Changes in metabolic substrates after prolonged astrocytes dysfunction and dopaminergic neurons degeneration in substantia nigra

• Autorzy: Kuter K. , Olech L. , Glowacka U.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Underlying cause of movement disorder in Parkinson’s disease is degeneration of dopaminergic neurons in substantia nigra (SN). Supportive role of astrocytes in neuronal energy metabolism was reported. Prolonged dysfunction of astrocytes could increase dopaminergic neurons vulnerability. Our aim was to investigate if prolonged metabolic inhibition of astrocytes influences dopaminergic neurons metabolic substrates utilization. METHODS: Rat model of selective nigrostriatal dopaminergic system degeneration was induced by injection of 6-hydroxydopamine (6-OHDA) into medial forebrain bundle. Astrocytes metabolic dysfunction was caused by 7-days infusion of fluorocitrate (FC) into SN. RESULTS: Densytometric analysis of astrocytes marker – GFAP showed decreased staining after FC treatment. After 4 weeks this effect was diminished suggesting regrowth of astrocytes. 6-OHDA injection caused smaller decreases. FC infusion for 7 days decreased tissue levels of succinate and lactate in SN. Lesioning of dopaminergic neurons increased succinate but decreased lactate levels. Combined treatment neutralized effect on succinate but aggravated lactate decrease. 4 weeks after operation and FC withdrawal lactate levels increased while lesion effect was normalized. At this timepoint profile of the changes on succinate was the same as after one week. Beta-hydroxybutyrate levels significantly increased after FC and dopaminergic lesion and combined effect was enhanced at 7th day. After 4 weeks all groups still showed slightly elevated levels. CONCLUSIONS: 7-day FC administration caused prolonged metabolic dysfunction of astrocytes and influenced dopaminergic neurons metabolism. We suggest that enhanced production of succinate and ketone bodies after dopaminergic neurons degeneration could be one of metabolic compensatory mechanisms. Study supported by the Statutory Funds of the Institute of Pharmacology, PAS, Poland and NCN grant nr 2012/05/B/NZ4/02599.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S60

Twórcy

autor

Kuter K.

• Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
• Physical Biochemistry, Department of Chemistry, Technische Universitat Darmstadt, Darmstadt, Germany

autor

Olech L.

• Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Glowacka U.

• Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland