PMID- 28576943
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20240717
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 37
IP  - 27
DP  - 2017 Jul 5
TI  - Polysialic Acid Regulates Sympathetic Outflow by Facilitating Information 
      Transfer within the Nucleus of the Solitary Tract.
PG  - 6558-6574
LID - 10.1523/JNEUROSCI.0200-17.2017 [doi]
AB  - Expression of the large extracellular glycan, polysialic acid (polySia), is 
      restricted in the adult, to brain regions exhibiting high levels of plasticity or 
      remodeling, including the hippocampus, prefrontal cortex, and the nucleus of the 
      solitary tract (NTS). The NTS, located in the dorsal brainstem, receives constant 
      viscerosensory afferent traffic as well as input from central regions controlling 
      sympathetic nerve activity, respiration, gastrointestinal functions, hormonal 
      release, and behavior. Our aims were to determine the ultrastructural location of 
      polySia in the NTS and the functional effects of enzymatic removal of polySia, 
      both in vitro and in vivo polySia immunoreactivity was found throughout the adult 
      rat NTS. Electron microscopy demonstrated polySia at sites that influence 
      neurotransmission: the extracellular space, fine astrocytic processes, and 
      neuronal terminals. Removing polySia from the NTS had functional consequences. 
      Whole-cell electrophysiological recordings revealed altered intrinsic membrane 
      properties, enhancing voltage-gated K(+) currents and increasing intracellular 
      Ca(2+) Viscerosensory afferent processing was also disrupted, dampening 
      low-frequency excitatory input and potentiating high-frequency sustained currents 
      at second-order neurons. Removal of polySia in the NTS of anesthetized rats 
      increased sympathetic nerve activity, whereas functionally related enzymes that 
      do not alter polySia expression had little effect. These data indicate that 
      polySia is required for the normal transmission of information through the NTS 
      and that changes in its expression alter sympathetic outflow. polySia is abundant 
      in multiple but discrete brain regions, including sensory nuclei, in both the 
      adult rat and human, where it may regulate neuronal function by mechanisms 
      identified here.SIGNIFICANCE STATEMENT All cells are coated in glycans (sugars) 
      existing predominantly as glycolipids, proteoglycans, or glycoproteins formed by 
      the most complex form of posttranslational modification, glycosylation. How these 
      glycans influence brain function is only now beginning to be elucidated. The 
      adult nucleus of the solitary tract has abundant polysialic acid (polySia) and is 
      a major site of integration, receiving viscerosensory information which controls 
      critical homeostatic functions. Our data reveal that polySia is a determinant of 
      neuronal behavior and excitatory transmission in the nucleus of the solitary 
      tract, regulating sympathetic nerve activity. polySia is abundantly expressed at 
      distinct brain sites in adult, including major sensory nuclei, suggesting that 
      sensory transmission may also be influenced via mechanisms described here. These 
      findings hint at the importance of elucidating how other glycans influence neural 
      function.
CI  - Copyright (c) 2017 the authors 0270-6474/17/376559-17$15.00/0.
FAU - Bokiniec, Phillip
AU  - Bokiniec P
AUID- ORCID: 0000-0002-3139-4765
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia.
AD  - Max Delbruck Center for Molecular Medicine, Robert-Roessle-Str. 10, Berlin, 
      13092, Germany.
FAU - Shahbazian, Shila
AU  - Shahbazian S
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia.
FAU - McDougall, Stuart J
AU  - McDougall SJ
AUID- ORCID: 0000-0002-8778-675X
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, 3010 Victoria, Australia.
FAU - Berning, Britt A
AU  - Berning BA
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia.
FAU - Cheng, Delfine
AU  - Cheng D
AUID- ORCID: 0000-0002-8575-0534
AD  - School of Medical Sciences, Discipline of Anatomy and Histology, University of 
      Sydney, Sydney, 2006 New South Wales, Australia.
FAU - Llewellyn-Smith, Ida J
AU  - Llewellyn-Smith IJ
AUID- ORCID: 0000-0003-4269-6846
AD  - Cardiovascular Medicine and Human Physiology, Flinders University, Adelaide, 5042 
      South Australia, Australia.
FAU - Burke, Peter G R
AU  - Burke PGR
AUID- ORCID: 0000-0002-6896-3298
AD  - Neuroscience Research Australia, Sydney, 2031 New South Wales, Australia.
FAU - McMullan, Simon
AU  - McMullan S
AUID- ORCID: 0000-0002-9854-1029
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia.
FAU - Muhlenhoff, Martina
AU  - Muhlenhoff M
AUID- ORCID: 0000-0002-6070-8241
AD  - Institut fur Zellulare Chemie, Medizinische Hochschule Hannover, Hannover 30625, 
      Germany.
FAU - Hildebrandt, Herbert
AU  - Hildebrandt H
AUID- ORCID: 0000-0002-1044-0881
AD  - Institut fur Zellulare Chemie, Medizinische Hochschule Hannover, Hannover 30625, 
      Germany.
FAU - Braet, Filip
AU  - Braet F
AD  - School of Medical Sciences, Discipline of Anatomy and Histology, University of 
      Sydney, Sydney, 2006 New South Wales, Australia.
AD  - Australian Centre for Microscopy and Microanalysis, University of Sydney, Sydney, 
      2006 New South Wales, Australia.
FAU - Connor, Mark
AU  - Connor M
AUID- ORCID: 0000-0003-2538-2001
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia.
FAU - Packer, Nicolle H
AU  - Packer NH
AUID- ORCID: 0000-0002-7532-4021
AD  - ARC Centre of Excellence in Nanoscale Biophotonics, Macquarie University, Sydney, 
      2109 New South Wales, Australia, and.
FAU - Goodchild, Ann K
AU  - Goodchild AK
AUID- ORCID: 0000-0003-1544-7924
AD  - Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 
      Macquarie University, Sydney, 2109 New South Wales, Australia, 
      ann.goodchild@mq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170602
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Sialic Acids)
RN  - 0 (polysialic acid)
SB  - IM
MH  - Afferent Pathways/*physiology
MH  - Animals
MH  - Excitatory Postsynaptic Potentials/physiology
MH  - Male
MH  - Nerve Net/*physiology
MH  - Neuronal Plasticity/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sialic Acids/*metabolism
MH  - Solitary Nucleus/*physiology
MH  - Sympathetic Nervous System/*physiology
MH  - Tissue Distribution
PMC - PMC6596603
OTO - NOTNLM
OT  - electron microscopy
OT  - nucleus of the solitary tract
OT  - patch clamp
OT  - polysialic acid
OT  - sympathetic nerve activity
OT  - viscerosensory afferents
EDAT- 2017/06/04 06:00
MHDA- 2017/08/19 06:00
PMCR- 2018/01/05
CRDT- 2017/06/04 06:00
PHST- 2017/01/19 00:00 [received]
PHST- 2017/05/15 00:00 [revised]
PHST- 2017/05/25 00:00 [accepted]
PHST- 2017/06/04 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2017/06/04 06:00 [entrez]
PHST- 2018/01/05 00:00 [pmc-release]
AID - JNEUROSCI.0200-17.2017 [pii]
AID - 0200-17 [pii]
AID - 10.1523/JNEUROSCI.0200-17.2017 [doi]
PST - ppublish
SO  - J Neurosci. 2017 Jul 5;37(27):6558-6574. doi: 10.1523/JNEUROSCI.0200-17.2017. 
      Epub 2017 Jun 2.