---
res:
  bibo_abstract:
  - Glutamate excitotoxicity is a cell death mechanism triggered by accumulation of
    glutamate in the extracellular space. The α-ketoglutarate dehydrogenase complex
    (αKGDHC), an enzyme of the tricarboxylic acid cycle, represents a branching point
    controlling glutamate formation and its consumption as a fuel. Hence, modulation
    of the activity of αKGDHC might alter the amount of glutamate available for excitotoxic
    effects. To address this hypothesis, hippocampal neurons in primary co-culture
    with glial cells were exposed to zero-Mg2 buffer to elicit excitotoxicity through
    N-methyl-D-aspartic acid (NMDA) receptor disinhibition. Pretreatment of the cultures
    with succinyl phosphonate, to inhibit αKGDHC, enhanced excitotoxity, whereas promotion
    of αKGDHC activity by pretreatment with thiamine caused an opposite action. Moreover,
    NMDA receptor currents – but not those mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
    acid (AMPA) receptors – were potentiated in neurons with impaired αKGDHC activity
    and diminished in neurons with boosted αKGDHC activity. The sensitization of NMDA
    receptors involved mGluR1 activation and was accompanied by enhanced neuronal
    discharge activity, elevated basal cytosolic Ca2+ levels, and augmented Ca2+ responses
    evoked by glutamate application. These results suggest that mGluR1-mediated potentiation
    of NMDA receptors contributes to a mechanism by which inhibition of αKGDHC might
    exacerbate glutamate excitotoxicity.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Vanessa
      foaf_name: Goeschl, Vanessa
      foaf_surname: Goeschl
  - foaf_Person:
      foaf_givenName: Matej
      foaf_name: Hotka, Matej
      foaf_surname: Hotka
  - foaf_Person:
      foaf_givenName: Bernhard
      foaf_name: Hochreiter, Bernhard
      foaf_surname: Hochreiter
      foaf_workInfoHomepage: http://www.librecat.org/personId=e6cab3de-17f6-11ed-9210-c1e42e045e9d
  - foaf_Person:
      foaf_givenName: Karlheinz
      foaf_name: Hilber, Karlheinz
      foaf_surname: Hilber
  - foaf_Person:
      foaf_givenName: Stefan
      foaf_name: Boehm, Stefan
      foaf_surname: Boehm
  - foaf_Person:
      foaf_givenName: Andrey V.
      foaf_name: Kozlov, Andrey V.
      foaf_surname: Kozlov
  - foaf_Person:
      foaf_givenName: Helmut
      foaf_name: Kubista, Helmut
      foaf_surname: Kubista
  bibo_doi: 10.1242/jcs.264420
  bibo_issue: '8'
  bibo_volume: 139
  dct_date: 2026^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/0021-9533
  - http://id.crossref.org/issn/1477-9137
  dct_language: eng
  dct_publisher: The Company of Biologists@
  dct_title: α-ketoglutarate dehydrogenase complex activity modulates glutamate excitotoxicity
    via metabotropic regulation of NMDA receptors in primary cultures@
  fabio_hasPubmedId: '41834724'
...