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

Joshua T.  Dearborn; Hemanth R.  Nelvagal; Nicholas R.  Rensing; Keigo  Takahashi; Stephanie M.  Hughes; Thomas Wishart; Jonathan D Cooper; Michael  Wong; Mark S.  Sands

doi:10.1038/s41598-022-15134-5

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

Joshua T. Dearborn^*, Hemanth R. Nelvagal, Nicholas R. Rensing, Keigo Takahashi, Stephanie M. Hughes, Thomas Wishart, Jonathan D Cooper, Michael Wong, Mark S. Sands ^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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 (100mg/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.

Original language	English
Article number	11286
Pages (from-to)	1 - 30
Number of pages	30
Journal	Scientific Reports
Volume	12
Issue number	1
Early online date	4 Jul 2022
DOIs	https://doi.org/10.1038/s41598-022-15134-5
Publication status	Published - 4 Jul 2022

Keywords / Materials (for Non-textual outputs)

Animals
Cannabidiol/pharmacology
Disease Models, Animal
Graft vs Host Disease/drug therapy
Mice
Neuroinflammatory Diseases
Neuronal Ceroid-Lipofuscinoses
Proteomics

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10.1038/s41598-022-15134-5

s41598-022-15134-5Final published version, 4.36 MBLicence: Creative Commons: Attribution (CC-BY)

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Dearborn, J. T., Nelvagal, H. R., Rensing, N. R., Takahashi, K., Hughes, S. M., Wishart, T., Cooper, J. D., Wong, M., & Sands , M. S. (2022). Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures. Scientific Reports, 12(1), 1 - 30. Article 11286. Advance online publication. https://doi.org/10.1038/s41598-022-15134-5

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

abstract = "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 (100mg/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. ",

keywords = "Animals, Cannabidiol/pharmacology, Disease Models, Animal, Graft vs Host Disease/drug therapy, Mice, Neuroinflammatory Diseases, Neuronal Ceroid-Lipofuscinoses, Proteomics",

author = "Dearborn, {Joshua T.} and Nelvagal, {Hemanth R.} and Rensing, {Nicholas R.} and Keigo Takahashi and Hughes, {Stephanie M.} and Thomas Wishart and Cooper, {Jonathan D} and Michael Wong and Sands, {Mark S.}",

note = "Funding Information: Funding for this research was provided by: Batten Disease Support and Research Association to JTD. NIH NS R01100779 to MSS. NIH P50 HD103525 to MW. NIH NS R21 106523 to MSS. BBSRC BBS/E/D/10002071 to TMW. Funding Information: Funding for this research was provided by: Batten Disease Support and Research Association to JTD. NIH NS R01100779 to MSS. NIH P50 HD103525 to MW. NIH NS R21 106523 to MSS. BBSRC BBS/E/D/10002071 to TMW. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Dearborn, Joshua T.

AU - Nelvagal, Hemanth R.

AU - Rensing, Nicholas R.

AU - Takahashi, Keigo

AU - Hughes, Stephanie M.

AU - Wishart, Thomas

AU - Cooper, Jonathan D

AU - Wong, Michael

AU - Sands , Mark S.

N1 - Funding Information: Funding for this research was provided by: Batten Disease Support and Research Association to JTD. NIH NS R01100779 to MSS. NIH P50 HD103525 to MW. NIH NS R21 106523 to MSS. BBSRC BBS/E/D/10002071 to TMW. Funding Information: Funding for this research was provided by: Batten Disease Support and Research Association to JTD. NIH NS R01100779 to MSS. NIH P50 HD103525 to MW. NIH NS R21 106523 to MSS. BBSRC BBS/E/D/10002071 to TMW. Publisher Copyright: © 2022, The Author(s).

PY - 2022/7/4

Y1 - 2022/7/4

N2 - 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 (100mg/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.

AB - 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 (100mg/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.

KW - Animals

KW - Cannabidiol/pharmacology

KW - Disease Models, Animal

KW - Graft vs Host Disease/drug therapy

KW - Mice

KW - Neuroinflammatory Diseases

KW - Neuronal Ceroid-Lipofuscinoses

KW - Proteomics

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DO - 10.1038/s41598-022-15134-5

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C2 - 35789177

SN - 2045-2322

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SP - 1

EP - 30

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 11286

ER -

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

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Keywords / Materials (for Non-textual outputs)

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