Desipramine targets astrocytes to attenuate synaptic plasticity via modulation of the ephrinA3/EphA4 signalling

Neuropharmacology
Sascha TanasicB Di Benedetto

Abstract

Long-term potentiation (LTP), a major cellular correlate of memory storage, depends on activation of the ERK/MAPK signalling pathway, but the cell type-specific localization of activated MAPKs remains unknown. We found that in the CA1 field of the hippocampus, shortly after LTP induction, an increase in the number of MAPK-positive cells occurred specifically among astrocytes of the stratum radiatum, suggesting a putative role of astrocytes for LTP. Desipramine (DMI) is an antidepressant which is used to treat major depressive disorder, but also other pathologies such as neuropathic pain or attention-deficit/hyperactivity disorder. Tricyclic antidepressants such as DMI may cause memory impairment as a side effect. However, biological underpinnings of this effect still remain unclear. Here, we show that DMI inhibited the astrocytic MAPK activation and thereby hindered synaptic potentiation. These effects correlated with a reduced neuronal activation in the stratum pyramidale, thereby prompting us to analyse a regulator of LTP located at the astrocyte-neuron interface in the stratum radiatum, namely the ephrinA3/EphA4 signalling pathway. DMI enhanced EphA4 clustering, which favoured an increased ephrinA3-mediated EphA4 phosphoryla...Continue Reading

References

Jan 1, 1987·Progress in Neuro-psychopharmacology & Biological Psychiatry·S C Dilsaver, R Davidson
Oct 4, 1996·The Journal of Biological Chemistry·J D English, J D Sweatt
Nov 24, 1999·Canadian Journal of Physiology and Pharmacology·A AraqueP G Haydon
Dec 24, 2002·Nature Neuroscience·Keith K MuraiElena B Pasquale
Mar 12, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A Bortolozzi, F Artigas
Jul 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bernd Knöll, Uwe Drescher
Oct 30, 2004·The American Journal of Psychiatry·Poul Videbech, Barbara Ravnkilde
Sep 2, 2005·Nature Reviews. Neuroscience·J Paige Adams, Serena M Dudek
Sep 8, 2005·Current Opinion in Neurobiology·Nicola J Allen, Ben A Barres
Jan 12, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hideko Nishida, Shigeo Okabe
Jan 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shuo ZhangMaria A Morabito
Apr 25, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Barbara Di BenedettoSabine M Hölter
Jul 16, 2008·Physiological Reviews·Dionysia T TheodosisStéphane H R Oliet
Nov 26, 2008·Nature Neuroscience·Rüdiger Klein
Dec 5, 2008·Molecular Biotechnology·Barbara Di BenedettoRalf Kühn
Dec 17, 2008·The European Journal of Neuroscience·Philip J WelsbyRoger Anwyl
Mar 17, 2009·Science·Jin-Hee HanSheena A Josselyn
Jul 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Maria A CarmonaElena B Pasquale
Aug 20, 2009·Experimental Brain Research·Clive R BramhamKarin Wibrand
Sep 8, 2009·Nature Neuroscience·Alessandro FilosaRüdiger Klein
May 18, 2010·Current Opinion in Neurobiology·Sónia Paixão, Rüdiger Klein
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Carol L PeeblesSteven Finkbeiner
Feb 1, 2011·Nature Neuroscience·Jason D Shepherd, Mark F Bear
Apr 22, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jürgen ZschockeTheo Rein
Jul 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Monique LavialleAmin Derouiche
Feb 22, 2012·The International Journal of Neuropsychopharmacology·Vanja DuricRonald S Duman
Apr 10, 2012·Medicinski Arhiv·Nastaran Eizadi-MoodBehnaz Mohammad-Ebrahimi
May 10, 2012·Cellular Signalling·María Pilar Sánchez-BailónJorge Martín-Pérez
Sep 3, 2013·Current Neuropharmacology·B Di Benedetto, R Rupprecht
Dec 17, 2014·Cold Spring Harbor Perspectives in Biology·Philip G Haydon, Maiken Nedergaard

❮ Previous
Next ❯

Citations

Dec 30, 2016·Oncotarget·Barbara Di Benedetto
Jul 10, 2020·The European Journal of Neuroscience·Celia RomanBarbara Di Benedetto
Mar 15, 2020·Journal of Neuroscience Research·Victoria A MalikBarbara Di Benedetto

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

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.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.