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Dernière publication 25/09/2014

Glutamate Carboxypeptidase II Inhibition Behaviorally and Physiologically Improv

Pyridoxine is used as a supplement for treating conditions such as vitamin deficiency as well as neurological disorders such as depression,...

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    [title] => Glutamate Carboxypeptidase II Inhibition Behaviorally and Physiologically Improv
    [paragraph] => Glutamate Carboxypeptidase II Inhibition Behaviorally and Physiologically Improves Pyridoxine-Induced Neuropathy in Rats
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Authors
Potter MC, Wozniak KM, Callizot N, Slusher BS

 Lab
Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Journal
PLoS One
Abstract
Pyridoxine is used as a supplement for treating conditions such as vitamin deficiency as well as neurological disorders such as depression, epilepsy and autism. A significant neurologic complication of pyridoxine therapy is peripheral neuropathy thought to be a result of long-term and high dose usage. Although pyridoxine-induced neuropathy is transient and can remit after its withdrawal, the process of complete recovery can be slow. Glutamate carboxypeptidase II (GCP II) inhibition has been shown to improve symptoms of both chemotherapy- and diabetic-induced neuropathy. This study evaluated if GCP II inhibition could behaviorally and physiologically improve pyridoxine-induced neuropathy. In the current study, high doses of pyridoxine (400 mg/kg, twice a day for seven days) were used to induce neuropathy in rats. An orally bioavailable GCP II inhibitor, 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), was administered daily at a dose of 30 mg/kg starting from the onset of pyridoxine injections. Body weight, motor coordination, heat sensitivity, electromyographical (EMG) parameters and nerve morphological features were monitored. The results show beneficial effects of GCP II inhibition including normalization of hot plate reaction time, foot fault improvements and increased open field distance travelled. H wave frequency, amplitude and latency as well as sensory nerve conduction velocity (SNCV) were also significantly improved by 2-MPPA. Lastly, GCP II inhibition resulted in morphological protection in the spinal cord and sensory fibers in the lumbar region dorsal root ganglia (DRG). In conclusion, inhibition of GCP II may be beneficial against the peripheral sensory neuropathy caused by pyridoxine.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)
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Un outil rapide pour l'évaluation de substances anxiolytiques putatives chez l'animal naïf. Un "must" pour l'étude de l'anxiété, le screening des drogues et le phénotypage.
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