Laboratory of Neurosciences
Laboratory of Neurosciences
Petralia R.S.,35nter Drive |
Wang Y.-X.,35nter Drive |
Mattson M.P.,Laboratory of Neurosciences |
Yao P.J.,Laboratory of Neurosciences
NeuroMolecular Medicine | Year: 2017
Typically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals invaginate—entirely or partially—into postsynaptic processes. We survey these invaginating presynaptic terminals in all animals and describe several examples from the central nervous system, including giant fiber systems in invertebrates, and cup-shaped spines, electroreceptor synapses, and some specialized auditory and vestibular nerve terminals in vertebrates. We then examine mechanoreceptors and photoreceptors, concentrating on the complex of pre- and postsynaptic processes found in basal invaginations of the cell. We discuss in detail the role of vertebrate invaginating horizontal cell processes in both chemical and electrical feedback mechanisms. We also discuss the common presence of indenting or invaginating terminals in neuromuscular junctions on muscles of most kinds of animals, and especially discuss those of Drosophila and vertebrates. Finally, we consider broad questions about the advantages of possessing invaginating presynaptic terminals and describe some effects of aging and disease, especially on neuromuscular junctions. We suggest that the invagination is a mechanism that can enhance both chemical and electrical interactions at the synapse. © 2017 Springer Science+Business Media, LLC (outside the USA)
Liu Y.,Sun Yat Sen University |
Liu Y.,Rutgers University |
Liu Y.,Laboratory of Neurosciences |
Zhou L.-J.,Sun Yat Sen University |
And 21 more authors.
Journal of Neuroscience | Year: 2017
Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of the sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, but impairs LTP in the hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear. Here, we show that the dendrite lengths and spine densities are reduced significantly in hippocampal CA1 pyramidal neurons, but increased in spinal neurokinin-1-positive neurons in mice after SNI, indicating that the excitatory synaptic connectivity is reduced in hippocampus but enhanced in spinal dorsal horn in this neuropathic pain model. Mechanistically, tumor necrosis factor-alpha (TNF-α) is upregulated in bilateral hippocampus and in ipsilateral spinal dorsal horn, whereas brain-derived neurotrophic factor (BDNF) is decreased in the hippocampus but increased in the ipsilateral spinal dorsal horn after SNI. Importantly, the SNI-induced opposite changes in synaptic connectivity and BDNF expression are prevented by genetic deletion of TNF receptor 1 in vivo and are mimicked by TNF-α in cultured slices. Furthermore, SNI activated microglia in both spinal dorsal horn and hippocampus; pharmacological inhibition or genetic ablation of microglia prevented the region-dependent synaptic changes, neuropathic pain, and memory deficits induced by SNI. The data suggest that neuropathic pain involves different structural synaptic alterations in spinal and hippocampal neurons that are mediated by overproduction of TNF-α and microglial activation and may underlie chronic pain and memory deficits. © 2017 the authors.
Kawamoto E.M.,University of Sao Paulo |
Kawamoto E.M.,Laboratory of Neurosciences |
Gleichmann M.,Laboratory of Neurosciences |
Yshii L.M.,University of Sao Paulo |
And 3 more authors.
Brazilian Journal of Medical and Biological Research | Year: 2012
Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid β-peptide (Aβ25-35; 50 μM). Cells (1 × 106 cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer's and Huntington's diseases.
Okun E.,Bar - Ilan University |
Griffioen K.J.,Laboratory of Neurosciences |
Rothman S.,Laboratory of Neurosciences |
Wan R.,Laboratory of Neurosciences |
And 9 more authors.
Brain, Behavior, and Immunity | Year: 2014
Toll-like receptors (TLR) are innate immune receptors typically activated by microbial-associated molecular patterns (MAMPs) during infection or damage-associated molecular patterns (DAMPs) as a result of tissue injury. Recent findings suggest that TLR2 and TLR4 signaling play important roles in developmental and adult neuroplasticity, and in learning and memory. In addition, activation of TLR2 and TLR4 worsens ischemic injury to the heart and brain in animal models of myocardial infarction and stroke. TLR activation is also implicated in thermoregulation and fever in response to infection. However, it is not known whether TLRs participate in the regulation of the sympathetic and/or parasympathetic components of the autonomic nervous system (ANS). Here we provide evidence that TLR2 and TLR4 influence autonomic regulation of heart rate (HR) body temperature and energy metabolism in mice. We show that mice lacking TLR2 or TLR4 exhibit reduced basal HR, which results from an increase of parasympathetic tone. In addition, thermoregulatory responses to stress are altered in TLR2-/- and TLR4-/- mice, and brown fat-dependent thermoregulation is altered in TLR4-/- mice. Moreover, TLR2-/- and TLR4-/- mice consume less food and exhibit a greater mass compared to wild type mice. Collectively, our findings suggest important roles for TLR2 and TLR4 in the ANS regulation of cardiovascular function, thermoregulation, and energy metabolism. © 2013 Elsevier Inc.
Lee J.,Pusan National University |
Jo D.-G.,Sungkyunkwan University |
Park D.,Pusan National University |
Chung H.Y.,Pusan National University |
And 2 more authors.
Pharmacological Reviews | Year: 2014
During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phyto-chemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examples of such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-kB, hypoxia-inducible factor 1a, peroxisome proliferator-activated receptor g, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Trans-lational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied.
Jost C.,Laboratory STICC |
Grandgeorge M.,Laboratory of Neurosciences |
Le Pevedic B.,Laboratory STICC |
Duhaut D.,Laboratory STICC
ACM/IEEE International Conference on Human-Robot Interaction | Year: 2014
This paper presents an experiment which evaluated the added value of a robot in a memory game in three conditions: Tablet and robot, robot alone, and tablet alone. Results show that robots may increase game interest. In our experiment, the presence of a robot did not imply additional workload. It seems that people judged themselves more positively when they interacted with the robot. Moreover, people displayed more positive facial expressions with the robot.
PubMed | Laboratory of Neurosciences and U.S. National Institutes of Health
Type: | Journal: Molecular biology of the cell | Year: 2016
Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. In this study we present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway impacts multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid -peptide, hydrogen peroxide, and high levels of glutamate. Collectively, our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons.
Gutierrez-Leonard H.,Hospital Central Militar |
Martinez-Lara E.,Multidisciplinary Research Laboratory |
Fierro-Macias A.E.,National Polytechnic Institute of Mexico |
Mena-Burciaga V.M.,National Polytechnic Institute of Mexico |
And 3 more authors.
Irish Journal of Medical Science | Year: 2016
Background: Cardiovascular disease is the leading cause of death in the Western world, and a major cause of this disease is atherosclerosis. Research has demonstrated that pregnancy-associated plasma protein A (PAPP-A) plays a role in cardiovascular disease, as evidenced by the association between PAPP-A and severity of heart damage. Aim: The aim of this work was to investigate the correlation between PAPP-A concentrations in coronary and peripheral blood and certain clinicopathological factors and antioxidant enzyme activities in patients diagnosed with coronary artery disease. Methods: For 65 patients, arterial blood was obtained by puncturing the femoral or radial artery, and coronary blood was obtained via percutaneous coronary intervention. PAPP-A, catalase (CAT), superoxide dismutase-1 (SOD-1), and superoxide dismutase-2 (SOD-2) levels were measured using spectrometric methods. Results: Coronary PAPP-A levels were slightly higher than peripheral PAPP-A levels (81.25 ± 2.34 and 62 ± 3 ng/mL, respectively, P < 0.0001); these levels were correlated with each other (r = 0.6629, P < 0.001) but not with clinicopathological factors (P > 0.05). Coronary PAPP-A levels were significantly elevated among patients at risk for cardiovascular disease (P < 0.05). Antioxidant enzyme activities were significantly higher in coronary samples than in peripheral samples from subjects with ischemic cardiopathy secondary to atherosclerosis (P < 0.001). Neither coronary nor peripheral PAPP-A levels were correlated with antioxidant enzyme activities in patients with cardiopathy secondary to atherosclerosis (P > 0.05). Conclusions: PAPP-A levels could be used as biomarkers to identify patients at risk of coronary artery disease. © 2016 Royal Academy of Medicine in Ireland
PubMed | Laboratory of Neurosciences
Type: Journal Article | Journal: Current topics in medicinal chemistry | Year: 2015
High uric acid (UA levels have been correlated with a reduced risk of many neurodegenerative diseases through mechanisms involving chelating Fenton reaction transitional metals, antioxidant quenching of superoxide and hydroxyl free radicals, and as an electron donor that increases antioxidant enzyme activity (e.g. SOD. However, the clinical usefulness of UA is limited by its low water solubility and propensity to form inflammatory crystals at hyperuricemic levels. This review focuses on the role of UA in neuroprotection, as well as potential strategies aimed at increasing UA levels in the soluble range, and the potential therapeutic use of more water-soluble methyl-UA derivatives from the natural catabolic end-products of dietary caffeine, theophylline, and theobromine.