DOCSLIB.ORG

Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus The Journal of Neuroscience, April 15, 2000, 20(8):2896–2903 Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus Maria A. I. Åberg,1 N. David Åberg,1 Helena Hedba¨ cker,1 Jan Oscarsson,2 and Peter S. Eriksson1 1Institute of Clinical Neuroscience, Sahlgrenska University Hospital, and 2Department of Physiology and Pharmacology, Go¨ teborg University, Go¨ teborg, Sweden In several species, including humans, the dentate granule cell progeny, we characterized the colocalization of BrdU- layer (GCL) of the hippocampus exhibits neurogenesis through- immunolabeled cells with cell-specific markers. In animals out adult life. The ability to regulate adult neurogenesis phar- treated with IGF-I for 20 d, BrdU-positive cells increased sig- macologically may be of therapeutic value as a mechanism for nificantly. Furthermore, the fraction of newly generated neurons replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a in the GCL increased, as evaluated by the neuronal markers growth-promoting peptide hormone that has been shown to Calbindin D28K , microtubule-associated protein-2, and NeuN. have neurotrophic properties. The relationship between IGF-I There was no difference in the fraction of newly generated and adult hippocampal neurogenesis is to date unknown. The astrocytes. Thus, our results show that peripheral infusion of aim of this study was to investigate the effect of the peripheral IGF-I increases progenitor cell proliferation and selectively in- administration of IGF-I on cellular proliferation in the dentate duces neurogenesis in the progeny of adult neural progenitor subgranular proliferative zone, which contains neuronal pro- cells. This corresponds to a 78 Ϯ 17% ( p Ͻ 0.001) increase in genitor cells, and on the subsequent migration and differentia- the number of new neurons in IGF-I-treated animals compared tion of progenitor cells within the GCL. Using bromodeoxyuri- with controls. dine (BrdU) labeling, we found a significant increase of BrdU- immunoreactive progenitors in the GCL after6dofperipheral Key words: brain; rat; IGF-I; insulin-like growth factor-I; stem IGF-I administration. To determine the cell fate in progenitor cell; progenitor cell; hippocampus; neurogenesis; stereology Most CNS neurons are terminally differentiated and are, thus, not ing neurons (Suhonen et al., 1996). Proliferation and differentia- replaced after neuronal cell death. However, self-renewing cells tion of adult neural stem cells are affected by age, growth factors, with multilineage potential, designated stem cells or progenitor excitatory input, adrenal steroids, seizures, and enrichment of the cells, have been identified in the adult mammalian brain (Reyn- environment (Cameron and Gould, 1994; Palmer et al., 1995; olds and Weiss, 1992; Richards et al., 1992; Craig et al., 1996; Craig et al., 1996; Kuhn et al., 1996; Bengzon et al., 1997; Gould Suhonen et al., 1996; McKay, 1997; Temple and Alvarez-Buylla, et al., 1997; Kempermann et al., 1997; McKay, 1997; Nilsson et al., 1999). Neural stem cells generate new neurons throughout life in 1999). However, there are to our knowledge no known exogenous the dentate gyrus of the hippocampus in several species, including substances that selectively induce neurogenesis in the adult mam- humans (Altman and Das, 1965; Kuhn et al., 1996; Eriksson et al., malian CNS in vivo. 1998). Progenitor cells isolated from this region have demon- Insulin-like growth factor-I (IGF-I) is a growth-promoting pep- strated the capacity for self-renewal in vitro; when grafted back tide that is important during development of the brain (Sara and into the adult brain, they have the potential to develop into Carlsson-Skwirut, 1988; Bozyczko-Coyne et al., 1993; Giacobini mature neurons with the phenotypic characteristics of surround- et al., 1995; Dentremont et al., 1999). Overexpression of IGF-I, both peripherally and centrally, in transgenic mice results in an Received Oct. 21, 1999; revised Feb. 7, 2000; accepted Feb. 7, 2000. increase in brain size and myelin content (Carson et al., 1993). This study was supported by grants from the Swedish Medical Research Council Conversely, the number of granule cells in the hippocampus, the (project no. 12X-12535), the Faculty of Medicine of the University of Go¨teborg, the oligodendrocyte and neuron density within the olfactory bulbs, John and Brit Wennerstro¨ms Foundation for Neurological Research, the Rune and Ulla Amlo¨vs Foundation for Neurological and Rheumatological Research, Stiftelsen and total brain size are reduced in knock-out mice (Beck et al., Go¨teborgs MS fo¨renings forsknings och byggnadsfond, Stiftelsen Handlanden Hjal- 1995; Cheng et al., 1998). mar Svenssons Forskningsfond, the Swedish Society of Medicine, Go¨teborgs There are two potential pathways by which IGF-I may affect the La¨karesa¨llskap, the Edit Jacobssons Foundation, Stiftelsen Thure Carlssons Minne, Stiftelsen Lars Hiertas Minne, the Novo Nordisk Foundation, the Åke Wiberg hippocampus. IGF-I receptors expressed in the adult dentate Foundation, the Magnus Bergvalls Foundation, Axel Linders stiftelse, and the Tore gyrus (Lesniak et al., 1988) may be reached by IGF-I either from Nilssons Foundation. We appreciate the technical advice of Ann-Marie Alborn and the periphery (by crossing the blood–brain barrier) (Duffy et al., the assistance of Barbro Eriksson with coding slides. We also want to thank Maria Wågberg and Knut Pettersson at Astra Ha¨ssle Gothenburg for kindly letting us use 1988; Reinhardt and Bondy, 1994) or locally by paracrine IGF-I their microscope. Recombinant human IGF-I was a kind gift from Genentech (South (Breese et al., 1996). In the present study we wanted to assess the San Francisco, CA). We are grateful to Dr. Tommy Johnson at the Department of Statistics (Go¨teborg University, Go¨teborg, Sweden) for the statistical advice and to impact of peripheral, normally liver-derived, IGF-I. Proper English (Alfta, Sweden) for proofreading of this manuscript in English. It is possible that the reported alterations in hippocampal Correspondence should be addressed to Dr. Peter S. Eriksson, Institute of granule cell number in animals with supranormal or subnormal Clinical Neuroscience, Go¨teborg University, Blå Stråket 7, SE-413 45 Go¨teborg, Sweden. E-mail: [email protected]. IGF-I levels occur in part as a result of a perturbation in the Copyright © 2000 Society for Neuroscience 0270-6474/00/202896-08$15.00/0 proliferation of endogenous neural progenitor cells. This hypoth- Åberg et al. • IGF-I Stimulation of Adult Progenitor Stem Cells J. Neurosci., April 15, 2000, 20(8):2896–2903 2897 esis led us to investigate the proliferation and differentiation of Mannheim, Mannheim, Germany), or rabbit anti-GFAP (1:500; Dako, progenitor cells in the adult dentate gyrus in hypophysectomized Glostrup, Denmark) and rat anti-BrdU antibody (1:200; Harlan, Lough- borough, United Kingdom) overnight at 4°C. GFAP and Calbindin D28K (hx) rats treated with peripheral administration of IGF-I. The hx were detected with Texas Red-conjugated anti-rabbit IgG (1:200 for rat is widely used as a model of somatic IGF-I deficiency because GFAP and 1:100 for Calbindin D28K; Jackson ImmunoResearch, West hx animals have low circulating levels of IGF-I (Schoenle et al., Grove, PA), Calbindin D28K was also detected with Cy5-conjugated 1982; Sjo¨berg et al., 1994). We used bromodeoxyuridine (BrdU) anti-rabbit IgG (1:150; Jackson ImmunoResearch), NeuN and MAP2 labeling to monitor proliferation and double or triple immuno- were detected with Texas Red-conjugated anti-mouse IgG (1:100; Jack- son ImmunoResearch), and BrdU was labeled with an FITC-conjugated fluorescent labeling for BrdU and cell-specific markers to deter- anti-rat IgG (1:150; Jackson ImmunoResearch) for 2 hr at 37°C. Immu- mine the phenotype of the progenitor progeny. nofluorescence was detected and processed with a Nikon Diaphot fluo- rescence microscope and confocal laser-scanning microscopy using a Bio-Rad 1024 system (Hercules, CA). MATERIALS AND METHODS Quantification. For each animal, the number of BrdU-positive cells in the granule cell layer (GCL; including the subgranular layer) and in the Animals and hormonal treatment. We used hx rats, which have low hilus and their corresponding sample volumes were determined in 12 circulating levels of IGF-I (Schoenle et al., 1982; Sjo¨berg et al., 1994). immunoperoxidase-stained, 40-␮m-thick coronal sections taken 240 ␮m The effect of IGF-I treatment was shown by comparing the weight gain apart. Area estimations were obtained by planimetry, using a Lucivid in treated versus untreated (control) hx rats (data not shown) (Schoenle device (MicroBrightField, Colchester, VT) attached to a Leica micro- et al., 1982; Fielder et al., 1996). Female Sprague Dawley rats (Mølle- scope. The section thickness of 40 ␮m (microtome setting) was used in gaard Breeding Center, Ejby, Denmark) were hypophysectomized at the dissector estimation of volume. The number of BrdU-positive cells 50 d of age at the Møllegaard Breeding Center. Weight-matched female was counted within the GCL and two cell diameters below the GCL, normal (non-hx) rats were also investigated. All rats were maintained ignoring the cells in the uppermost focal plane and focusing through the under standard conditions of temperature (24–26°C) and humidity (50– thickness of the section to avoid errors caused by oversampling [for a 60%) and with lights on between 05:00 and 19:00 hr. The rats had access discussion of the optical dissector principle, see Gundersen et al. (1988); to water and standard laboratory chow ad libitum. Hormonal treatment West (1993); Coggeshall and Lekan (1996)]. Pictures were taken under a started 7–10 d after hypophysectomy. All hx rats received subcutaneous Nikon microscope equipped with a video camera. The results are ex- injections of cortisol phosphate (400 ␮g/kg per d; Solu-Cortef, Upjohn, pressed as BrdU-positive cells per sample volume per section. We deter- Puurs, Belgium) and L-thyroxine (10 ␮g/kg per d; Nycomed Pharma, mined the total number of BrdU-positive cells in the GCL and in the Oslo, Norway) diluted in saline (08:00 hr) (Sjo¨berg et al., 1994).
Load more

Recommended publications
  • Antidepressants Increase Human Hippocampal Neurogenesis By
    Molecular Psychiatry (2011) 16, 738–750 & 2011 Macmillan Publishers Limited All rights reserved 1359-4184/11 www.nature.com/mp ORIGINAL ARTICLE Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor C Anacker1,2,3, PA Zunszain1, A Cattaneo1,4, LA Carvalho1, MJ Garabedian5, S Thuret3, J Price3 and CM Pariante1,2 1King’s College London, Institute of Psychiatry, Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology (SPI-lab), Department of Psychological Medicine, London, UK; 2National Institute for Health Research ‘Biomedical Research Centre for Mental Health’, Institute of Psychiatry and South London and Maudsley NHS Foundation Trust, London, UK; 3King’s College London, Institute of Psychiatry, Centre for the Cellular Basis of Behaviour (CCBB), London, UK; 4Genetics Unit, IRCCS San Giovanni di Dio, Brescia, Italy and 5Department of Microbiology, NYU School of Medicine, New York, NY, USA Antidepressants increase adult hippocampal neurogenesis in animal models, but the underlying molecular mechanisms are unknown. In this study, we used human hippocampal progenitor cells to investigate the molecular pathways involved in the antidepressant-induced modulation of neurogenesis. Because our previous studies have shown that antidepressants regulate glucocorticoid receptor (GR) function, we specifically tested whether the GR may be involved in the effects of these drugs on neurogenesis. We found that treatment (for 3–10 days) with the antidepressant, sertraline, increased neuronal differentiation via a GR-dependent mechanism. Specifically, sertraline increased both immature, double- cortin (Dcx)-positive neuroblasts ( þ 16%) and mature, microtubulin-associated protein-2 (MAP2)-positive neurons ( þ 26%). This effect was abolished by the GR-antagonist, RU486. Interestingly, progenitor cell proliferation, as investigated by 50-bromodeoxyuridine (BrdU) incorporation, was only increased when cells were co-treated with sertraline and the GR-agonist, dexamethasone, ( þ 14%) an effect which was also abolished by RU486.
    [Show full text]
  • The Antidepressant Effect of Testosterone an Effect Of
    Neurology, Psychiatry and Brain Research 32 (2019) 104–110 Contents lists available at ScienceDirect Neurology, Psychiatry and Brain Research journal homepage: www.elsevier.com/locate/npbr The antidepressant effect of testosterone: An effect of neuroplasticity? T ⁎ Andreas Walthera,b,c, , Joanna Marta Wasielewskad, Odette Leitere a Biological Psychology, Technische Universität Dresden, Dresden, Germany b Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland c Task Force on Men’s Mental Health of the World Federation of the Societies of Biological Psychiatry (WFSBP), Germany d Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Germany e Queensland Brain Institute (QBI), University of Queensland, St Lucia, QLD, 4072, Australia ARTICLE INFO ABSTRACT Keywords: Background: Rodent and human studies indicate that testosterone has an antidepressant effect. The mechanisms Testosterone via which testosterone exerts its antidepressant effect, however, remain to be elucidated. Some studies assume Depression downstream effects of testosterone on sexual function and vitality followed by improvement of mood. Emerging Men evidence suggests that testosterone may be acting in the brain within depression-relevant areas, whereby eli- Neurogenesis citing direct antidepressant effects, potentially via neuroplasticity. Neuroplasticity Methods: Literature was searched focusing on testosterone treatment and depression and depression-like be- Antidepressant havior. Due to the unilateral clinical use of testosterone in men and the different modes of action of sex hor- mones in the central nervous system in men and women, predominantly studies on male populations were identified. Results: The two proposed mechanisms via which testosterone might act as antidepressant in the central nervous system are the support of neuroplasticity as well as the activation of the serotonin system.
    [Show full text]
  • Stress Hormones Trk Neurons Into Survival
    RESEA r CH HIGHLIGHTS M olec U lar ne U roscience Similar to the in vivo experi- ments, Dex treatment of cultured neurons did not increase levels of Stress hormones Trk BDNF, NGF or NT3, suggesting that the neuroprotective effect of Dex is independent of neurotrophin release. neurons into survival Administration of an inhibitor of the PI3K–AKT pathway abolished Dex- which adult neurogenesis occurs. mediated neuroprotection, whereas Surprisingly, Dex administration did adding a Trk inhibitor only reduced not alter levels of the neurotrophins it; thus, glucocorticoids might also nerve growth factor (NGF), brain- stimulate the PI3K–AKT pathway derived neurotrophic factor (BDNF) through a route that does not involve and neurotrophin 3 (NT3) in the hip- TrkB phosphorylation. pocampus or in the parietal cortex, The mechanism by which gluco- indicating that the phosphorylation corticoids activate Trks is unknown of TrkB by glucocorticoids did not but probably involves the gluco- require increased neurotrophin corticoid receptor, as addition of a production. glucocorticoid receptor antagonist Phosphorylated Trks are activated abolished Dex-mediated neuropro- tyrosine kinases, which can phospho- tection. The glucocorticoid effects rylate other proteins. Thus, adding were slow and lasted for several Glucocorticoids have a bad reputa- Dex or BDNF (the main ligand for hours, which is suggestive of genomic tion. However, although these stress the TrkB receptor) to cortical slices actions. Indeed, Trk activation by hormones can be neurotoxic in activated TrkB and phosphorylated Dex could be abolished by actinomy- high levels, they are also required the intracellular signalling molecules cin D and cycloheximine, inhibitors for neuronal survival, and they AKT, phospholipase Cγ (PLCγ) and of transcription and translation, promote neuronal growth and dif- extracellular signal-regulated kinase respectively.
    [Show full text]
  • Trkb Receptor Controls Striatal Formation by Regulating the Number of Newborn Striatal Neurons
    TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons Maryna Baydyuka, Theron Russella, Guey-Ying Liaoa, Keling Zangb, Juan Ji Ana, Louis French Reichardtb, and Baoji Xua,1 aDepartment of Pharmacology, Georgetown University Medical Center, Washington, DC 20057; and bDepartment of Physiology, University of California, San Francisco, CA 94158 Edited* by Michael P. Stryker, University of California, San Francisco, CA, and approved November 19, 2010 (received for review April 8, 2010) In the peripheral nervous system, target tissues control the final son disease (6, 7). Approximately 95% of striatal neurons are size of innervating neuronal populations by producing limited medium-sized spiny neurons (MSNs) with the rest being inter- amounts of survival-promoting neurotrophic factors during de- neurons (8). MSNs, which use γ-aminobutyric acid (GABA) as velopment. However, it remains largely unknown if the same a transmitter, are born in the lateral ganglionic eminence (LGE) principle works to regulate the size of neuronal populations in the and migrate to the striatum during embryogenesis (9). They are developing brain. Here we show that neurotrophin signaling divided into two populations based on their projection sites. mediated by the TrkB receptor controls striatal size by promoting MSNs at the origin of the direct pathway directly project to the the survival of developing medium-sized spiny neurons (MSNs). output nuclei of the basal ganglia, such as the internal segment of Selective deletion of the gene for the TrkB receptor in striatal the globus pallidus, the substantia nigra pars reticulata, and the progenitors, using the Dlx5/6-Cre transgene, led to a hindpaw- ventral pallidum.
    [Show full text]
  • Regulation of Adult Neurogenesis in Mammalian Brain
    International Journal of Molecular Sciences Review Regulation of Adult Neurogenesis in Mammalian Brain 1,2, 3, 3,4 Maria Victoria Niklison-Chirou y, Massimiliano Agostini y, Ivano Amelio and Gerry Melino 3,* 1 Centre for Therapeutic Innovation (CTI-Bath), Department of Pharmacy & Pharmacology, University of Bath, Bath BA2 7AY, UK; [email protected] 2 Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK 3 Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy; [email protected] (M.A.); [email protected] (I.A.) 4 School of Life Sciences, University of Nottingham, Nottingham NG7 2HU, UK * Correspondence: [email protected] These authors contributed equally to this work. y Received: 18 May 2020; Accepted: 7 July 2020; Published: 9 July 2020 Abstract: Adult neurogenesis is a multistage process by which neurons are generated and integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Neurogenesis plays a fundamental role in postnatal brain, where it is required for neuronal plasticity. Moreover, perturbation of adult neurogenesis contributes to several human diseases, including cognitive impairment and neurodegenerative diseases. The interplay between extrinsic and intrinsic factors is fundamental in regulating neurogenesis. Over the past decades, several studies on intrinsic pathways, including transcription factors, have highlighted their fundamental role in regulating every stage of neurogenesis. However, it is likely that transcriptional regulation is part of a more sophisticated regulatory network, which includes epigenetic modifications, non-coding RNAs and metabolic pathways.
    [Show full text]
  • Amitriptyline-Mediated Cognitive Enhancement in Aged 36Tg Alzheimer’S Disease Mice Is Associated with Neurogenesis and Neurotrophic Activity
    Amitriptyline-Mediated Cognitive Enhancement in Aged 36Tg Alzheimer’s Disease Mice Is Associated with Neurogenesis and Neurotrophic Activity Wayne Chadwick1, Nick Mitchell2, Jenna Caroll3, Yu Zhou1, Sung-Soo Park1, Liyun Wang1, Kevin G. Becker4, Yongqing Zhang4, Elin Lehrmann4, William H. Wood III4, Bronwen Martin5, Stuart Maudsley1* 1 Receptor Pharmacology Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America, 2 Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America, 3 Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 4 Genomics Unit, Research Resources Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America, 5 Metabolism Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America Abstract Approximately 35 million people worldwide suffer from Alzheimer’s disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Ab) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long- term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (36TgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Ab monomer with a concomitant decrease in cytotoxic dimer Ab load, compared to vehicle-treated 36TgAD controls.
    [Show full text]
  • Effects of Neuregulin-1 Administration on Neurogenesis in the Adult Mouse
    www.nature.com/scientificreports OPEN Effects of neuregulin-1 administration on neurogenesis in the adult mouse hippocampus, Received: 30 January 2016 Accepted: 04 July 2016 and characterization of immature Published: 29 July 2016 neurons along the septotemporal axis Ian Mahar1,2, Angus MacIsaac1, John Junghan Kim1, Calvin Qiang1, Maria Antonietta Davoli1, Gustavo Turecki1,2,3 & Naguib Mechawar1,2,3 Adult hippocampal neurogenesis is associated with learning and affective behavioural regulation. Its diverse functionality is segregated along the septotemporal axis from the dorsal to ventral hippocampus. However, features distinguishing immature neurons in these regions have yet to be characterized. Additionally, although we have shown that administration of the neurotrophic factor neuregulin-1 (NRG1) selectively increases proliferation and overall neurogenesis in the mouse ventral dentate gyrus (DG), likely through ErbB3, NRG1’s effects on intermediate neurogenic stages in immature neurons are unknown. We examined whether NRG1 administration increases DG ErbB3 phosphorylation. We labeled adultborn cells using BrdU, then administered NRG1 to examine in vivo neurogenic effects on immature neurons with respect to cell survival, morphology, and synaptogenesis. We also characterized features of immature neurons along the septotemporal axis. We found that neurogenic effects of NRG1 are temporally and subregionally specific to proliferation in the ventral DG. Particular morphological features differentiate immature neurons in the dorsal and ventral DG, and cytogenesis differed between these regions. Finally, we identified synaptic heterogeneity surrounding the granule cell layer. These results indicate neurogenic involvement of NRG1-induced antidepressant- like behaviour is particularly associated with increased ventral DG cell proliferation, and identify novel distinctions between dorsal and ventral hippocampal neurogenic development.
    [Show full text]
  • Androgens Enhance Adult Hippocampal Neurogenesis in Males but Not Females in an Age
    bioRxiv preprint doi: https://doi.org/10.1101/539296; this version posted February 3, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Androgens enhance adult hippocampal neurogenesis in males but not females in an age- 2 dependent manner 3 4 Paula Duarte-Guterman1, Dwayne K. Hamson1, Steven R. Wainwright1, Carmen Chow1, Jessica 5 Chaiton1, Stephanie Lieblich1, Neil V. Watson2, Liisa A.M. Galea1 6 7 1. Djavad Mowafaghian Centre for Brain Health and Department of Psychology, University of 8 British Columbia, Vancouver, BC, Canada 9 2. Department of Psychology, Simon Fraser University, Burnaby, BC, Canada 10 11 12 Address all correspondence and requests for reprints to: 13 L. A. M. Galea, PhD, 14 Djavad Mowafaghian Centre for Brain Health 15 2215 Wesbrook Mall 16 Vancouver, British Columbia 17 V6T 1Z3, Canada 18 2136 West Mall, Vancouver, 19 British Columbia, V6T 1Z4, Canada. 20 E-mail: [email protected]. 1 bioRxiv preprint doi: https://doi.org/10.1101/539296; this version posted February 3, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 21 Abstract 22 Androgens (testosterone and dihydrotestosterone) increase adult hippocampal 23 neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor 24 pathway, but it is not known whether androgens regulate neurogenesis in females and whether 25 the effect is age-dependent.
    [Show full text]
  • The Role of Neuregulin–Erbb4 Interactions on the Proliferation and Organization of Cells in the Subventricular Zone
    The role of neuregulin–ErbB4 interactions on the proliferation and organization of cells in the subventricular zone H. T. Ghashghaei*, Janet Weber†, Larysa Pevny*, Ralf Schmid*, Markus H. Schwab†‡, K. C. Kent Lloyd§, David D. Eisenstat¶, Cary Lai†, and E. S. Anton*ʈ *University of North Carolina Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599; †Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; ‡Max-Planck-Institut fu¨r Experimentelle Medizin, 7075 Go¨ttingen, Germany; §Center for Comparative Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616; and ¶Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada R3E 0V9 Communicated by Pasko Rakic, Yale University School of Medicine, New Haven, CT, December 7, 2005 (received for review October 14, 2005) Coordinated regulation of neuronal progenitor differentiation in of receptor heterodimerization (17). Four genes encoding NRGs the subventricular zone (SVZ) is a fundamental feature of adult have been identified [NRG1–4 (18, 19)]. Of these, NRG1 is the neurogenesis. However, the molecular control of this process best-characterized and is known for its biological activities de- remains mostly undeciphered. Here, we investigate the role of scribed as glial growth factor (GGF) and the acetylcholine receptor- neuregulins (NRGs) in this process and show that a NRG receptor, inducing activity [ARIA (20–24)]. Although Ͼ15 alternatively ErbB4, is primarily expressed by polysialylated neural cell adhesion spliced variants of NRG1 have been identified, these can be molecule immature neuroblasts but is also detected in a subset of grouped into three main classes (I, II, and III) based upon the GFAP؉ astroglial cells, ependymal cells, and Dlx2؉ precursors in the structure of their extracellular regions (18).
    [Show full text]
  • The Behavioral and Neurochemical Aspects of the Interaction Between Antidepressants and Unpredictable Chronic Mild Stress
    RESEARCH ARTICLES The Behavioral and Neurochemical Aspects of the Interaction between Antidepressants and Unpredictable Chronic Mild Stress N. V. Kudryashov1,2,3*, T. S. Kalinina1,3, A. A. Shimshirt1, A. V. Volkova1, V. B. Narkevich1, P. L. Naplekova1, K. A. Kasabov1, V. S. Kudrin1, T. A. Voronina1, V. P. Fisenko2 1Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology», Moscow, 125315 Russia 2Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991 Russia 3N.K. Koltsov Institute of Developmental Biology RAS, Moscow, 119334 Russia *E-mail: [email protected] Received September 10, 2019; in final form, January 29, 2020 DOI: 10.32607/actanaturae.10942 Copyright © 2020 National Research University Higher School of Economics. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hy- droxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corre- sponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine – but not of amitriptyline – after a single injection coincided with an increase in the 5-HT turnover in the hippocampus.
    [Show full text]
  • Alpha1a Adrenergic Receptor Influences on Adult Neurogenesis, Cell Fate, Mood, Learning, Memory, Lifespan, and Cancer Incidence Katie Collette
    University of North Dakota UND Scholarly Commons Theses and Dissertations Theses, Dissertations, and Senior Projects January 2015 Alpha1a Adrenergic Receptor Influences On Adult Neurogenesis, Cell Fate, Mood, Learning, Memory, Lifespan, And Cancer Incidence Katie Collette Follow this and additional works at: https://commons.und.edu/theses Recommended Citation Collette, Katie, "Alpha1a Adrenergic Receptor Influences On Adult Neurogenesis, Cell Fate, Mood, Learning, Memory, Lifespan, And Cancer Incidence" (2015). Theses and Dissertations. 1757. https://commons.und.edu/theses/1757 This Dissertation is brought to you for free and open access by the Theses, Dissertations, and Senior Projects at UND Scholarly Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of UND Scholarly Commons. For more information, please contact [email protected]. ALPHA1A ADRENERGIC RECEPTOR INFLUENCES ON ADULT NEUROGENESIS, CELL FATE, MOOD, LEARNING, MEMORY, LIFESPAN, AND CANCER INCIDENCE by Katie M. Collette Bachelor of Science, University of North Dakota, 2010 A Dissertation Submitted to the Graduate Faculty of the University of North Dakota in partial fulfillment of the requirements for the degree of Doctor of Philosophy Grand Forks, North Dakota May 2015 Copyright 2015 Katie Collette ii This thesis, submitted by Katie M. Collette in partial fulfillment of the requirements for the Degree of Doctor of Philosophy from the University of North Dakota, has been read by the Faculty Advisory Committee under whom the work has been done and is hereby approved. __________________________________ Chairperson, Van Doze __________________________________ Holly Brown-Borg __________________________________ Diane Darland __________________________________ James Haselton __________________________________ Joyce Ohm This dissertation meets the standards for appearance, conforms to the style and format requirements of the Graduate School of the University of North Dakota, and is hereby approved.
    [Show full text]
  • Regulation of Neurogenesis by Neurotrophins During Adulthood: Expected and Unexpected Roles
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 09 February 2016 doi: 10.3389/fnins.2016.00026 Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles Marçal Vilar 1* and Helena Mira 2* 1 Neurodegeneration Unit, Unidad Funcional de Investigación de Enfermedades Crónicas-Instituto de Salud Carlos III, Madrid, Spain, 2 Molecular Neurobiology Unit, Unidad Funcional de Investigación de Enfermedades Crónicas-Instituto de Salud Carlos III, Madrid, Spain The subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here, we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin Edited by: receptors in different scenarios, including both expected and unexpected functions. José Luis Trejo, Institute Cajal - Consejo Superior de Keywords: adult neurogenesis, neural stem cell, neurotrophin, p75NTR, TrkB, BDNF, NT3 Investigaciones Científicas, Spain Reviewed by: Stefano Farioli Vecchioli, INTRODUCTION Consiglio Nazionale delle Ricerche, Italy Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central John W.
    [Show full text]