Neurochemistry international
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Enkephalinergic (ENKergic) neurons have been proposed to play crucial roles in pain modulation in the trigeminal subnucleus caudalis (Vc). To assist an advance in the research of ENKergic neurons, here we used preproenkephalin-green fluorescent protein (PPE-GFP) transgenic mice, in which all ENKergic neurons were fluorescent. We first performed fluorescent in situ hybridization combined with immunofluorescent histochemistry to confirm the specificity of this transgenic mouse and its advantages in showing ENKergic neurons in the Vc. ⋯ We then injected retrograde tracer into the thalamic regions and observed that a small number of ENKergic neurons in the Vc were retrogradely labeled with the tracer. The present results provide a detailed morphological evidence of the neurochemical features of ENKergic neurons. These results have broad implications for understanding the functional roles of ENKergic neurotransmission in the Vc.
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Beta-amyloid (Abeta) peptide, the hallmark of Alzheimer's disease (AD), invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. In this study, salidroside (Sald), an active compound isolated from a traditional Chinese medicinal plant, Rhodiola rosea L., was investigated to assess its protective effects and the underlying mechanisms against Abeta-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Abeta(25-35)-induced neuronal toxicity was characterized by the decrease of cell viability, the release of lactate dehydrogenase (LDH), morphological alterations, neuronal DNA condensation, and the cleavage of poly(ADP-ribose) polymerase (PARP) by activated caspase-3. ⋯ It was also observed that Abeta(25-35) stimulated the phosphorylation of mitogen-activated protein (MAP) kinases, including c-Jun NH(2)-terminal kinase (JNK) and p38 MAP kinase, but not extracellular signal-regulated kinase1/2 (ERK1/2). Salidroside inhibited Abeta(25-35)-induced phosphorylation of JNK and p38 MAP kinase, but not ERK1/2. These results suggest that salidroside has protective effects against Abeta(25-35)-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.
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Synaptic plasticity consists in a change in synaptic strength that is believed to be the basis of learning and memory. Synaptic plasticity has been for a very long period of time a hallmark of neurons. ⋯ Because glial cells are all around synapses and release a wide variety of neuroactive molecule during physiological and pathological conditions, glial cells have been reported to modulate synaptic plasticity in many different ways. From change in synaptic coverage, to release of chemokines and cytokines up to dedicated "glio" transmitters release, glia were reported to affect synaptic scaling, homeostatic plasticity, metaplasticity, long-term potentiation and long-term depression.
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It is widely accepted that mechanical injury to spinal cord can cause nervous system dysfunction, which leads to the loss of movement and sensation. However, the exact molecular mechanism is currently unclear. In this study, contused rat spinal cords were collected at 8h, 1 day, 3, and 5 days after injury and the expression patterns of the proteins were monitored and quantified with two-dimensional gel electrophoresis-based proteomics. ⋯ For example, apoptosis-related protein of heat shock 70 kDa protein 1B increased after contusion, reaching the peak at 1 day; septin 7, a protein involved in cytoskeleton organization, maintained a steady increase for the first 5 days after injury; metabolism-related protein of 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 was constantly down-regulated during the whole time course observed; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide, associated with cell cycle progression, showed a gradual increase after contusion. To our knowledge, this is the first case of detailed and dynamic proteomic snapshots of contusion-induced spinal cord injury. Most of the identified proteins were found for the first time to be differentially expressed after spinal cord contusion, which may help explore the complex molecular cascades underlying the progressive pathologic changes in the contused spinal cord.
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Metabolic alterations in the nervous system can be produced at early stages of toxicity and are linked with oxidative stress, energy depletion and death signaling. Proteases activation is responsible for triggering deadly cascades during cell damage in toxic models. In this study we evaluated the early time-course of toxic events (oxidative damage to lipids, mitochondrial dysfunction and LDH leakage, all at 1, 3 and 6h) in rat striatal slices exposed to quinolinic acid (QUIN, 100 microM) as an excitotoxic/pro-oxidant model, 3-nitropropionic acid (3-NP, 1mM) as an inhibitor of mitochondrial succinate dehydrogenase, and a combined model produced by the co-administration of these two toxins at subtoxic concentrations (21 and 166 microM for QUIN and 3-NP, respectively). ⋯ Our results suggest differential chronologic and mechanistic patterns, depending on the toxic insult. Although LP, MD and membrane cell rupture are shared by the three models, the occurrence of each event seems to obey to a selective recruitment of damaging signals, including a differential activation of proteases in time. Proteases activation is likely to be an up-stream event influencing oxidative stress and mitochondrial dysfunction in these toxic models.