Endogenous monocarboxylates sustain hippocampal synaptic function and morphological integrity during energy deprivation

Yukitoshi Izumi, Ann M. Benz, Hiroshi Katsuki, Charles F. Zorumski

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Abstract

The ability to fuel neurons via glycogenolysis is believed to be an important function of gila. Indeed, the slow, rather than immediate, depression of synaptic transmission in hippocampal slices during exogenous glucose deprivation suggests that intrinsic energy reservoirs help to sustain neurotransmission. It is believed that gila fuel neighboring neurons via diffusible monocarboxylates such as pyruvate and lactate, although a role for glucose has been proposed also. Using α-cyano-4-hydroxycinnamate (4-CIN) to inhibit monocarboxylate transport and cytochalasin B (CCB) to inhibit glucose transport, we examined the role of glucose and monocarboxylates in supporting the functional and morphological integrity of hippocampal neurons during glucose deprivation. Although 200 μM 4-CIN failed to depress EPSPs supported by 10 mM glucose, pretreatment with 4-CIN accelerated the depression of EPSPs during glucose deprivation. 4-CIN also accelerated the decline in glucose- supported EPSPs after administration of 50 μM CCB, whereas CCB failed to alter the slow decay of pyruvate-supported EPSPs during pyruvate deprivation. 4-CIN did not alter the morphology of pyramidal neurons in the presence of 10 mM glucose but produced significant damage during glucose deprivation or CCB administration. These results suggest that endogenous monocarboxylates rather than glucose maintain neuronal integrity during energy deprivation. Furthermore, EPSPs supported by 2-3.3 mM glucose were sensitive to 4-CIN, suggesting that endogenous monocarboxylates are involved in maintaining neuronal function even under conditions of mild glucose deprivation.

Original languageEnglish
Pages (from-to)9448-9457
Number of pages10
JournalJournal of Neuroscience
Volume17
Issue number24
DOIs
StatePublished - 1997

Keywords

  • Energy metabolism
  • Glucose transport
  • Hippocampus
  • Lactate
  • Neuroglial interactions
  • Pyruvate

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