GM1 ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole.

Abstract

Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). In this study, we show that GA inhibits Na+,K+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances-TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 micromol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na+,K+-ATPase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na+,K+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance ex vivo. In addition, GM1 (50-200 microM) protected against Na+,K+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 micromol/striatum) seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na+,K+-ATPase and GABA(A) receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1.

• Authors: Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, Mauro Schneider Oliveira, Natália Gindri Fiorenza, Roberto Frussa-Filho, João Carlos Petry, Rafael Correa Coelho, Carlos Fernando Mello
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 22 Issue 3 Pg. 611-23 (Jun 2006) ISSN: 0969-9961 [Print] United States
• PMID: 16516483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Convulsants
• Excitatory Amino Acid Antagonists
• GABA Agonists
• Glutarates
• Neuroprotective Agents
• Receptors, GABA-A
• Thiobarbituric Acid Reactive Substances
• Muscimol
• G(M1) Ganglioside
• Dizocilpine Maleate
• Sodium-Potassium-Exchanging ATPase
• glutaric acid
• Pentylenetetrazole

Topics

• Animals
• Convulsants (toxicity)
• Dizocilpine Maleate (pharmacology)
• Electroencephalography
• Excitatory Amino Acid Antagonists (pharmacology)
• G(M1) Ganglioside (pharmacology)
• GABA Agonists (pharmacology)
• Glutarates (administration & dosage, toxicity)
• Injections, Intraventricular
• Male
• Muscimol (pharmacology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Pentylenetetrazole (toxicity)
• Protein Carbonylation (drug effects)
• Rats
• Rats, Wistar
• Receptors, GABA-A (drug effects)
• Seizures (chemically induced, prevention & control)
• Sodium-Potassium-Exchanging ATPase (drug effects)
• Thiobarbituric Acid Reactive Substances (metabolism)