scholarly journals Cnr2 Is Important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

2021 ◽  
Vol 14 ◽  
Author(s):  
Luis Colón-Cruz ◽  
Roberto Rodriguez-Morales ◽  
Alexis Santana-Cruz ◽  
Juan Cantres-Velez ◽  
Aranza Torrado-Tapias ◽  
...  
Keyword(s):  
Hair Cells ◽  
Cannabinoid Receptor ◽  
Sensory Information ◽  
Endocannabinoid System ◽  
Cannabinoid Receptor 2 ◽  
Ribbon Synapses ◽  
Sensory Epithelia ◽  
Synapse Maturation ◽  
And Function

The role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong cnr2 expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Cav1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.

scholarly journals Cnr2 is important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

2020 ◽  
Author(s):  
Luis Colon-Cruz ◽  
Roberto Rodriguez-Morales ◽  
Alexis Santana-Cruz ◽  
Juan Cantres-Velez ◽  
Aranza Torrado-Tapias ◽  
...  
Keyword(s):  
Hair Cells ◽  
Cannabinoid Receptor ◽  
Sensory Information ◽  
Endocannabinoid System ◽  
Cannabinoid Receptor 2 ◽  
Ribbon Synapses ◽  
Sensory Epithelia ◽  
Synapse Maturation ◽  
And Function

ABSTRACTThe role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong cnr2 expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in zebrafish larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Cav1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the structure of the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) mediated via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.

scholarly journals Bipolar disorder and the endocannabinoid system

2019 ◽  
Vol 31 (04) ◽  
pp. 193-201 ◽  
Author(s):  
Shokouh Arjmand ◽  
Mina Behzadi ◽  
Kristi A. Kohlmeier ◽  
Shahrzad Mazhari ◽  
Abdolreza Sabahi ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Potential Role ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Cannabinoid Receptor 2 ◽  
Advantages And Disadvantages ◽  
Affective Symptoms ◽  
Probable Role ◽  
Pharmaceutical Agents

AbstractObjectiveBipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD.ResultsWe highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches.ConclusionThe probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.

scholarly journals Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer

Oncotarget ◽  
2016 ◽  
Vol 8 (18) ◽  
pp. 29668-29678 ◽  
Author(s):  
Mohamad Elbaz ◽  
Dinesh Ahirwar ◽  
Janani Ravi ◽  
Mohd W. Nasser ◽  
Ramesh K. Ganju
Keyword(s):  
Breast Cancer ◽  
Cannabinoid Receptor ◽  
Cannabinoid Receptor 2 ◽  
Igf I

scholarly journals Expression of the endocannabinoid receptors in human fascial tissue

2016 ◽  
Author(s):  
C. Fede ◽  
G. Albertin ◽  
L. Petrelli ◽  
M.M. Sfriso ◽  
C. Biz ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Trigger Points ◽  
Small Samples ◽  
Myofascial Trigger Points ◽  
Cannabinoid Receptor 2 ◽  
Culture Cells ◽  
Cb1 Cannabinoid Receptor ◽  
A Cell

Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues. Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established. Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies) and real time RT-PCR to detect the expression of CB1 and CB2. Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts. This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments. Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation.

Detailed characterization of the endocannabinoid system in human macrophages and foam cells, and anti-inflammatory role of type-2 cannabinoid receptor

2014 ◽  
Vol 233 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Valerio Chiurchiù ◽  
Mirko Lanuti ◽  
Giuseppina Catanzaro ◽  
Filomena Fezza ◽  
Cinzia Rapino ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Foam Cells ◽  
Detailed Characterization ◽  
Human Macrophages ◽  
Anti Inflammatory

scholarly journals THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amelia Dahlén ◽  
Mahdi Zarei ◽  
Adam Melgoza ◽  
Mahendra Wagle ◽  
Su Guo
Keyword(s):  
Nmda Receptor ◽  
Cannabinoid Receptor ◽  
Repetitive Behavior ◽  
Endocannabinoid System ◽  
Adult Zebrafish ◽  
Acute Effects ◽  
Cannabinoid Receptor 1 ◽  
Cannabinoid Receptor 2 ◽  
High Doses ◽  
Underlying Mechanisms

AbstractHigh doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC’s effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ‐aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model’s potential for elucidating the mechanistic relationship between Cannabis and psychosis.

scholarly journals Activity and Function of the PRMT8 Protein Arginine Methyltransferase in Neurons

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1132
Author(s):  
Rui Dong ◽  
Xuejun Li ◽  
Kwok-On Lai
Keyword(s):  
Potential Role ◽  
Neurological Diseases ◽  
Structural Features ◽  
Protein Arginine Methyltransferases ◽  
Synapse Maturation ◽  
Membrane Bound ◽  
And Function ◽  
Neuronal Functions ◽  
Mammalian Protein

Among the nine mammalian protein arginine methyltransferases (PRMTs), PRMT8 is unusual because it has restricted expression in the nervous system and is the only membrane-bound PRMT. Emerging studies have demonstrated that this enzyme plays multifaceted roles in diverse processes in neurons. Here we will summarize the unique structural features of PRMT8 and describe how it participates in various neuronal functions such as dendritic growth, synapse maturation, and synaptic plasticity. Recent evidence suggesting the potential role of PRMT8 function in neurological diseases will also be discussed.

scholarly journals Synaptic mitochondria regulate hair-cell synapse size and function

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hiu-tung C Wong ◽  
Qiuxiang Zhang ◽  
Alisha J Beirl ◽  
Ronald S Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Direct Application ◽  
Structural Protein ◽  
Ribbon Synapses ◽  
Presynaptic Function ◽  
Sensory Hair Cells ◽  
Synaptic Mitochondria ◽  
And Function ◽  
Cell Synapse

Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic-Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic-Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD+/NADH redox and downregulates ribbon size. Direct application of NAD+ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.

scholarly journals Cannabinoid Receptor 2 Alters Social Memory and Microglial Activity in an Age-Dependent Manner

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5984
Author(s):  
Joanna Agnieszka Komorowska-Müller ◽  
Tanushka Rana ◽  
Bolanle Fatimat Olabiyi ◽  
Andreas Zimmer ◽  
Anne-Caroline Schmöle
Keyword(s):  
Cannabinoid Receptor ◽  
Social Memory ◽  
Brain Aging ◽  
Endocannabinoid System ◽  
Immunohistochemical Analysis ◽  
Cellular Level ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Cannabinoid Receptor 2 ◽  
Age Related

Physiological brain aging is characterized by gradual, substantial changes in cognitive ability, accompanied by chronic activation of the neural immune system. This form of inflammation, termed inflammaging, in the central nervous system is primarily enacted through microglia, the resident immune cells. The endocannabinoid system, and particularly the cannabinoid receptor 2 (CB2R), is a major regulator of the activity of microglia and is upregulated under inflammatory conditions. Here, we elucidated the role of the CB2R in physiological brain aging. We used CB2R−/− mice of progressive ages in a behavioral test battery to assess social and spatial learning and memory. This was followed by detailed immunohistochemical analysis of microglial activity and morphology, and of the expression of pro-inflammatory cytokines in the hippocampus. CB2R deletion decreased social memory in young mice, but did not affect spatial memory. In fact, old CB2R−/− mice had a slightly improved social memory, whereas in WT mice we detected an age-related cognitive decline. On a cellular level, CB2R deletion increased lipofuscin accumulation in microglia, but not in neurons. CB2R−/− microglia showed an increase of activity markers Iba1 and CD68, and minor upregulation in tnfa and il6 expression and downregulation of ccl2 with age. This was accompanied by a change in morphology as CB2R−/− microglia had smaller somas and lower polarity, with increased branching, cell volume, and tree length. We present that CB2Rs are involved in cognition and age-induced microglial activity, but may also be important for microglial activation itself.

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