Acute cannabidiol treatment enhances social interaction in adult male mice

Advances in Drug and Alcohol Research, Год журнала: 2023, Номер 3

Опубликована: Май 10, 2023

Cannabidiol (CBD) is a non-intoxicating phytochemical from Cannabis sativa that increasingly used to manage pain. The potential for CBD ameliorate dimensional behavior symptoms occurring in multiple psychiatric disorders was suggested, including social interaction impairments. To test this hypothesis, adult male BTBRT+Itpr3tf/J (BTBR) mice, model of idiopathic autism exhibiting preference deficits and restrictive repetitive behaviors, were acutely treated with vehicle or 0.1, 1, 10 mg/kg CBD. Social assessed 50 min after treatment, followed by novelty at 60 min, marble burying 75 dominance 120 min. (10 mg/kg) enhanced BTBR but not preference, dominance, serum levels = 29 ± 11 ng/mg 3 h post-injection. Next, acute compared treatment serotonin transporter (SERT) knock-out since SERT deficiency an risk factor, their wildtype background strain controls C57BL/6J mice. generally attenuated yet neither nor affected. These findings show as little purified can enhance mice are otherwise socially deficient.

Язык: Английский

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Neurophysiology of corneal neuropathic pain and emerging pharmacotherapeutics

Journal of Neuroscience Research, Год журнала: 2023, Номер 102(1)

Опубликована: Дек. 28, 2023

Abstract The altered activity generated by corneal neuronal injury can result in morphological and physiological changes the architecture of synaptic connections nervous system. These alter sensitivity neurons (both second‐order higher‐order projection) projecting pain signals. A complex process involving different cell types, molecules, nerves, dendritic cells, neurokines, neuropeptides, axon guidance molecules causes a high level sensory rearrangement, which is germane to all phases pathomechanism neuropathic pain. Immune cells migrating region nerve assist generation secreting neurokines that ensure depolarization. Furthermore, excitability central pathway perpetuated local activation microglia trigeminal ganglion alterations descending inhibitory modulation for arriving from Corneal may be facilitated dysfunctional structures somatosensory system due lesion, synaptogenesis, or genetic abnormality. Understanding these important pathways will provide novel therapeutic insight.

Язык: Английский

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In silico analyses of the involvement of GPR55, CB1R and TRPV1: response to THC, contribution to temporal lobe epilepsy, structural modeling and updated evolution

Frontiers in Neuroinformatics, Год журнала: 2024, Номер 18

Опубликована: Фев. 7, 2024

Introduction The endocannabinoid (eCB) system is named after the discovery that endogenous cannabinoids bind to same receptors as phytochemical compounds found in Cannabis. While include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), exogenous phytocannabinoids Δ-9 tetrahydrocannabinol (THC) cannabidiol (CBD). These finely tune neurotransmission following synapse activation, via retrograde signaling activates cannabinoid receptor 1 (CB1R) and/or transient potential cation channel subfamily V member (TRPV1). Recently, eCB has been linked several neurological diseases, such neuro-ocular abnormalities, pain insensitivity, migraine, epilepsy, addiction neurodevelopmental disorders. In current study, we aim to: (i) highlight a link between disorders, (ii) assess if THC exposure alters expression of eCB-related genes, (iii) identify evolutionary-conserved residues CB1R or TRPV1 light their function. Methods To address this, used bioinformatic approaches, transcriptomic (Gene Expression Omnibus), protein–protein (STRING), phylogenic (BLASTP, MEGA) structural (Phyre2, AutoDock, Vina, PyMol) analyzes. Results Using RNA sequencing datasets, did not observe any dysregulation transcripts major depressive bipolar disorder schizophrenia anterior cingulate cortex, nucleus accumbens dorsolateral striatum. Following vivo adolescent mice, GPR55 was significantly upregulated neurons from ventral tegmental area, while other involved were affected by exposure. Our results also suggest likely induces neuroinflammation vitro application on mice microglia. Significant downregulation TPRV1 occurred hippocampi which model temporal lobe epilepsy induced, confirming previous observations. addition, dysregulations observed both epileptic humans, included neuronal death. When scanning known interactions for (n = 12), branching neurophysiology, including proteins dopaminergic system. protein analyzes revealed forms clade with CB2R, distinct related paralogues sphingosine-1-phosphate, receptors, lysophosphatidic acid melanocortin receptors. As expected, conserved identified, are crucial anandamide-binding pocket seems have appeared later evolution. Similar TRPV1, activation. Conclusion study exposure, downregulated epilepsy. Caution advised when interpreting present results, employed secondary Common ancestors diverged jawless vertebrates during late Ordovician, 450 million years ago. Conserved mediate functions.

Язык: Английский

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TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.

PubMed, Год журнала: 2024, Номер 27(3), С. 270 - 278

Опубликована: Янв. 1, 2024

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases death in Western cultures. Ischemia occurs when blood circulation is reduced tissues. Reperfusion, although commanded to return oxygen ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive species (ROS), stimulating inflammatory organs, endoplasmic reticulum stress, expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute ischemia/reperfusion; therefore, targeting different may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs TRP family ion channels, detects a broad range chemicals, promotes transduction noxious stimuli, e.g., methylglyoxal, ROS, acrolein effects attributed channel's sensitivity intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia ischemia associated with oxidative activates TRPA1 channel. This review describes role its related mechanisms that ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web Sciences, Google Scholar electronic databases, up end August 2023. Based on evidence presented here, have protective deteriorative functions during ischemia/reperfusion process. Its function depends activation level, region, extent lesions, duration ischemia.

Язык: Английский

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A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides

Nucleic Acids Research, Год журнала: 2024, Номер 52(9), С. 4784 - 4798

Опубликована: Апрель 16, 2024

Abstract Antisense oligonucleotide (ASO) therapy is a novel therapeutic approach in which ASO specifically binds target mRNA, resulting mRNA degradation; however, cellular uptake of ASOs remains critically low, warranting improvement. Transient receptor potential canonical (TRPC) channels regulate Ca2+ influx and are activated upon stimulation by phospholipase C-generated diacylglycerol. Herein, we report that TRPC3/C6/C7 activator, L687, can induce uptake. L687-induced was enhanced dose- incubation-time-dependent manner. L687 the knockdown activity various both vitro vivo. Notably, suppression TRPC3/C6 specific siRNAs reduced A549 cells. Application BAPTA-AM, chelator, SKF96365, inhibitor, suppressed via TRPC3/C6, uptake, thereby suggesting critical for L687-mediated increased also induced dextran indicating endocytosis. Adding to resulted endosome accumulation; endosomal membrane disruptor UNC7938 facilitated escape activity. We discovered new function TRPC activators regarding trafficking Our findings provide an opportunity formulate innovative drug delivery system development ASO.

Язык: Английский

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