Neurofilament light interaction with GluN1 modulates neurotransmission and schizophrenia-associated behaviors

Translational Psychiatry
Aidong YuanRalph A Nixon

Abstract

Neurofilament (NFL) proteins have recently been found to play unique roles in synapses. NFL is known to interact with the GluN1 subunit of N-methyl-D-aspartic acid (NMDAR) and be reduced in schizophrenia though functional consequences are unknown. Here we investigated whether the interaction of NFL with GluN1 modulates synaptic transmission and schizophrenia-associated behaviors. The interaction of NFL with GluN1 was assessed by means of molecular, pharmacological, electrophysiological, magnetic resonance spectroscopy (MRS), and schizophrenia-associated behavior analyses. NFL deficits cause an NMDAR hypofunction phenotype including abnormal hippocampal function, as seen in schizophrenia. NFL-/- deletion in mice reduces dendritic spines and GluN1 protein levels, elevates ubiquitin-dependent turnover of GluN1 and hippocampal glutamate measured by MRS, and depresses hippocampal long-term potentiation. NMDAR-related behaviors are also impaired, including pup retrieval, spatial and social memory, prepulse inhibition, night-time activity, and response to NMDAR antagonist, whereas motor deficits are minimal. Importantly, partially lowering NFL in NFL+/- mice to levels seen regionally in schizophrenia, induced similar but milder NMDAR-...Continue Reading

References

Jul 1, 1978·Physiology & Behavior·L J Terlecki, R S Sainsbury
Oct 1, 1991·The American Journal of Psychiatry·D C Javitt, S R Zukin
Jun 1, 1967·Journal of Comparative and Physiological Psychology·D P KimbleC W Hendrickson
Dec 1, 1995·Archives of General Psychiatry·J W Olney, N B Farber
Mar 1, 1995·Molecular and Cellular Biology·J SpenceD Finley
Jul 1, 1994·Physiological Reviews·C J McBain, M L Mayer
Jun 1, 1994·Pharmacology, Biochemistry, and Behavior·D M JacksonA Bengtsson
Oct 15, 1998·Journal of Neurology, Neurosurgery, and Psychiatry·L J GareyS R Hirsch
Jan 14, 1999·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J W NewcomerJ W Olney
Mar 4, 1999·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J D Jentsch, R H Roth
May 21, 1999·The European Journal of Neuroscience·P BassandM Khrestchatisky
Jan 13, 2000·Archives of General Psychiatry·L A Glantz, D A Lewis
Jun 22, 2000·Nature Neuroscience·H HusiS G Grant
Aug 16, 2000·American Journal of Physiology. Cell Physiology·A G Therien, R Blostein
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·M D NguyenJ P Julien
Jan 22, 2002·Biological Psychiatry·James F Leckman, Amy E Herman
May 3, 2002·Molecular Psychiatry·J A Badner, E S Gershon
Jul 19, 2002·The Journal of Comparative Neurology·Zaixiang ZhangZuoshang Xu
Jun 13, 2003·American Journal of Human Genetics·Cathryn M LewisTomas Helgason
Mar 12, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Britta QualmannMichael M Kessels
Apr 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Akihiko KatoDavid S Bredt
Sep 29, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Aidong YuanRalph A Nixon
Oct 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Houman Homayoun, Bita Moghaddam
Nov 23, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Monica Beneyto, James H Meador-Woodruff
Aug 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Martin BalastikPeter Gruss
Mar 26, 2009·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Santhosh Girirajan, Sarah H Elsea
May 13, 2009·Behavioural Brain Research·Stephan Bickel, Daniel C Javitt
Jun 16, 2009·Behavioural Brain Research·Fabrício Luiz AssiniReinaldo Naoto Takahashi
Jul 1, 2009·Genes, Brain, and Behavior·T B HaleneS J Siegel
Jul 17, 2009·The New England Journal of Medicine·Fei Li, Joe Z Tsien
Dec 30, 2009·Annals of Neurology·Sabrina W YumSteven S Scherer

❮ Previous
Next ❯

Citations

Jan 24, 2020·Cytoskeleton·Christopher J Bott, Bettina Winckler
May 15, 2020·Brain : a Journal of Neurology·Arie R GafsonPaul M Matthews
May 10, 2020·Acta Neuropathologica Communications·Pooja Shree MishraJean-Pierre Julien
Jan 5, 2019·Journal of Neurovirology·Kristen A McLaurinCharles F Mactutus
Nov 19, 2020·Alzheimer's Research & Therapy·Victor BlonieckiYvonne Freund-Levi
Jan 18, 2021·Current Opinion in Cell Biology·Pascale Bomont
Apr 10, 2021·Journal of Molecular Neuroscience : MN·Julie FourneauErwan Dupont
Jul 9, 2021·Frontiers in Neuroscience·Federico VerdeVincenzo Silani

❮ Previous
Next ❯

Methods Mentioned

BETA
electron microscopy
co-immunoprecipitation
ubiquitination

Software Mentioned

LCModel

Related Concepts

Related Feeds

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.

Addison Disease

Addison's disease, also known as primary adrenal insufficiency and hypocortisolism, is a long-term endocrine disorder in which the adrenal glands do not produce enough steroid hormones. Discover the latest research on Addison's disease here.