The possible mechanism of Parkinson's disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine

Brain Res. 2014 Dec 10:1592:73-81. doi: 10.1016/j.brainres.2014.09.053. Epub 2014 Oct 5.

Abstract

The progressive pathogenesis and prevention of Parkinson's disease (PD) remains unknown at present. Therefore, the present study aimed to investigate the possible progressive pathogenesis and prevention of PD. Our study investigated the content of glutamate, mitochondria calcium, calmodulin, malonaldehyde and trace elements in striatum, cerebral cortex and hippocampus tissues; and the expression of bcl-2, bax and neuronal nitric oxide synthase (nNOS) in substantia nigra and striatum; and the change of apomorphine induced rotation behavior; and the treatmental effect of monosialotetrahexosylganglioside (GM1) intraperitoneal administration for 14 days in a PD rat model induced by 6-hydroxydopamine. The results revealed that the content of glutamate significantly decreased, and that of mitochondria calcium, calmodulin, malonaldehyde and ferrum significantly increased in striatum, cerebral cortex and hippocampus tissues; the content of magnesium significantly decreased, and that of cuprum and zinc significantly increased in cerebral cortex; the expression of bcl-2 significantly decreased, and that of bax and nNOS significantly increased in substantia nigra and striatum in PD rat. GM1 can partially improve the apomorphine induced rotation behavior and changes of glutamate, mitochondria calcium, calmodulin content in striatum of PD rat. Data suggested that dysfunction of excitatory amino acids neurotransmitter, calcium homeostasis disorder, abnormal metabolism of oxygen free radicals, abnormal trace elements distribution and/or deposition and excessive apoptosis participated in the progressive process of PD, and that GM1 could partially prevent the progressive damage.

Keywords: Apoptosis; Calmodulin; Excitatory amino acid; Malonaldehyde; Mitochondria calcium; Monosialotetrahexosylganglioside; Neuronal nitric oxide synthase; Parkinson’s disease; Trace elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / physiopathology*
  • Calcium / metabolism
  • Calmodulin / metabolism
  • Disease Progression
  • G(M1) Ganglioside / administration & dosage*
  • Glutamic Acid / metabolism
  • Infusions, Parenteral
  • Male
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Nitric Oxide Synthase Type I / metabolism
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Wistar
  • Trace Elements / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Calmodulin
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Trace Elements
  • bcl-2-Associated X Protein
  • G(M1) Ganglioside
  • Glutamic Acid
  • Malondialdehyde
  • Oxidopamine
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Calcium