Alcohol-induced neurodegeneration, suppression of transforming growth factor-beta, and cognitive impairment in rats: prevention by group II metabotropic glutamate receptor activation

Biological Psychiatry
Andrea CippitelliMarkus Heilig

Abstract

Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown. Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol. Following 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-beta (TGF-beta) staining were carried out, and reversal learning in the Morris water maze was assessed. Fluoro-Jade B staining indicating neurodegeneration was most extensive in the ventral hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective in the EC but not in the dentate gyrus of the hippocampus. In parallel, binge alcohol exposure suppressed TGF-beta expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-beta in the EC only. Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning. Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-beta in alcohol-induced neurodegeneration.

References

Jun 24, 1982·Nature·R G MorrisJ O'Keefe
Sep 1, 1994·Pharmacology, Biochemistry, and Behavior·A P CruzF G Graeff
Jul 1, 1993·Behavioral and Neural Biology·L E Jarrard
Nov 1, 1996·Alcoholism, Clinical and Experimental Research·J Y ZouM A Collins
Dec 5, 2000·Alcoholism, Clinical and Experimental Research·F T CrewsD J Knapp
Aug 23, 2001·Brain Research. Brain Research Reviews·R D'Hooge, P P De Deyn
Aug 29, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·V BrunoF Nicoletti
May 1, 2002·Alcoholism, Clinical and Experimental Research·J A ObernierF T Crews
Aug 15, 2002·Pharmacology, Biochemistry, and Behavior·Jennifer A ObernierFulton T Crews
Jun 21, 2003·Science·Constance Holden
Apr 29, 2004·Alcoholism, Clinical and Experimental Research·Fulton T CrewsAntonio Noronha
May 4, 2004·Trends in Pharmacological Sciences·Paul J Kenny, Athina Markou
Jan 25, 2005·Nature Reviews. Drug Discovery·Chad J SwansonDarryle D Schoepp
Apr 19, 2005·Psychopharmacology·Edith V Sullivan, Adolf Pfefferbaum
May 10, 2005·The Journal of Pharmacology and Experimental Therapeutics·Carol HamelinkRobert L Eskay
May 12, 2006·Pharmacology, Biochemistry, and Behavior·Fabiana M CarvalhoAngela M Ribeiro
Aug 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Corrado CortiValeria Bruno
Oct 2, 2007·Neurobiology of Learning and Memory·Ian A MendezBarry Setlow

❮ Previous
Next ❯

Citations

Sep 3, 2013·Psychopharmacology·Andrew HolmesJohn H Krystal
Jul 23, 2011·Progress in Neurobiology·John W Wright, Joseph W Harding
Sep 21, 2010·Neurobiology of Learning and Memory·Andrea CippitelliMarkus Heilig
Sep 17, 2015·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Ming TongSuzanne M de la Monte
May 5, 2012·Journal of Zhejiang University. Science. B·Wei-xing ChenHuai-zhuang Ye
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lauren DePoyAndrew Holmes
Dec 21, 2010·Brain, Behavior, and Immunity·Graham A W RookCharles L Raison
Nov 19, 2014·Addiction Biology·Marcus W Meinhardt, Wolfgang H Sommer
Oct 16, 2013·Alcoholism, Clinical and Experimental Research·Rajiv G AgrawalSusan E Bergeson
Apr 8, 2014·Molecular Neurobiology·Michael A CollinsEdward J Neafsey
Mar 26, 2019·Journal of Alzheimer's Disease : JAD·Kevin N HascupErin R Hascup
Feb 11, 2020·Frontiers in Behavioral Neuroscience·Rodrigo G MiraWaldo Cerpa
May 1, 2021·Brain Sciences·Natalie N NawarawongKimberly Nixon
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga NosovaGeorgy Bakalkin
Nov 3, 2010·Neuropharmacology·F NicolettiJ P Pin

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

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.

© 2021 Meta ULC. All rights reserved