scholarly journals Deciphering defective subventricular adult neurogenesis in cyclin D2-deficient mice

2018 ◽  
Author(s):  
Rafał Płatek ◽  
Leszek Kaczmarek ◽  
Artur Czupryn
Keyword(s):  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Hippocampal Neurons ◽  
Specific Cell ◽  
Cyclin D2 ◽  
Long Distance ◽  
Quiescent Cells ◽  
The Central Nervous System ◽  
The Brain ◽  
Deficient Mice

ABSTRACTAdult neurogenesis occurring in the brain of adult mammals is considered to have potential therapeutical applications. New neurons are produced constitutively from postnatal neural stem cells/precursors residing in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer in the dentate gyrus of the hippocampus. Newly-generated neuroblasts from the SVZ migrate long distance towards the olfactory bulb and repopulate different subtypes of inhibitory interneurons modulating the olfactory processing. It was reported that cyclin D2 knockout mice (cD2-KO) present reduced generation of new hippocampal neurons, however proliferation deficiency and mechanisms responsible for dysregulation of subventricular precursors, derived progenitors, and olfactory interneurons need to be detaily investigated. In this report, proliferative activity of different subpopulations of SVZ neural precursors, cell migration, and differentiation in cD2-KO mice was characterized. For that goal, EdU, a thymidine analogue, proliferation mapping combined with multi-epitope immunohisto-chemical detection of endogenous stage-specific cell markers was carried out. Severely reduced number of newly-generated cells in the subventricular niche was demonstrated that was not accompanied by increased level of apoptotic death. Surprisingly, the number of B1 quiescent precursor subpopulation was not affected, whereas the number of B1 type active primary precursors, intermediate/transiently-amplifying progenitors (C type cells), and neuroblasts (A type cells) were reduced. The analyses suggest that cycline D2 might be critical for transition of B1 precursor quiescent cells into B1 active cells. We also demonstrate that the subpopulation of calbindin interneurons is reduced in the olfactory bulb. Deciphering processes underlying a potential modulation of intensity of adult neurogenesis at the cellular levels could lead to replacement therapies after injury, stroke, or neurodegenerative disease in the central nervous system.

scholarly journals Lack of Skeletal Muscle Serotonin Impairs Physical Performance

2021 ◽  
Vol 14 ◽  
pp. 117864692110031
Author(s):  
Marion Falabrègue ◽  
Anne-Claire Boschat ◽  
Romain Jouffroy ◽  
Marieke Derquennes ◽  
Haidar Djemai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Physical Performance ◽  
Depressive Disorders ◽  
Tryptophan Metabolism ◽  
Long Distance ◽  
Positive Effects ◽  
Tryptophan Metabolites ◽  
The Brain ◽  
Deficient Mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

scholarly journals MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

2007 ◽  
Vol 204 (9) ◽  
pp. 2063-2074 ◽  
Author(s):  
Younghwa Kim ◽  
Ping Zhou ◽  
Liping Qian ◽  
Jen-Zen Chuang ◽  
Jessica Lee ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Artificial Chromosome ◽  
Adaptor Proteins ◽  
Innate Immune ◽  
Molecular Structures ◽  
Endogenous Expression ◽  
Microbial Products ◽  
The Brain ◽  
Deficient Mice

The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1–4 in host defense were demonstrated by defective immune responses in knockout mice. In contrast, the sites of expression and functions of vertebrate MyD88-5 have remained elusive. We show that MyD88-5 is distinct from other MyD88s in that MyD88-5 is preferentially expressed in neurons, colocalizes in part with mitochondria and JNK3, and regulates neuronal death. We prepared MyD88-5/GFP transgenic mice via a bacterial artificial chromosome to preserve its endogenous expression pattern. MyD88-5/GFP was detected chiefly in the brain, where it associated with punctate structures within neurons and copurified in part with mitochondria. In vitro, MyD88-5 coimmunoprecipitated with JNK3 and recruited JNK3 from cytosol to mitochondria. Hippocampal neurons from MyD88-5–deficient mice were protected from death after deprivation of oxygen and glucose. In contrast, MyD88-5–null macrophages behaved like wild-type cells in their response to microbial products. Thus, MyD88-5 appears unique among MyD88s in functioning to mediate stress-induced neuronal toxicity.

scholarly journals Identification of the SNARE complex mediating the exocytosis of NMDA receptors

2016 ◽  
Vol 113 (43) ◽  
pp. 12280-12285 ◽  
Author(s):  
Yi Gu ◽  
Richard L. Huganir
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Neurons ◽  
Total Internal Reflection ◽  
De Novo ◽  
Receptor Trafficking ◽  
Snare Complex ◽  
Synaptic Membranes ◽  
Rab Proteins ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system, NMDA receptors mediate excitatory neurotransmissions and play important roles in synaptic plasticity. The regulation of NMDA receptor trafficking is critical for neural functions in the brain. Here, we directly visualized individual exocytic events of NMDA receptors in rat hippocampal neurons by total internal reflection fluorescence microscopy (TIRFM). We found that the constitutive exocytosis of NMDA receptors included both de novo exocytic and recycling events, which were regulated by different Rab proteins. We also identified the SNAP25–VAMP1–syntaxin4 complex mediating the constitutive exocytosis of NMDA receptors. Transient knockdown of each component of the SNARE complex interfered with surface delivery of NMDA receptors to both extrasynaptic and synaptic membranes. Our study uncovers the postsynaptic function of the SNAP25–VAMP1–syntaxin4 complex in mediating the constitutive exocytosis of NMDA receptors, suggesting that this SNARE complex is involved in excitatory synaptic transmission.

scholarly journals Unique Glycan Signatures Regulate Adeno-Associated Virus Tropism in the Developing Brain

2015 ◽  
Vol 89 (7) ◽  
pp. 3976-3987 ◽  
Author(s):  
Giridhar Murlidharan ◽  
Travis Corriher ◽  
H. Troy Ghashghaei ◽  
Aravind Asokan
Keyword(s):  
Polysialic Acid ◽  
Cell Types ◽  
Developing Brain ◽  
Specific Cell ◽  
Developmentally Regulated ◽  
Transport Pathways ◽  
Adeno Associated Virus ◽  
Viral Transport ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTAdeno-associated viruses (AAV) are thought to spread through the central nervous system (CNS) by exploiting cerebrospinal fluid (CSF) flux and hijacking axonal transport pathways. The role of host receptors that mediate these processes is not well understood. In the current study, we utilized AAV serotype 4 (AAV4) as a model to evaluate whether ubiquitously expressed 2,3-linked sialic acid and the developmentally regulated marker 2,8-linked polysialic acid (PSA) regulate viral transport and tropism in the neonatal brain. Modulation of the levels of SA and PSA in cell culture studies using specific neuraminidases revealed possibly opposing roles of the two glycans in AAV4 transduction. Interestingly, upon intracranial injection into lateral ventricles of the neonatal mouse brain, a low-affinity AAV4 mutant (AAV4.18) displayed a striking shift in cellular tropism from 2,3-linked SA+ependymal lining to 2,8-linked PSA+migrating progenitors in the rostral migratory stream and olfactory bulb. In addition, this gain-of-function phenotype correlated with robust CNS spread of AAV4.18 through paravascular transport pathways. Consistent with these observations, altering glycan dynamics within the brain by coadministering SA- and PSA-specific neuraminidases resulted in striking changes to the cellular tropisms and transduction efficiencies of both parental and mutant vectors. We postulate that glycan signatures associated with host development can be exploited to redirect novel AAV vectors to specific cell types in the brain.IMPORTANCEViruses invade the CNS through various mechanisms. In the current study, we utilized AAV as a model to study the dynamics of virus-carbohydrate interactions in the developing brain and their impact on viral tropism. Our findings suggest that carbohydrate content can be exploited to regulate viral transport and tropism in the brain.

scholarly journals The ATF6β-calreticulin axis promotes neuronal survival under endoplasmic reticulum stress and excitotoxicity

2021 ◽  
Author(s):  
Dinh Thi Nguyen ◽  
Thuong Manh Le ◽  
Tsuyoshi Hattori ◽  
Mika Takarada-Iemata ◽  
Hiroshi Ishii ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Hippocampal Neurons ◽  
Neuronal Survival ◽  
Binding Capacity ◽  
Critical Role ◽  
Er Stress Response ◽  
The Central Nervous System ◽  
The Brain

AbstractWhile ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of ATF6β is largely unknown. Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin, a molecular chaperone in the ER with a high Ca2+-binding capacity. Calreticulin expression was reduced to ~50% in the central nervous system of Atf6b−/− mice, and restored by ATF6β. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death, which was rescued by ATF6β, calreticulin, Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in hippocampi of Atf6b−/− and Calr+/− mice, and restored by 2-APB and salubrinal. These results suggest that the ATF6β-calreticulin axis plays a critical role in the neuronal survival by improving Ca2+ homeostasis under ER stress.

Increased µ-opioid receptors in sheep brain after transport

1995 ◽  
Vol 1995 ◽  
pp. 204-204
Author(s):  
E.A. Azaga ◽  
R.G. Rodway
Keyword(s):  
Opioid Receptors ◽  
Opioid Peptide ◽  
Brain Regions ◽  
Long Distance ◽  
Long Distance Transport ◽  
The Central Nervous System ◽  
Sheep Brain ◽  
Transport Stress ◽  
Distance Transport ◽  
The Brain

The long distance transport of sheep before slaughter is at present a very important topic in animal welfare. However, Modulation of opioid receptors can be influenced by chronic treatment with opioid agonists and antagonists (Blanchard, and Chang, 1988). Similarly, opioid receptors can be up or down-regulated by stressful stimuli such as restraint, electric footshock or social isolation and housing (Zeman et al., 1988 and Zanella et al., 1991). The present study was carried out to assess the effects of transport stress on the properties of one class of opioid peptide receptor in the brain of sheep after transport stress. Opioid peptides such as β-endorphin are released by the central nervous system during application of stresses such as transport. They are believed to exert analgesic properties and their effectiveness depends partly on the concentration (Bmax) and affinity (Kd) of their receptors. µ-Opioid receptors are found in various brain regions and are selective for endorphins and similar peptides.

scholarly journals Immovable Object Meets Unstoppable Force? Dialogue Between Resident and Peripheral Myeloid Cells in the Inflamed Brain

2020 ◽  
Vol 11 ◽  
Author(s):  
Alanna G. Spiteri ◽  
Claire L. Wishart ◽  
Nicholas J. C. King
Keyword(s):  
Myeloid Cells ◽  
Cell Types ◽  
Brain Parenchyma ◽  
Specific Cell ◽  
Novel Treatments ◽  
Experimental Systems ◽  
Immune Mediated ◽  
Recent Developments ◽  
The Central Nervous System ◽  
The Brain

Inflammation of the brain parenchyma is characteristic of neurodegenerative, autoimmune, and neuroinflammatory diseases. During this process, microglia, which populate the embryonic brain and become a permanent sentinel myeloid population, are inexorably joined by peripherally derived monocytes, recruited by the central nervous system. These cells can quickly adopt a morphology and immunophenotype similar to microglia. Both microglia and monocytes have been implicated in inducing, enhancing, and/or maintaining immune-mediated pathology and thus disease progression in a number of neuropathologies. For many years, experimental and analytical systems have failed to differentiate resident microglia from peripherally derived myeloid cells accurately. This has impeded our understanding of their precise functions in, and contributions to, these diseases, and hampered the development of novel treatments that could target specific cell subsets. Over the past decade, microglia have been investigated more intensively in the context of neuroimmunological research, fostering the development of more precise experimental systems. In light of our rapidly growing understanding of these cells, we discuss the differential origins of microglia and peripherally derived myeloid cells in the inflamed brain, with an analysis of the problems resolving these cell types phenotypically and morphologically, and highlight recent developments enabling more precise identification.

scholarly journals Gamma Interferon-Induced Inhibition ofToxoplasma gondii in Astrocytes Is Mediated by IGTP

2001 ◽  
Vol 69 (9) ◽  
pp. 5573-5576 ◽  
Author(s):  
Sandra K. Halonen ◽  
Gregory A. Taylor ◽  
Louis M. Weiss
Keyword(s):  
Immunoblot Analysis ◽  
Significant Inhibition ◽  
Gamma Interferon ◽  
Wild Type ◽  
Effector Cells ◽  
Inhibition Of Growth ◽  
The Central Nervous System ◽  
Ifn Γ ◽  
The Brain ◽  
Deficient Mice

ABSTRACT Toxoplasma gondii is an important pathogen in the central nervous system, causing a severe and often fatal encephalitis in patients with AIDS. Gamma interferon (IFN-γ) is the main cytokine preventing reactivation of Toxoplasma encephalitis in the brain. Microglia are important IFN-γ-activated effector cells controlling the growth of T. gondii in the brain via a nitric oxide (NO)-mediated mechanism. IFN-γ can also activate astrocytes to inhibit the growth of T. gondii. Previous studies found that the mechanism in murine astrocytes is independent of NO and all other known anti-Toxoplasma mechanisms. In this study we investigated the role of IGTP, a recently identified IFN-γ-regulated gene, in IFN-γ inhibition of T. gondii in murine astrocytes. Primary astrocytes were cultivated from IGTP-deficient mice, treated with IFN-γ, and then tested for anti-Toxoplasma activity. In wild-type astrocytesT. gondii growth was significantly inhibited by IFN-γ, whereas in astrocytes from IGTP-deficient mice IFN-γ did not cause a significant inhibition of growth. Immunoblot analysis confirmed that IFN-γ induced significant levels of IGTP in wild-type murine astrocytes within 24 h. These results indicate that IGTP plays a central role in the IFN-γ-induced inhibition of T. gondii in murine astrocytes.

scholarly journals Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Almudena Fuster-Matanzo ◽  
María Llorens-Martín ◽  
Félix Hernández ◽  
Jesús Avila
Keyword(s):  
Immune Response ◽  
Alzheimer Disease ◽  
Adult Neurogenesis ◽  
The Elderly ◽  
Therapeutic Approaches ◽  
Common Cause ◽  
The Central Nervous System ◽  
Chronic Activation ◽  
The Brain

Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field.

Regional susceptibilities to mitochondrial dysfunctions in the CNS

2012 ◽  
Vol 393 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Milena Pinto ◽  
Alicia M. Pickrell ◽  
Carlos T. Moraes
Keyword(s):  
Mitochondrial Function ◽  
Neurological Diseases ◽  
Mitochondrial Diseases ◽  
Biochemical Properties ◽  
Specific Cell ◽  
Mitochondrial Dysfunctions ◽  
Common Features ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

Abstract Mitochondrial dysfunctions are very common features of age-related neurological diseases such as Parkinson’s, Alzheimer’s and Huntington’s disease. Several studies have shown that bioenergetic impairments have a major role in the degeneration of the central nervous system (CNS) in these patients. Accordingly, one of the main symptoms in many mitochondrial diseases is severe encephalopathy. The heterogeneity of the brain in terms of anatomic structures, cell composition, regional functions and biochemical properties makes the analysis on this organ very complex and difficult to interpret. Humans, in addition to animal models, exposed to toxins that affect mitochondrial function, in particular oxidative phosphorylation, exhibit degeneration of specific regions within the brain. Moreover, mutations in ubiquitously expressed genes that are involved in mitochondrial function also induce regional-specific cell death in the CNS. In this review, we will discuss some current hypotheses to explain the regional susceptibilities to mitochondrial dysfunctions in the CNS.

Sign in / Sign up

Export Citation Format

Share Document