Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice

Spencer, Jarrah R.; Darbyshire, Keturah M.E.; Boucher, Aurélie A.; Kashem, Mohammed A.; Long, Leonora E.; McGregor, Iain S.; Karl, Tim; Arnold, Jonathon C.

doi:10.3389/fncel.2013.00015

Cited by 32 publications

(22 citation statements)

References 100 publications

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“…In fact, chronic administration of THC impairs spatial memory and reduces a learning-related transcription factor (zif268) expression in the mouse forebrain [83]. This is consistent with the significant reduction in the number of synapses per unit volume (44%) as well as a reduction in the dendritic length of CA3 pyramidal neurons, as observed in rats receiving high doses of THC (10 to 60 mg/ kg), during a long period of treatment (90 days) [84].…”

Section: The Opposite Effectsupporting

confidence: 66%

Cannabinoids in Neuroinflammation, Oxidative Stress and Neuro Excitotoxicity

M¹

2015

Pharm Anal Acta

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Research on cannabinoids has been growing significantly in the last five years. More than fifty percent of this research corresponds to "cannabinoids and brain", particularly about neurodegeneration. In this sense, there is evidence reporting that specific phyto cannabinoids show some specific action on each one of main pathogenic mechanisms involved in neurodegeneration such as oxidative stress, neuroinflammation and excitotoxicity. However, by using the same targets, cannabinoids may also induce the opposite effects, this is, excitotoxicity and inflammation. In fact, both tetrahydro cannabinol and cannabidiol activate cannabinoid receptors, but they also may act as antagonists of those receptors. It seems to be a dose-dependent issue; nonetheless, as reviewed in this paper, many other factors such as timing, type of cell and its state of activity even the activation of different, noncannabinoid receptorsseem to have a role related to those unexpected antagonic effects.

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Section: The Opposite Effectsupporting

confidence: 66%

Cannabinoids in Neuroinflammation, Oxidative Stress and Neuro Excitotoxicity

M¹

2015

Pharm Anal Acta

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“…Thus, ErbB4 and CB1 might interact in the substantia nigra and thereby regulate the hyper-locomotor phenotype of Nrg1 mutant mice. Nrg1 also conferred opposing effects of THC on 5-HT2A receptor expression in the insular cortex and NMDA receptor binding was selectively increased in the hippocampus and cingulate cortex of Nrg1 HET mice (Long et al, 2013) (for a better mechanistic understanding of Nrg1 -THC interaction on NMDA receptor expression in the hippocampus see Spencer et al, 2013). …”

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confidence: 99%

What does a mouse tell us about neuregulin 1—cannabis interactions?

Karl¹,

Arnold²

2013

Front. Cell. Neurosci.

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The link between cannabis and psychosis has been debated although there is substantial epidemiological evidence showing that cannabis increases the risk of psychosis. It has been hypothesized that schizophrenia patients carrying particular risk genes might be more sensitive to the psychosis-inducing effects of cannabis than other patients and healthy test subjects. Here we review the effects of cannabinoids on a mutant mouse model for the schizophrenia candidate gene neuregulin 1 (Nrg1). The studies suggest a complex interaction between cannabis and Nrg1: the neuro-behavioral effects of cannabinoids were different in Nrg1 mutant and control mice and depended on exposure time, sex, and age of test animals. This research provides the first evidence of complex cannabis-Nrg1 interactions suggesting Nrg1 as a prime target for future clinical investigations. Furthermore, it highlights that animal model research can broaden our understanding of the complex multi-factorial etiology of schizophrenia. Finally, the findings are important to preventive psychiatry: if the genes that confer genetic vulnerability to cannabis-induced psychosis were identified patients at-high risk could be forewarned of the potential dangers of cannabis abuse.

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“…This is consistent with the idea that neuroinflammatory processes are implicated in the pathophysiology of schizophrenia and other psychiatric conditions. Additionally, NAPE‐PLD is upregulated in adolescent Nrg1 HET mice treated with ∆9‐THC, compared to a vehicle‐treated group, suggesting a possible mechanism of ∆9‐THC in regulation of anandamide levels. Initially, it was believed that phytocannabinoids like ∆9‐THC only has CB1/CB2 agonist properties, but current studies have shown the effects of these compounds in enzymatic process, and with the analyses we reported a role of ∆9‐THC in NAPE‐PLD (Figure ).…”

Section: Schizophrenia and Endocannabinoid Systemmentioning

confidence: 96%

“…Although some studies applying genetic, image, and behavioral task methodologies, as described above (see Schizophrenia and Endocannabinoid System Section), have pinpointed a role of this system in the pathophysiology of schizophrenia, few proteomic investigations have been carried out with the same goals in mind. In the case of preclinical studies, hippocampal samples from the neuregulin 1 transmembrane heterozygous (Nrg1 HET) mouse—a model of schizophrenia—was used in a proteome profiling analysis . These animals and their wild‐type (WT) littermates were treated with ∆9‐THC, and the proteome analyses demonstrated that Nrg1 HET mice presented changes in the abundance of proteins involved in several biological processes (Table ).…”

Section: Schizophrenia and Endocannabinoid Systemmentioning

confidence: 99%

Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

et al. 2018

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Interest in the modulation of endocannabinoid signaling has increased since the discovery of receptors for compounds of Cannabis sativa. Endocannabinoids are crucial neuromodulators of many brain functions and changes in the ligands and their receptors have been associated with psychiatric disorders, such as schizophrenia. Genetic, neuroimaging, and behavioral studies have reinforced the role of endocannabinoids in the pathobiology of schizophrenia. However, molecular pathways and biological processes involved in cannabinoid effects are not totally understood. Additionally, the endocannabinoid signaling network with other non-cannabinoid targets, and the effects of phytocannabinoids increase the complexity to understand their role in schizophrenia and homeostasis conditions. Thus, proteomic studies can provide evidence about the involvement of cannabinoid receptors, as well as the metabolic and synthetic enzymes of the endocannabinoids in these disorders. Additionally, quantification of endocannabinoids in the blood serum or cerebrospinal fluid can be a useful approach to identify new biomarkers in schizophrenia, and lipidomic techniques can be used to quantify these compounds. Herein, the authors review proteomic and lipidomic studies that have been used for analysis of the endocannabinoid system in healthy and schizophrenia function. The findings may contribute to understand the involvement of endocannabinoids in the brain and in the neurobiological basis of schizophrenia.

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Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice

Cited by 32 publications

References 100 publications

Cannabinoids in Neuroinflammation, Oxidative Stress and Neuro Excitotoxicity

Cannabinoids in Neuroinflammation, Oxidative Stress and Neuro Excitotoxicity

What does a mouse tell us about neuregulin 1—cannabis interactions?

Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

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