Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
13 10 2021
13 10 2021
Historique:
received:
30
12
2020
accepted:
04
08
2021
revised:
16
07
2021
entrez:
14
10
2021
pubmed:
15
10
2021
medline:
31
10
2021
Statut:
epublish
Résumé
Autism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestation. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field. In this study, we investigate the behavioral and biochemical effects of long-term oral treatment with CBD-enriched medical cannabis oil in a human mutation-based Shank3 mouse model of ASD. Our findings show that this treatment alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, we were able to uncover the involvement of CB1 receptor (CB1R) signaling in the Avidekel oil mechanism, alongside a mitigation of cerebrospinal fluid (CSF) glutamate concentrations. Subsequently, RNA sequencing (RNA seq) of cerebellar brain samples revealed changes in mRNA expression of several neurotransmission-related genes post-treatment. Finally, our results question the relevancy of CBD enrichment of medical cannabis for treating the core symptoms of ASD, and emphasize the importance of the THC component for alleviating deficits in repetitive and social behaviors in ASD.
Identifiants
pubmed: 34645786
doi: 10.1038/s41398-021-01612-3
pii: 10.1038/s41398-021-01612-3
pmc: PMC8514476
doi:
Substances chimiques
Medical Marijuana
0
Microfilament Proteins
0
Nerve Tissue Proteins
0
Shank3 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
524Informations de copyright
© 2021. The Author(s).
Références
Curr Med Chem. 2015 Feb 09;22(15):1850 - 59
pubmed: 25666800
Int J Mol Sci. 2017 Sep 07;18(9):
pubmed: 28880200
Sci Rep. 2019 Jan 17;9(1):200
pubmed: 30655581
J Intellect Disabil Res. 2008 Oct;52(10):819-29
pubmed: 18444989
Neural Plast. 2011;2011:286073
pubmed: 21766040
J Autism Dev Disord. 2019 Mar;49(3):1284-1288
pubmed: 30382443
Trends Plant Sci. 2020 Oct;25(10):976-984
pubmed: 32417167
Neurobiol Aging. 2018 Jan;61:177-186
pubmed: 29107185
Prog Neurobiol. 1991;37(1):1-82
pubmed: 1947175
Neuropsychopharmacology. 2011 May;36(6):1219-26
pubmed: 21307846
Behav Brain Res. 2016 Mar 1;300:135-42
pubmed: 26518331
J Neuroendocrinol. 2008 May;20 Suppl 1:75-81
pubmed: 18426504
Nat Neurosci. 2016 Apr 26;19(6):647-655
pubmed: 29323671
J Biol Chem. 2011 Oct 7;286(40):34839-50
pubmed: 21795692
J Clin Invest. 2020 Apr 1;130(4):1728-1742
pubmed: 31874107
Synapse. 2008 Jul;62(7):501-7
pubmed: 18435417
J Autism Dev Disord. 1986 Mar;16(1):23-9
pubmed: 3957856
Bioinformatics. 2002;18 Suppl 1:S96-104
pubmed: 12169536
Trends Pharmacol Sci. 2007 Feb;28(2):83-92
pubmed: 17222464
Eur Arch Psychiatry Clin Neurosci. 2013 Aug;263(5):379-84
pubmed: 22986449
Neuropsychopharmacology. 2018 Jan;43(1):21-33
pubmed: 28685756
Br J Pharmacol. 2008 Jan;153(2):199-215
pubmed: 17828291
Pharmacol Biochem Behav. 2008 Nov;91(1):84-90
pubmed: 18640150
Nat Rev Neurosci. 2017 Mar;18(3):147-157
pubmed: 28179641
Soc Cogn Affect Neurosci. 2014 Sep;9(9):1341-5
pubmed: 23988761
Eur J Neurosci. 2010 Feb;31(3):544-55
pubmed: 20105240
Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E7049-E7058
pubmed: 27663735
Genome Biol. 2014;15(12):550
pubmed: 25516281
Eur J Pharmacol. 1998 Jul 17;353(1):23-31
pubmed: 9721036
Nature. 2011 Apr 28;472(7344):437-42
pubmed: 21423165
Br J Psychiatry. 2011 Jun;198(6):442-7
pubmed: 21628706
Neurosci Res. 2015 Nov;100:1-5
pubmed: 26116891
Psychopharmacology (Berl). 2020 Jan;237(1):199-208
pubmed: 31595334
Lancet. 2014 Mar 8;383(9920):896-910
pubmed: 24074734
J Psychopharmacol. 2010 May;24(5):767-77
pubmed: 19406854
Neurochem Res. 2005 Aug;30(8):1037-43
pubmed: 16258853
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Neuroscience. 1997 Mar;77(2):299-318
pubmed: 9472392
Neurotherapeutics. 2015 Oct;12(4):825-36
pubmed: 26341731
ACS Nano. 2017 Nov 28;11(11):10883-10893
pubmed: 28960957
Mol Autism. 2015 Sep 04;6:50
pubmed: 26347127
Curr Protoc Neurosci. 2017 Jul 5;80:9.59.1-9.59.10
pubmed: 28678398
Neurology. 2014 Apr 29;82(17):1556-63
pubmed: 24778283
Pharmacol Biochem Behav. 2006 Sep;85(1):243-52
pubmed: 16996123
Pharmacol Biochem Behav. 2002 Nov;73(4):911-9
pubmed: 12213538
Pharmacol Ther. 2015 Apr;148:1-16
pubmed: 25460036
Eur J Med Chem. 2020 Apr 15;192:112163
pubmed: 32109623
Neuropharmacology. 2016 Apr;103:16-26
pubmed: 26711860
Am J Med Genet. 2001 Apr 15;100(1):30-6
pubmed: 11337745
Pharmaceuticals (Basel). 2018 Jun 04;11(2):
pubmed: 29867038
Front Hum Neurosci. 2010 Dec 21;4:224
pubmed: 21191475
Eur Child Adolesc Psychiatry. 2012 Apr;21(4):237-8
pubmed: 22350104
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:245-253
pubmed: 30261217
Neuron. 2014 Aug 20;83(4):894-905
pubmed: 25088363
Glia. 2019 Nov;67(11):2125-2141
pubmed: 31058364
Ann Neurol. 2005 Jan;57(1):67-81
pubmed: 15546155
Nat Rev Neurosci. 2015 Aug;16(8):469-86
pubmed: 26189694
Neurosci Biobehav Rev. 2021 Feb;121:128-143
pubmed: 33358985
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Neuron. 2016 Jan 6;89(1):147-62
pubmed: 26687841
J Clin Pharm Ther. 2014 Oct;39(5):564-6
pubmed: 24845114
Pharmacol Biochem Behav. 2012 Feb;100(4):841-9
pubmed: 21756930
Behav Brain Res. 2010 Jan 20;206(2):245-53
pubmed: 19766676
Mol Aspects Med. 2012 Oct-Dec;33(5-6):562-78
pubmed: 22504060
Pharmacol Rev. 2013 Mar 19;65(2):849-71
pubmed: 23512546
Sci Rep. 2017 Mar 21;7(1):258
pubmed: 28325891
Transl Psychiatry. 2018 May 25;8(1):106
pubmed: 29802263
Am J Drug Alcohol Abuse. 2019;45(6):551-562
pubmed: 30864864
Neuropsychopharmacology. 2017 Nov;42(12):2456-2465
pubmed: 27869141
Nat Med. 2017 Jun;23(6):782-787
pubmed: 28481360
Nano Lett. 2019 Jun 12;19(6):3422-3431
pubmed: 30761901
Nature. 2011 Jul 27;477(7363):171-8
pubmed: 21796121
Methods Mol Biol. 2019;2011:493-510
pubmed: 31273718
Int J Mol Cell Med. 2017 Summer;6(3):148-155
pubmed: 29682486
Curr Biol. 2020 Jan 6;30(1):R8-R9
pubmed: 31910378
Addict Biol. 2008 Sep;13(3-4):345-57
pubmed: 18782382
Seizure. 2016 Feb;35:41-4
pubmed: 26800377
Nat Genet. 2007 Jan;39(1):25-7
pubmed: 17173049
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:90-96
pubmed: 30171992
PLoS One. 2012;7(7):e38786
pubmed: 22848344
Mol Autism. 2020 Aug 17;11(1):65
pubmed: 32807217
Cell. 2020 Feb 6;180(3):568-584.e23
pubmed: 31981491
Rambam Maimonides Med J. 2020 Jan 30;11(1):
pubmed: 32017680
Int J Mol Sci. 2018 Jan 22;19(1):
pubmed: 29361800
Front Neurol. 2019 Oct 31;10:1145
pubmed: 31736860
Autism Res. 2013 Feb;6(1):1-10
pubmed: 23166003
Genes Brain Behav. 2003 Oct;2(5):255-67
pubmed: 14606691
Eur Arch Psychiatry Clin Neurosci. 2009 Oct;259(7):371-82
pubmed: 19588184