Short Communication

Metabolic Brain Disease

, Volume 28, Issue 1, pp 111-115

First online:

Undernutrition upregulates fumarate hydratase in the rat nucleus accumbens

  • E. Lizárraga-MollinedoAffiliated withBioquímica y Biología Molecular, Facultad Farmacia, Universidad Complutense de MadridCIBER de Diabetes y Enfermedades Metabólicas Asociadas, ISCIII
  • , C. ÁlvarezAffiliated withBioquímica y Biología Molecular, Facultad Farmacia, Universidad Complutense de MadridCIBER de Diabetes y Enfermedades Metabólicas Asociadas, ISCIII
  • , E. Fernández-MillánAffiliated withCIBER de Diabetes y Enfermedades Metabólicas Asociadas, ISCIII
  • , F. EscriváAffiliated withBioquímica y Biología Molecular, Facultad Farmacia, Universidad Complutense de MadridCIBER de Diabetes y Enfermedades Metabólicas Asociadas, ISCIII
  • , C. González-MartínAffiliated withUnidad de Investigación Traslacional, Hospital General Universitario de Ciudad RealLaboratorio de Farmacología y Toxicología, Universidad San Pablo CEU
  • , E. SalasAffiliated withUnidad de Investigación Traslacional, Hospital General Universitario de Ciudad Real
  • , J. M. Pérez-OrtizAffiliated withUnidad de Investigación Traslacional, Hospital General Universitario de Ciudad Real
  • , L. F. AlguacilAffiliated withUnidad de Investigación Traslacional, Hospital General Universitario de Ciudad RealLaboratorio de Farmacología y Toxicología, Universidad San Pablo CEU Email author 

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Abstract

Previous comparative studies of fumarate hydratase (FH) protein density revealed that the enzyme was overexpressed in the striatum of rodents that are less influenced by rewarding stimuli, from cocaine to food. Therefore, we recently proposed FH as a potential striatal biomarker of brain reward deficiency and addiction vulnerability. This work has been focused to investigate FH activity in the Nucleus Accumbens (NAc) of undernourished rats, taking into account that malnutrition has been related to increased responsiveness to food and drug reward. To this end, we have studied adult female Wistar rats severely food restricted from the 16th day of intrauterine life until adulthood. Animals were sacrificed to dissect the NAc and obtain mitochondrial and cytosolic fractions after homogenisation and centrifugation. FH activity was measured by conversion of malate to fumarate, and protein levels were compared by Western blot analysis when fractions showed differences in activity. Undernutrition did not change cytosolic FH activity but led to a marked increase of mitochondrial FH activity (72 %) and protein content (50 %) in the NAc. This change was in the opposite direction that one would predict if it was related to addiction vulnerability of some kind, but strongly suggests that mitochondrial FH needs to be at some optimal level for normal reward responsiveness.

Keywords

Fumarate hydratase Malnutrition Nucleus accumbens Brain reward