Endocannabinod Signal Dysregulation in Autism Spectrum Disorders: A Correlation Link between Inflammatory State and Neuro-Immune Alterations

被引：43

作者：

Brigida, Anna Lisa ^{[1
]}

Schultz, Stephen ^{[2
]}

Cascone, Mariana ^{[3
]}

Antonucci, Nicola ^{[4
]}

Siniscalco, Dario ^{[1
]}

机构：

[1] Univ Campania, Dept Expt Med, I-80138 Naples, Italy

[2] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Cellular & Integrat Physiol, San Antonio, TX 78229 USA

[3] Cascone Hlth & Nutr Ctr, I-80050 S Maria La Carita, Italy

[4] Biomed Ctr Autism Res & Treatment, I-70126 Bari, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2017年 / 18卷 / 07期

关键词：

endocannabinoid system; neuro-immune system; monocyte; autism; CANNABINOID RECEPTOR; VALPROIC ACID; ACETAMINOPHEN PARACETAMOL; THERAPEUTIC APPLICATIONS; DEVELOPMENTAL EXPOSURE; INTERNATIONAL UNION; SOCIAL-BEHAVIOR; CNS DISORDERS; CB1; RECEPTORS; BRAIN;

D O I：

10.3390/ijms18071425

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Several studies highlight a key involvement of endocannabinoid (EC) system in autism pathophysiology. The EC system is a complex network of lipid signaling pathways comprised of arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. In addition to autism, the EC system is also involved in several other psychiatric disorders (i.e., anxiety, major depression, bipolar disorder and schizophrenia). This system is a key regulator of metabolic and cellular pathways involved in autism, such as food intake, energy metabolism and immune system control. Early studies in autism animal models have demonstrated alterations in the brain's EC system. Autism is also characterized by immune system dysregulation. This alteration includes differential monocyte and macrophage responses, and abnormal cytokine and T cell levels. EC system dysfunction in a monocyte and macrophagic cellular model of autism has been demonstrated by showing that the mRNA and protein for CB2 receptor and EC enzymes were significantly dysregulated, further indicating the involvement of the EC system in autism-associated immunological disruptions. Taken together, these new findings offer a novel perspective in autism research and indicate that the EC system could represent a novel target option for autism pharmacotherapy.

引用

页数：13

共 117 条

[31]

Disorder American Psychiatric Association Autism Spectrum, 2013, Diagnostic and Statistical Manual of Mental Disorders DSM-5TM, V5th, P50, DOI [10.1176/appi.books.9780890425596, DOI 10.1176/APPI.BOOKS.9780890425596]

[32] Deficient adolescent social behavior following early-life inflammation is ameliorated by augmentation of anandamide signaling [J].

Doenni, V. M. ;

Gray, J. M. ;

Song, C. M. ;

Patel, S. ;

Hill, M. N. ;

Pittman, Q. J. .

BRAIN BEHAVIOR AND IMMUNITY, 2016, 58 :237-247

[33] Cannabinoids: Mechanisms and therapeutic applications in the CNS [J].

Drysdale, AJ ;

Platt, B .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (24) :2719-2732

[34] Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan [J].

Ecker, Christine ;

Bookheimer, Susan Y. ;

Murphy, Declan G. M. .

LANCET NEUROLOGY, 2015, 14 (11) :1121-1134

[35] Differential monocyte responses to TLR ligands in children with autism spectrum disorders [J].

Enstrom, Amanda M. ;

Onore, Charity E. ;

de Water, Judy A. Van ;

Ashwood, Paul .

BRAIN BEHAVIOR AND IMMUNITY, 2010, 24 (01) :64-71

[36] Altered gene expression and function of peripheral blood natural killer cells in children with autism [J].

Enstrom, Amanda M. ;

Lit, Lisa ;

Onore, Charity E. ;

Gregg, Jeff P. ;

Hansen, Robin L. ;

Pessah, Isaac N. ;

Hertz-Picciotto, Irva ;

Van de Water, Judy A. ;

Sharp, Frank R. ;

Ashwood, Paul .

BRAIN BEHAVIOR AND IMMUNITY, 2009, 23 (01) :124-133

[37] ANANDAMIDE, AN ENDOGENOUS CANNABIMIMETIC EICOSANOID, BINDS TO THE CLONED HUMAN CANNABINOID RECEPTOR AND STIMULATES RECEPTOR-MEDIATED SIGNAL-TRANSDUCTION [J].

FELDER, CC ;

BRILEY, EM ;

AXELROD, J ;

SIMPSON, JT ;

MACKIE, K ;

DEVANE, WA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (16) :7656-7660

[38] Cannabinoid-Dopamine Interaction in the Pathophysiology and Treatment of CNS Disorders [J].

Fernandez-Ruiz, Javier ;

Hernandez, Mariluz ;

Ramos, Jose A. .

CNS NEUROSCIENCE & THERAPEUTICS, 2010, 16 (03) :e72-e91

[39] Autism-Associated Neuroligin-3 Mutations Commonly Disrupt Tonic Endocannabinoid Signaling [J].

Foeldy, Csaba ;

Malenka, Robert C. ;

Suedhof, Thomas C. .

NEURON, 2013, 78 (03) :498-509

[40] Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice [J].

Frei, R. B. ;

Luschnig, P. ;

Parzmair, G. P. ;

Peinhaupt, M. ;

Schranz, S. ;

Fauland, A. ;

Wheelock, C. E. ;

Heinemann, A. ;

Sturm, E. M. .

ALLERGY, 2016, 71 (07) :944-956

← 1 2 3 4 5 6 7 8 9 10 →