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ISSN 2992-779X (Electronic)
ISSN 2007-6452 (Print)

2013, Number 1

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Investigación en Discapacidad 2013; 2 (1)

Long-term effects of 3-nitropropionic acid and quinolinic acid subtoxic levels administration in nucleus striatus of rats

Fuentes-Bello AC, Pérez-Carrera D, Pérez-de la Cruz V, Santamaría-del Ángel A, Carrillo-Mora P

Language: Spanish
References: 28
Page: 3-11
PDF size: 131.80 Kb.


ABSTRACT

Introduction: Excitotoxicity and impaired energy metabolism are two events involved in the neuronal damage observed in neurodegenerative diseases. 3-nitropropionic acid and quinolinic acid are two toxins widely used to reproduce mechanisms of energy metabolism dysfunction and excitotoxicity, respectively; however, it is unknown whether the co-administration of quinolinic acid and 3NP at subtoxic dose may have additive effects on long-term. Objective: To determine the long-term effects of 3-nitropropionic acid and quinolinic acid subtoxic administration on lipid peroxidation levels, mitochondrial functionality, total striatal gamma-aminobutyric acid levels and cell morphology of the striatum neurons in rats. Methods: Male Wistar rats (260-300 g) were used and four groups were formed (n = 7-8; 3-4 rats for biochemical test and 4 rats for morphological analysis): 1) Control: 1 µL intrastriatal (ie) saline and 0.5 mL intraperitoneally (ip) saline solution administration; 2) subtoxic 3-NP (9 mg/kg) ip; 3) Subtoxic quinolinic acid (120 nM/µL) ie; and 4) subtoxic 3NP + subtoxic quinolinic acid. After thirty days after the peroxidation levels and mitochondrial functionality (both in striatal synaptosomes), striatal cell morphology, and total striatal gamma aminobutyric acid levels were evaluated. Results: In the subtoxic co-administration group there was a significant increase in peroxidation levels and in the number of striatal damaged cells, and also a significant decrease of mitochondrial functionality with respect to subtoxic and control groups. Moreover, the total striatal gamma aminobutyric acid content showed a decrease in the subtoxic co-administration group relative to the control but this reduction was not significant. Conclusion: This model confirms that subtoxic co-administration of 3-nitropropionic acid and quinolinic acid may produce a toxic facilitation effect in the long-term. This study suggests that the coexistence of subtle alterations of energy metabolism and excitotoxicity can trigger toxic mechanisms at a larger scale.


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