Biology subjects

Meiri, D.

Publications and source records attributed to Meiri, D..

4 recordsLinked to original sources

bioRxiv2025

Circadian-Related Dynamics of the Endocannabinoid System in Male Mouse Brain

Endocannabinoids (eCBs) and related lipids play crucial roles in brain function, including the regulation of circadian rhythms and sleep. To comprehensively map these molecules, we employed liquid chromatography high-resolution tandem mass spectrometry (LC/HRMS/MS) to quantify 78 lipids across 14 families in seven brain areas of male mice at four time points throughout the day (every six hours), and during sleep initiation. We found that most eCBs from the fatty acids (FAs) family, particularly arachidonic acid (AA), were highly abundant in the mouse brain in all brain areas and during the circadian rhythm. High eCBs abundance was shown in deeper brain areas, while temporal differences using the Cosinor analysis revealed 26 eCBs behaving in a circadian rhythm response, with linolenic acid (LnA) being the only lipid to show rhythmicity across all brain areas. Sleep initiation (ZT1) was associated with increased N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) activity and N-acylethanolamide (NAE) levels in the cortex and hippocampus, while wake extension (WEx) altered 2-monoacylglycerol (2-MAG) metabolism and increased cannabinoid receptor 1 (CB1) expression. These findings provide a detailed lipidomic map of eCBs and related lipids in the male mouse brain, highlighting their area-specific distribution, circadian regulation, and involvement in sleep/wake transitions. Given the link between sleep disruption and neurodegeneration, future studies should investigate whether the observed eCB dysregulation contributes to sleep disturbances in these conditions, and if targeting these pathways offers novel therapeutic strategies. Significant StatementThis comprehensive study provides a high-dimensional map of eCBs and related lipids in the male mouse brain, revealing intricate spatial and temporal dynamics highlighting the role of these lipids in regulating fundamental physiological processes such as circadian rhythm and sleep.

neuroscience↗

bioRxiv2025

Effects of Drought on Inflorescence Yield, and Secondary Metabolites in Cannabis sativa L.

O_LIThe use of medical products derived from Cannabis sativa L. has increased significantly in recent years. While drought is known to negatively affect the yields of many crops, growers often recommend controlled periods of drought for cannabis cultivation to increase concentrations of secondary metabolites. This is especially pertinent when considering the relationship between medicinal effects and the secondary-metabolite profile. C_LIO_LIWe examined the effects of tightly controlled drought treatments on biochemical (111 phytocannabinoids and 132 terpenoids), physiological, and anatomical responses of three Type-I chemotype cultivars, specifically the THCA-dominant cultivars Odem, MVA, and 187. C_LIO_LIOur results revealed strong correlations between inflorescence and phytocannabinoid yields, on the one hand, and cumulative transpiration on the other (0.96 < r2 < 0.99). Drought treatment reduced canopy conductance, with inflorescence weight decreasing by 40% and total fresh weight decreasing by 48%. The concentrations of the major phytocannabinoids, THCA and CBGA, decreased over increasing levels of drought stress (by 26% and 61%, respectively). Interestingly, terpene concentrations showed greater stress-induced variation, and that variation was genotype-dependent. C_LIO_LIOur findings suggest that the decreases in inflorescence weight and concentrations of major phytocannabinoids under drought conditions are mainly due to a lack of biochemical-production processes, as opposed to metabolic degradation. C_LI

plant biology↗

bioRxiv2023

Cannabinoid Combination Targets NOTCH1-Mutated T-ALL Through the Integrated Stress Response Pathway

In T-cell acute lymphoblastic leukemia (T-ALL) more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation. We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, Cannabidiol (CBD) and Cannabidivarin (CBDV); whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study. We demonstrated that these cannabinoids act through Cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca2+. This is followed by increased mRNA and protein expression of ATF4, CHOP and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis. Treatment with the three isolated molecules resulted in reduced tumor size and weight in-vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treating NOTCH1-mutated diseases and cancers such as T-ALL.

cancer biology↗

bioRxiv2021

Bioelectricity generation from live marine photosynthetic macroalgae

Conversion of solar energy into electrical current by photosynthetic organisms has the potential to produce clean energy. Previously reported bio-photoelectrochemical cells (BPECs) have utilized unicellular photosynthetic microorganisms. In this study, we describe for the first time BPECs that utilize intact live marine macroalgae (seaweeds) in natural seawater or saline buffer or natural seawater. The BPECs produce electrical currents from of >50mA/cm2, from both light-dependent (photosynthesis) and light independent processes. These values are significantly greater than the current densities that have been reported for single-cell microorganisms. The photocurrent is inhibited by the Photosystem II inhibitor DCMU, indicating that the source of light-driven electrons is from water oxidation via NADPH and other reduced molecules. We show here that intact seaweed cultures can be used in a large-scale BPEC containing seawater that produces bias-free photocurrent. The ability to produce bioelectricity from intact seaweeds may pave the way to future development of a low-cost energy technology using BPECs.

bioengineering↗