Neuroprotective role of monocarboxylate transport during glucose deprivation in slice cultures of rat hippocampus.
The effects of energy substrate removal and metabolic pathway block have been examined on neuronal and glial survival in organotypic slice cultures of rat hippocampus. Slice cultures resisted 24 h of exogenous energy substrate deprivation. Application of 0.5 mM alpha-cyano-4-hydroxycinnamate (4-CIN) for 24 h resulted in specific damage to neuronal cell layers, which could be reversed by co-application of 5 mM lactate. Addition of 10 mM 2-deoxyglucose in the absence of exogenous energy supply produced widespread cell death throughout the slice. This was partly reversed by co-application of 5 mM lactate. These effects of metabolic blockade on cell survival were qualitatively similar to the effects on population spikes recorded in the CA1 cell layer following 60 min application of these agents. The data suggest that monocarboxylate trafficking from glia to neurons is an essential route for supply of energy substrates to neurons particularly when exogenous energy supply is restricted.
Centre for Neurosciences, Southampton General Hospital, Tremona Road, Southampton SO16 6YD and Neuroscience Research, SmithKline Beecham Pharmaceuticals, NFSP (North), Third Avenue, Harlow, Essex CM19 5AW, UK.
H L
HL
Cater
C D
CD
Benham
L E
LE
Sundstrom
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003373:Coumaric Acids / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004338:Drug Combinations; D004594:Electrophysiology; D004734:Energy Metabolism; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D003373:Coumaric Acids; D004338:Drug Combinations; C007175:alpha-cyano-4-hydroxycinnamate; D019344:Lactic Acid; D003847:Deoxyglucose; D005947:Glucose