Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures

被引：13

作者：

Dearborn, Joshua T. ^{[1
]}

Nelvagal, Hemanth R. ^{[2
]}

Rensing, Nicholas R. ^{[3
]}

Takahashi, Keigo ^{[2
]}

Hughes, Stephanie M. ^{[4
]}

Wishart, Thomas M. ^{[5
,6
]}

Cooper, Jonathan D. ^{[2
]}

Wong, Michael ^{[3
]}

Sands, Mark S. ^{[1
,7
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, 4444 Forest Pk Blvd Ave 05536, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Univ Otago, Dept Biochem, Dunedin, New Zealand

[5] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland

[6] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh, Midlothian, Scotland

[7] Washington Univ, Sch Med, Dept Genet, 4444 Forest Pk Ave 05509, St Louis, MO 63110 USA

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

NEURONAL CEROID-LIPOFUSCINOSIS; DIRECTED GENE-THERAPY; MURINE MODEL; EPILEPSY; DEFICITS; DRUGS;

D O I：

10.1038/s41598-022-15134-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1(-/-)) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains of Cln1(-/-) mice compared to normal animals. Cln1(-/-) mice received an oral dose (100 mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency.

引用

页数：13

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