMP2, we demonstrated that that this effect was mediated by an action on the extracellular side of the NMDA receptor. This is the first report of an extracellular action of CRMP2. Prolonged exposure to extracellular CRMP2, may contribute to neuronal calcium dysregulation and neuronal damage.
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Following peripheral nerve injury (PNI), inflammatory cues impede repair. We have previously demonstrated that spinal cord matrix (SCM) proteins and hyaluronic acid (HA) nanofibers mitigate chondroitin sulfate proteoglycan (CSPG) inhibition and promote growth in peripheral neurons. In this study, we evaluated the effects of a characteristic CSPG, chondroitin sulfate A (CSA), SCM, and HA fibers on macrophages and Schwann cells (SCs). ⋯ Antibody arrays were used to measure relative levels of inflammatory cytokines released by the cells. The arrays confirmed that anti-inflammatory cytokines are released from the cells when cultured with our biomaterial cues and helped identify targets for future investigation including vascular endothelial growth factor (VEGF), interleukin (IL)-10, monocyte colony stimulating factor (M-CSF) from the macrophages, Agrin, ciliary neurotrophic factor (CNTF), tissue inhibitor metalloproteinases (TIMPs)-1 from SCs, and IL-2 from both cell types. In conclusion, these results suggest that our biomaterial cues have pro-regenerative effects on both cell types and if combined may trigger cells toward regenerative programs.
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Alzheimer's disease (AD) is the leading cause of dementia worldwide. This pathological condition is characterized not only by Aβ and tau accumulation in the central nervous system (CNS), but also by inflammation, processes that can lead to neurodegeneration. ⋯ Furthermore, cholesterol-associated genes are frequently associated with AD. Here, we extensively reviewed the literature and, based on the existing evidences, we suggest inflammation as an important link between dyslipidemias and AD.
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Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. ⋯ In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC); (ii) ONOO--mediated alteration in mitochondrial permeability transition; (iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex; (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial ONOO--induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys)function can provide new insights into the treatment of neurodegenerative diseases.