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Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains

Journal Article


Abstract


  • Aims: Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson's disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat. Methods: The PD rat model was established by injecting 6-OHDA into the unilateral medial forebrain bundle; while rats were orally pre-treated with simvastatin (1 or 10 mg/kg/day), or saline for 5 days before surgery, and the same treatments for each group were continued for 3 weeks post-surgery. [3H] SR141716A binding autoradiography was adopted to investigate the alterations in CB1 receptor density in the brains. Findings: The 6-OHDA induced a remarkable downregulation of CB1 receptor density in the prefrontal cortex, caudate putamen, nucleus accumbens, cingulate cortex, hippocampus, and substantia nigra; while simvastatin (10 mg/kg/day) significantly ameliorated this downregulation in those regions. Furthermore, simvastatin (1 mg/kg/day) reversed the 6-OHDA-induced downregulation of CB1 receptors in the substantia nigra and hippocampus. Simvastatin showed minimal changes in [3H] SR141716A binding in the examined regions in sham rats, but did reveal a significant down-regulation of binding density within the striatum, prefrontal cortex and substantia nigra. Significance: Alterations in the [3H] SR141716A binding in the examined brain areas may represent the specific regions that mediate motor and cognitive dysfunctions in PD via the endocannabinoid system. Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.

Authors


  •   Mackovski, Nikolce (external author)
  •   Liao, Jinchi (external author)
  •   Weng, Ruihui (external author)
  •   Wei, Xiaobo (external author)
  •   Wang, Rui (external author)
  •   Chen, Zhaoyu (external author)
  •   Liu, Xu (external author)
  •   Yu, Yinghua
  •   Meyer, Barbara J.
  •   Xia, Ying (external author)
  •   Deng, Chao
  •   Huang, Xu-Feng
  •   Wang, Dennis (external author)

Publication Date


  • 2016

Citation


  • Mackovski, N., Liao, J., Weng, R., Wei, X., Wang, R., Chen, Z., Liu, X., Yu, Y., Meyer, B. J., Xia, Y., Deng, C., Huang, X. & Wang, Q. (2016). Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains. Life Sciences, 155 123-132.

Scopus Eid


  • 2-s2.0-84970016990

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3801

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 123

End Page


  • 132

Volume


  • 155

Place Of Publication


  • United States

Abstract


  • Aims: Cannabinoid 1(CB1) receptors are closely correlated to the dopaminergic system and involved in cognitive function. Since statins have been used to regulate the progression of Parkinson's disease (PD) via its anti-inflammation and neuroprotective effects, we asked if statins affect the CB1 receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat. Methods: The PD rat model was established by injecting 6-OHDA into the unilateral medial forebrain bundle; while rats were orally pre-treated with simvastatin (1 or 10 mg/kg/day), or saline for 5 days before surgery, and the same treatments for each group were continued for 3 weeks post-surgery. [3H] SR141716A binding autoradiography was adopted to investigate the alterations in CB1 receptor density in the brains. Findings: The 6-OHDA induced a remarkable downregulation of CB1 receptor density in the prefrontal cortex, caudate putamen, nucleus accumbens, cingulate cortex, hippocampus, and substantia nigra; while simvastatin (10 mg/kg/day) significantly ameliorated this downregulation in those regions. Furthermore, simvastatin (1 mg/kg/day) reversed the 6-OHDA-induced downregulation of CB1 receptors in the substantia nigra and hippocampus. Simvastatin showed minimal changes in [3H] SR141716A binding in the examined regions in sham rats, but did reveal a significant down-regulation of binding density within the striatum, prefrontal cortex and substantia nigra. Significance: Alterations in the [3H] SR141716A binding in the examined brain areas may represent the specific regions that mediate motor and cognitive dysfunctions in PD via the endocannabinoid system. Our data suggest a critical role of CB1 receptors in treating PD with simvastatin, and implicate CB1 receptors as a potential therapeutic target in the treatment of PD.

Authors


  •   Mackovski, Nikolce (external author)
  •   Liao, Jinchi (external author)
  •   Weng, Ruihui (external author)
  •   Wei, Xiaobo (external author)
  •   Wang, Rui (external author)
  •   Chen, Zhaoyu (external author)
  •   Liu, Xu (external author)
  •   Yu, Yinghua
  •   Meyer, Barbara J.
  •   Xia, Ying (external author)
  •   Deng, Chao
  •   Huang, Xu-Feng
  •   Wang, Dennis (external author)

Publication Date


  • 2016

Citation


  • Mackovski, N., Liao, J., Weng, R., Wei, X., Wang, R., Chen, Z., Liu, X., Yu, Y., Meyer, B. J., Xia, Y., Deng, C., Huang, X. & Wang, Q. (2016). Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains. Life Sciences, 155 123-132.

Scopus Eid


  • 2-s2.0-84970016990

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3801

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 123

End Page


  • 132

Volume


  • 155

Place Of Publication


  • United States