Cortical consequences of in vivo blockade of monocarboxylate transport during brain development in mice.
In addition to glucose, monocarboxylates including lactate represent a major source of energy for the developing brain and appears to be crucial in the pathogenesis and recovery after brain damage. We hypothesized a role of monocarboxylates transport in the energy supply of neurons of the immature cerebral cortex. The effects of the blockade of monocarboxylates transport in vivo on the cortical development was investigated in neonatal mice using alpha-cyano-4-hydroxycinnamate (CIN) diluted either in DMSO (CD) or in ethanol (CE) administered intraperitoneally over postnatal day (P) P1 to P3. Injection of CIN induced a cytoarchitectonic disorganization in the parietal cortex likely due to a combination of slight disturbance of cortical neuronal migration and an increased neuronal cell death observed in CE (p < 0.05) but not in CD group. An increased number of activated GFAP-positive astroglia was observed in the neocortex in groups treated with CIN (CD and CE) on P10. These data: 1) Provide first evidence of deleterious effects observed in vivo after blockade of monocarboxylates transport in the developing brain; 2) emphasize the role of lactate during neuronal migration as a major source of energy; and 3) suggest the synergistic effect of ethanol-induced hypoglycemia in cortical brain damage induced by CIN.
Adle-Biassette
Homa
H
INSERM U676 and Paris 7 University, Paris 75019, France.
Olivier
Paul
P
Verney
Catherine
C
Fontaine
Romain H
RH
Evrard
Phillippe
P
Hénin
Dominique
D
Massias
Laurent
L
Gressens
Pierre
P
Baud
Olivier
O
D000818:Animals; D000831:Animals, Newborn; D002264:Carboxylic Acids / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors*; D010641:Phenotype
D002264:Carboxylic Acids; D003373:Coumaric Acids; D027501:Monocarboxylic Acid Transporters; C007175:alpha-cyano-4-hydroxycinnamate