Altered glutamate clearance in ascorbate deficient mice increases seizure susceptibility and contributes to cognitive impairment in APP/PSEN1 mice

Neurobiology of Aging
Deborah J MiFiona Edith Harrison

Abstract

Ascorbate (vitamin C) is critical as a first line of defense antioxidant within the brain, and specifically within the synapse. Ascorbate is released by astrocytes during glutamate clearance and disruption of this exchange mechanism may be critical in mediating glutamate toxicity within the synapse. This is likely even more critical in neurodegenerative disorders with associated excitotoxicity and seizures, in particular Alzheimer's disease, in which ascorbate levels are often low. Using Gulo-/- mice that are dependent on dietary ascorbate, we established that low brain ascorbate increased sensitivity to kainic acid as measured via behavioral observations, electroencephalography (EEG) measurements, and altered regulation of several glutamatergic system genes. Kainic acid-induced immobility was improved in wild-type mice following treatment with ceftriaxone, which upregulates glutamate transporter GLT-1. The same effect was not observed in ascorbate-deficient mice in which sufficient ascorbate is not available for release. A single, mild seizure event was sufficient to disrupt performance in the water maze in low-ascorbate mice and in APPSWE/PSEN1dE9 mice. Together, the data support the critical role of brain ascorbate in mainta...Continue Reading

References

Mar 9, 1996·BMJ : British Medical Journal·C R GaleC Cooper
Jun 1, 1997·Journal of the American Geriatrics Society·W J PerrigH B Stähelin
Jun 1, 1997·The European Journal of Neuroscience·D TrottiA Volterra
Dec 16, 1998·International Journal of Geriatric Psychiatry·S RivièreB Vellas
Apr 16, 1999·Cell Death and Differentiation·J P SteinbachA Aguzzi
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·N MaedaR Reddick
Mar 4, 2000·Brain Research·J X WilsonA W Gelb
Nov 19, 2003·Journal of Alzheimer's Disease : JAD·Joseph QuinnBalz Frei
Oct 7, 2004·Neuroscience·M Schneider OliveiraC F Mello
Mar 17, 2005·Alcoholism, Clinical and Experimental Research·Roberto I MelendezPeter W Kalivas
Aug 30, 2007·Neurochemical Research·Bjørnar HasselPiers C Emson
Aug 16, 2008·Experimental Biology and Medicine·Ankica V JelenkovicBogdan S Boskovic
Jan 20, 2009·Neurobiology of Disease·Wendy K ChungDane M Chetkovich
Jan 24, 2009·Free Radical Biology & Medicine·Fiona E Harrison, James M May
Mar 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rimante MinkevicieneHeikki Tanila
Jul 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Youssef SariGeorge V Rebec
Aug 5, 2009·The Journal of Physiology·Azar OmraniFiorenzo Conti
Sep 1, 2009·Biological Psychiatry·Lori A KnackstedtPeter W Kalivas
Jun 24, 2010·Brain Research·Fiona E HarrisonJames M May
Jul 29, 2010·Journal of Biomedical Science·Youssef SariGeorge V Rebec
Apr 20, 2011·Epilepsy & Behavior : E&B·A J Larner
Nov 11, 2011·CNS Neuroscience & Therapeutics·Daniel FriedmanNikolaos Scarmeas
Oct 31, 2012·Journal of Neurochemistry·Margaret S WardFiona E Harrison
Nov 3, 2012·Epilepsy Currents·Dionysios Pandis, Nikolaos Scarmeas
May 1, 2013·Pharmacology, Biochemistry, and Behavior·Ipek KaramanAhmet Ulugol

❮ Previous
Next ❯

Citations

Aug 17, 2020·Journal of Neurochemistry·David C ConsoliFiona E Harrison
Jan 27, 2020·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Maria Inês TeixeiraPaulo C Costa

❮ 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

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.