Article
Pharmacology & Pharmacy
Lesley D. O'Brien, Terry L. Smith, Giulia Donvito, Benjamin F. Cravatt, Jason Newton, Sarah Spiegel, Thomas M. Reeves, Linda L. Phillips, Aron H. Lichtman
Summary: The research reveals that DAGL-beta is not essential for TBI-induced cognitive and neurological functions, but it does have an impact on the vulnerability of male mice to TBI-induced mortality, while female mice show high survival rates regardless of DAGL-beta expression.
CANNABIS AND CANNABINOID RESEARCH
(2021)
Article
Chemistry, Analytical
Hongyi Zhang, Jiajie Luo, Zhen Qiao, Baoshuai An, Ningning Wei, Yanru Zhang
Summary: Diacylglycerol lipase (DAGL) is an important biosynthetic enzyme involved in various biological processes. However, the lack of an effective method to detect DAGL activity has hindered our understanding of its role in neurophysiological and pathological processes. In this study, a novel activatable fluorescence probe was designed to detect DAGL activity, and its application in studying changes in DAGL activity after brain injury was demonstrated.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Biochemistry & Molecular Biology
Marta Lombo, Christian Giommi, Michela Paolucci, Valentina Notarstefano, Nina Montik, Giovanni Delli Carpini, Andrea Ciavattini, Antonio Ragusa, Francesca Maradonna, Elisabetta Giorgini, Oliana Carnevali
Summary: Preeclampsia is a pregnancy-specific disease characterized by abnormal placentation, with impaired trophoblast migration. The study found a significant increase in protein levels of cannabinoid receptor 1 (CB1) in preeclamptic chorionic villi, suggesting a potential role of CB1 in the molecular effects of preeclampsia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Morteza Abyadeh, Nahid Tofigh, Saeedeh Hosseinian, Mafruha Hasan, Ardeshir Amirkhani, Matthew J. Fitzhenry, Veer Gupta, Nitin Chitranshi, Ghasem H. Salekdeh, Paul A. Haynes, Vivek Gupta, Koorosh Shahpasand, Mehdi Mirzaei
Summary: Alzheimer's disease is a complex neurodegenerative disorder that affects millions of people worldwide. Ageing is a major risk factor associated with the disease. Through gene expression data analysis, pathways and genes related to the disease were identified, providing a foundation for further research on the pathogenesis of Alzheimer's disease and potential therapeutic and diagnostic targets.
Article
Biochemistry & Molecular Biology
Berend Gagestein, Anna F. Stevens, Domenico Fazio, Bogdan Florea, Tom van der Wel, Alexander T. Bakker, Filomena Fezza, Hans den Dulk, Herman S. Overkleeft, Mauro Maccarrone, Mario van der Stelt
Summary: A study found that WOBE437 can inhibit the uptake of a specific signaling lipid in the brain, but unlike the commonly used inhibitor OMMD-1, WOBE437 actually increases the uptake of the signaling lipid in cells. Further research also identified three proteins, SCCPDH, VAT1, and FECH, that interact with WOBE437 in neuronal cells.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemical Research Methods
Barna Dudok, Ivan Soltesz
Summary: The endocannabinoid system plays a multifaceted role in the mammalian brain, primarily acting on the CB1 receptor. Despite its importance in brain function and disease, many details of eCB signaling remain unknown. Recent advances in optical microscopy methods and biosensor engineering offer new opportunities to study eCB signaling in greater detail.
JOURNAL OF NEUROSCIENCE METHODS
(2022)
Article
Psychiatry
Sarah E. Paul, Alexander S. Hatoum, Jeremy D. Fine, Emma C. Johnson, Isabella Hansen, Nicole R. Karcher, Allison L. Moreau, Erin Bondy, Yueyue Qu, Ebony B. Carter, Cynthia E. Rogers, Arpana Agrawal, Deanna M. Barch, Ryan Bogdan
Summary: This study found that prenatal cannabis exposure after maternal knowledge of pregnancy was associated with greater psychopathology during middle childhood, suggesting that cannabis use during pregnancy should be discouraged, as recommended by the Surgeon General of the United States.
Article
Multidisciplinary Sciences
Joanna Agnieszka Komorowska-Mueller, Anne-Kathrin Gellner, Kishore Aravind Ravichandran, Andras Bilkei-Gorzo, Andreas Zimmer, Valentin Stein
Summary: Cognitive function declines with age, possibly due to changes in dendritic spine stability and dynamics. Previous studies have shown that chronic low-dose THC treatment improves learning abilities in old mice, but impairs learning abilities in young mice. The underlying mechanism for this age-dependent effect is unclear. In this study, we used longitudinal 2-photon in vivo imaging to investigate how THC affects dendritic spine density and stability in 3- and 18-month-old mice. We found that THC improved spine stability and increased spine density in old mice, while transiently increasing spine turnover and destabilizing spines in young mice.
SCIENTIFIC REPORTS
(2023)
Article
Endocrinology & Metabolism
Natascha Berger, Tom van der Wel, Birgit Hirschmugl, Thomas Baernthaler, Juergen Gindlhuber, Nermeen Fawzy, Thomas Eichmann, Ruth Birner-Gruenberger, Robert Zimmermann, Mario van der Stelt, Christian Wadsack
Summary: This study found that DAGL beta is the primary active enzyme in the human placenta and plays a key role in the biosynthesis of 2-AG. Inhibition of DAGL beta activity leads to reduced levels of MAG, including 2-AG, in placental tissue.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Neurosciences
Mamoru Tanaka, Takeshi Sakaba, Takafumi Miki
Summary: The study revealed that at the hippocampal mossy fibre-CA3 interneuron synapse, there is a high occupancy probability and release probability, which are crucial determinants of short-term synaptic depression.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Chemistry, Medicinal
Giulia Bononi, Tiziano Tuccinardi, Flavio Rizzolio, Carlotta Granchi
Summary: The experimental evidence suggests a link between altered lipid metabolism and severe diseases, highlighting the potential of regulating lipid metabolism as an effective strategy against these conditions. ABHD enzymes, a diverse family of proteins, play crucial roles in lipid signaling, metabolism, and regulation, with some members involved in the endocannabinoid system. This Perspective reviews the development of ABHD inhibitors and modulators, emphasizing design strategies, structure-activity relationships, action mechanisms, and biological studies of main ABHD ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Karen Jaqueline Paredes-Ruiz, Karla Chavira-Ramos, Sonia Galvan-Arzate, Edgar Rangel-Lopez, Cimen Karasu, Isaac Tunez, Anatoly. V. V. Skalny, Tao Ke, Michael Aschner, Mario Orozco-Morales, Ana Laura Colin-Gonzalez, Abel Santamaria
Summary: Inhibition of MAGL by JZL184 has protective effects against toxic effects induced by 3-NP in brain synaptosomes. Activation of CB2R plays a major role in these effects, while CB1R has a smaller contribution. The results provide experimental evidence for the potential treatment of neurodegenerative disorders using MAGL inhibitors.
NEUROTOXICITY RESEARCH
(2023)
Review
Neurosciences
Hui-Chen Lu, Ken Mackie
Summary: The endocannabinoid system (ECS) is a neuromodulatory network involved in central nervous system development and regulating cognitive and physiological processes. It consists of endogenous cannabinoids, cannabinoid receptors, and enzymes responsible for the synthesis and degradation of endocannabinoids. The ECS is also affected by phytocannabinoids and other exogenous compounds, with implications for conditions like psychosis.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2021)
Review
Neurosciences
Jocelyne Alcaraz-Silva, Daniel Feingold, Gerardo Viana-Torre, Henning Budde, Claudio Imperatori, Sergio Machado, Eric Murillo-Rodriguez
Summary: This study reviews the evidence on the role of the endocannabinoid system in the diagnosis and treatment of depression and anxiety. The results suggest that the endocannabinoid system could be a potential strategy for mood disorders, but further research is needed.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Medicine, Research & Experimental
Sahar Rostami-Mansoor, Narges Kalantari, Tahmineh Gorgani-Firouzjaee, Salman Ghaffari, Maryam Ghasemi-Kasman
Summary: The study found a significant increase in MAGL and CB1 expression levels in the brains of Toxoplasma-infected mice, while DAGL expression remained unchanged, suggesting that T. gondii may disrupt the endocannabinoid signaling pathways, which are known to be involved in epilepsy as neurotransmitter modulators.
INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE
(2021)
Article
Neurosciences
Yurie Rai, Takaki Watanabe, Kyoko Matsuyama, Kenji Sakimura, Naofumi Uesaka, Masanobu Kano
Summary: Research indicates that the expression levels of phospholipase C I33 (PLC I33) can impact the extent of climbing fiber (CF) innervation in Purkinje cells in the cerebellum of mice, consequently affecting the elimination of CF synapses.
Review
Neurosciences
Yuki Sugaya, Masanobu Kano
Summary: Research on endocannabinoid signaling has provided valuable insights into the control of neural circuit excitability in both healthy and diseased states. Recent advancements in the development of cannabinoid sensors have allowed for a better understanding of the activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, this research has opened up possibilities for the clinical use of cannabidiol in the treatment of refractory epilepsy.
FRONTIERS IN NEURAL CIRCUITS
(2022)
Article
Biochemistry & Molecular Biology
Shoji Tanaka, Naotoshi Sugimoto, Takako Ohno-Shosaku, Sachiko Madokoro, Pleiades Tiharu Inaoka, Toshiaki Yamazaki
Summary: This study examined the effects of theobromine on skeletal muscles in rats. The results showed that long-term consumption of a 0.05% theobromine diet had no significant effect on muscle hypertrophy and contractile properties. However, theobromine had similar effects to clenbuterol in upregulating the expression of myosin heavy chain 2x and myogenic differentiation 1.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Multidisciplinary Sciences
Eri Tabuchi, Takeshi Sakaba, Yuki Hashimotodani
Summary: Recent evidence suggests that glutamate and GABA can be coreleased from the same presynaptic terminals in certain adult brain regions, such as the SuM-DG pathway. The LTP of glutamatergic transmission selectively increases excitatory drive, contributing to network activity in the DG region.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Behavioral Sciences
Yui Kikuchi, Mitsugu Yoneda, Kyoko Nishikawa, Tsukika Noda, Honoka Hasegawa, Tomoaki Fujisaku, Takako Ohno-Shosaku
Summary: The beneficial effects of environmental enrichment on the central nervous system have been demonstrated, but its effects on reward-based motor learning have been limitedly studied. This study found that mice raised in an enriched environment showed behavioral differences in operant tasks compared to control mice, including delayed shift from exploration to exploitation, higher lose-shift performance, and more frequent pressing of multiple levers.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Cell Biology
Maria Harbers, Harumi Nakao, Takaki Watanabe, Kyoko Matsuyama, Shoichi Tohyama, Kazuki Nakao, Yasushi Kishimoto, Masanobu Kano, Atsu Aiba
Summary: mGluR1 and mGluR5 show complementary distributions in the central nervous system. The study on mGluR5-rescue mice suggests that mGluR5 functions comparably to mGluR1 in cerebellar Purkinje cells.
Article
Multidisciplinary Sciences
Chiaki Itami, Naofumi Uesaka, Jui-Yen Huang, Hui-Chen Lu, Kenji Sakimura, Masanobu Kano, Fumitaka Kimura
Summary: Columnar structure is a fundamental feature of the cerebral cortex, and endocannabinoid signaling through CB1R plays a crucial role in shaping columnar axonal projection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Tetsuo Ota, Yui Kikuchi, Ikumi Amiya, Takako Ohno-Shosaku, Yasuharu Koike, Mitsugu Yoneda
Summary: The neural circuits connecting the cerebellum and the cerebral cortex play crucial roles in motor and cognitive functions. Assessing the function of the cerebellum is clinically important for patients with motor and cognitive dysfunctions. This study investigated the evaluation of motor learning process in a simple loading task using a space interface device for artificial reality. The results showed that repeated training in the loading task improved the time constant and movement patterns, and these effects were maintained into the next day. Training with eyes closed also yielded positive results, indicating that proprioceptive information is sufficient for performance improvement.
EXPERIMENTAL BRAIN RESEARCH
(2022)
Article
Cell Biology
Himawari Hirai, Takeshi Sakaba, Yuki Hashimotodani
Summary: This study demonstrates the presence of associative long-term potentiation at the synapses from the hypothalamic supramammillary nucleus to the dentate granule cells, indicating the involvement of Hebbian plasticity in regulating this subcortical input.
Article
Neurosciences
Mahendra Singh, Kiran Sapkota, Kenji Sakimura, Masanobu Kano, Rita M. Cowell, Linda Overstreet-Wadiche, John J. Hablitz, Kazu Nakazawa
Summary: Hypofunction of the NMDAR receptor during brain development may contribute to the onset of schizophrenia in young adults. The cellular targets of NMDAR hypofunction include corticolimbic fast-spiking interneurons. However, the functional alterations in PV-positive FS interneurons following NMDAR hypofunction are not well understood.
Article
Neurosciences
Yuto Okuno, Kazuto Sakoori, Kyoko Matsuyama, Miwako Yamasaki, Masahiko Watanabe, Kouichi Hashimoto, Takaki Watanabe, Masanobu Kano
Summary: Functionally mature neural circuits are shaped by eliminating redundant synapses during postnatal development. A synapse organizer, PTPd, is necessary for CF synapse formation and establishing CF to PC synaptic wiring. PTPd KO mice showed impaired CF translocation and synaptic transmission in Aldoc (-) PCs. The lack of PTPd also caused a mild impairment of motor performance.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Ryota Fukaya, Himawari Hirai, Hirokazu Sakamoto, Yuki Hashimotodani, Kenzo Hirose, Takeshi Sakaba
Summary: This study reveals the important role of presynaptic long-term potentiation (LTP) in learning and memory. By using optogenetic tools and direct presynaptic patch-clamp recordings, the researchers found that LTP induction increased the release probability of synaptic vesicles without changing the number of release-ready vesicles. Enhanced synaptic vesicle replenishment and increased numbers of Munc13-1 and RIM1 molecules within active zones were also observed. These findings suggest that dynamic changes in active zone components may contribute to the increased fusion competence and synaptic vesicle replenishment during LTP.
Article
Multidisciplinary Sciences
Kisho Obi-Nagata, Norimitsu Suzuki, Ryuhei Miyake, Matthew L. MacDonald, Kenneth N. Fish, Katsuya Ozawa, Kenichiro Nagahama, Tsukasa Okimura, Shoji Tanaka, Masanobu Kano, Yugo Fukazawa, Robert A. Sweet, Akiko Hayashi-Takagi
Summary: By studying mouse models with knockdown of the SETD1A and DISC1 genes, it was found that XL synapses can lead to excessive neuronal firing and impair working memory. This finding provides new evidence for understanding the synaptic pathology of psychiatric disorders.
Article
Neurosciences
Takako Ohno-Shosaku, Mitsugu Yoneda, Takashi Maejima, Mohan Wang, Yui Kikuchi, Kaito Onodera, Yuji Kanazawa, Chitoshi Takayama, Michihiro Mieda
Summary: This study examined the role of the thalamic reticular nucleus (TRN) in reward-based learning of action sequences. The findings suggest that the TRN plays an important role in action sequence learning, while not affecting simple operant learning.
Article
Biochemical Research Methods
Masayuki Sakamoto, Masatoshi Inoue, Atsuya Takeuchi, Shigetaka Kobari, Tatsushi Yokoyama, Shin-ichiro Horigane, Sayaka Takemoto-Kimura, Manabu Abe, Kenji Sakimura, Masanobu Kano, Kazuo Kitamura, Hajime Fujii, Haruhiko Bito
Summary: This study generates a transgenic mouse line that expresses a highly sensitive green GECI in specific neuronal populations. In vivo imaging reveals calcium transients in both excitatory and inhibitory neurons, providing a tool for investigating neuronal activity with enhanced resolution.
CELL REPORTS METHODS
(2022)