Article
Neurosciences
Eva Maria Meier Carlsen, Sarah Falk, Urszula Skupio, Laurie Robin, Antonio C. Pagano Zottola, Giovanni Marsicano, Jean-Francois Perrier
Summary: The study demonstrates that cannabinoids reduce tremor associated with motor disorders by acting on cannabinoid receptors on astrocytes in the spinal cord, ultimately inhibiting excitatory synaptic transmission and decreasing tremor.
NATURE NEUROSCIENCE
(2021)
Article
Cell Biology
Saja Baraghithy, Yael Soae, Dekel Assaf, Liad Hinden, Shiran Udi, Adi Drori, Yankel Gabet, Joseph Tam
Summary: Targeting CB1R in RPTCs can protect bone density and remodeling, preventing diabetes-induced bone loss, which is related to its modulation of EPO synthesis.
Article
Pharmacology & Pharmacy
Jamie J. Manning, Gabriel Rawcliffe, David B. Finlay, Michelle Glass
Summary: This study investigated the impact of phosphorylation modifications in a specific sequence of the CB1 receptor C-terminus on the translocation of Arrestin-2 and Arrestin-3. The results showed that these modifications partially contributed to the translocation of Arrestin, but complete inhibition was only achieved when all phosphorylation sites were mutated. Additionally, the dissociation of G proteins was also impaired proportionally to the extent of Arrestin translocation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Alex Straiker, Michaela Dvorakova, Taryn Bosquez-Berger, Jaroslav Blahos, Ken Mackie
Summary: Autaptic hippocampal neurons are a simple model for studying neurotransmission and cannabinoid signaling. Through our research, we have discovered interesting negative findings in these neurons, which we hope will benefit other laboratories and lead to discussions on their relevance and significance.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Antonio C. Pagano Zottola, Ilenia Severi, Astrid Cannich, Philippe Ciofi, Daniela Cota, Giovanni Marsicano, Antonio Giordano, Luigi Bellocchio
Summary: By activating the CB1 receptor, cannabinoids regulate mitochondrial physiology and energy metabolism in adipocytes through intracellular signaling pathways.
Article
Biochemistry & Molecular Biology
Daniel J. Nasrallah, Neil K. Garg
Summary: This study reports on the synthesis and characterization of two isomeric hexahydrocannabinols (HHCs), (9R)-HHC and (9S)-HHC, which are derivatives of known psychoactive cannabinoids. The researchers used hydrogen-atom transfer reduction to prepare the compounds, with (9R)-HHC being the major diastereomer. They also conducted cannabinoid receptor studies and found that (9R)-HHC has similar binding affinity and activity to Δ9-THC, while (9S)-HHC binds strongly to the receptors but displays reduced activity in functional assays. The variability in HHC isomer ratios found in commercially available products highlights the need for further research and systematic testing of new cannabinoids.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Raj Kamal Srivastava, Inigo Ruiz de Azua, Andrea Conrad, Martin Purrio, Beat Lutz
Summary: This study found that the deletion of CB1 in dbh-positive cells prevents diet-induced obesity through multiple mechanisms including increased sympathetic nervous system activity, reduced NPY activity, and decreased basal hypothalamic-pituitary-adrenal axis activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Xiao Han, Ying Liang, Briana Hempel, Chloe J. Jordan, Hui Shen, Guo-Hua Bi, Jin Li, Zheng-Xiong Xi
Summary: Cannabinoids modulate dopamine transmission and behavior through activation of CB1 receptors. This study found that CB1 receptors are expressed in a subset of dopamine neurons and are involved in cannabinoid modulation of dopamine release and behavior. Deletion of CB1 receptors from dopamine neurons attenuated the effects of cannabinoids on dopamine release, locomotion, and anxiety.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Justin E. LaVigne, Ryan Hecksel, Attila Keresztes, John M. Streicher
Summary: Limited evidence suggests that terpenes found in Cannabis sativa may have cannabimimetic activity and can enhance cannabinoid activity. These multifunctional cannabimimetic ligands provide support for the entourage effect hypothesis, potentially enhancing the therapeutic properties of cannabinoids.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Shuangtao Li, Yuanbing Huang, Lijun Yu, Xiaoyu Ji, Jie Wu
Summary: Cannabinoids, isolated from cannabis and present in animal nervous and immune systems, have shown promising clinical medicinal value, particularly in the field of neurodegenerative diseases such as Alzheimer's disease. This review explores the therapeutic potential of cannabinoids in treating Alzheimer's disease, highlighting their interactions with different endocannabinoid receptor subtypes and the role of the endocannabinoid system in this disease. The underlying mechanisms and potential usefulness of cannabinoids in clinical treatment are also discussed.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Neurosciences
Diego Pascual Cuadrado, Anna Wierczeiko, Charlotte Hewel, Susanne Gerber, Beat Lutz
Summary: This study on genetically engineered mice lacking the cannabinoid type-1 receptor explores gene networks and signaling pathways involved in regulating neural homeostasis. The findings suggest that certain genes and pathways exhibit dichotomic expression, potentially serving as switches to modulate the directionality of neural homeostasis.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2021)
Article
Neurosciences
Tibor M. Brunt, Matthijs G. Bossong
Summary: The endocannabinoid system is a complex neuronal system involved in various biological functions, and its understanding has been driven by the potential therapeutic benefits of cannabinoid ligands. This review provides an overview of the neuropharmacology of cannabinoid receptor ligands, including endocannabinoids, herbal cannabis, and synthetic cannabinoids, focusing on their modulatory actions through other neurotransmitter systems. The effects of cannabinoid ligands on neurotransmitter systems such as dopamine, serotonin, glutamate, noradrenaline, opioid, and GABA are discussed, as well as their therapeutic potential and adverse effects.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Endocrinology & Metabolism
Viktoria B. Horvath, Eszter Soltesz-Katona, Eva Wisniewski, Aniko Rajki, Eszter Halasz, Balazs Enyedi, Laszlo Hunyady, Andras David Toth, Gergo Szanda
Summary: Lowering the expression level of G protein-coupled receptors can reduce proteasomal degradation and offer receptor levels comparable to endogenous CB1 receptors, thus minimizing potential signalling artefacts.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Neurosciences
Urszula Skupio, Julia Welte, Roman Serrat, Abel Eraso-Pichot, Francisca Julio-Kalajzi, Doriane Gisquet, Astrid Cannich, Sebastien Delcasso, Isabelle Matias, Unai B. Fundazuri, Sandrine Pouvreau, Antonio C. Pagano Zottola, Gianluca Lavanco, Filippo Drago, Inigo Ruiz de Azua, Beat Lutz, Luigi Bellocchio, Arnau Busquets-Garcia, Francis Chaouloff, Giovanni Marsicano
Summary: Corticosteroid-mediated stress responses involve complex brain circuits and mitochondrial activity, and the endocannabinoid system plays a role in regulating these processes. The study shows that corticosterone impairs novel object recognition (NOR) task performance in mice through the activation of mitochondrial CB1 receptors and the regulation of neuronal mitochondrial calcium levels. Different brain circuits are modulated by this mechanism to mediate the effects of corticosterone during specific phases of the task.
Review
Biochemistry & Molecular Biology
Maite L. Docampo-Palacios, Giovanni A. Ramirez, Tesfay T. Tesfatsion, Alex Okhovat, Monica Pittiglio, Kyle P. Ray, Westley Cruces
Summary: This article describes the discovery of natural and non-natural hexahydrocannabinols (HHC) by Adam in 1940 and its emergence in the drug market in the United States and some European countries in late 2021. The article provides background information on the synthesis and pharmacology studies of hydrogenated and saturated cannabinoids and discusses the cannabinoid receptor affinities of different types of saturated cannabinoids. The effects of HHC treatment have been studied in vitro and in several animal species in vivo, showing similarities to Δ9-tetrahydrocannabinol (Δ9-THC), but no studies have been conducted in humans to establish its biological profile.
Article
Biochemistry & Molecular Biology
Takafumi Kawai, Hirotaka Narita, Kohtarou Konno, Sharmin Akter, Rizki Tsari Andriani, Hirohide Iwasaki, Shoji Nishikawa, Norihiko Yokoi, Yuko Fukata, Masaki Fukata, Pattama Wiriyasermkul, Pornparn Kongpracha, Shushi Nagamori, Keizo Takao, Tsuyoshi Miyakawa, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Atsushi Nakagawa, Yasushi Okamura
Summary: Voltage-sensing protein TMEM266 has a unique voltage-sensing mechanism and interacts with specific splice variants. The coiled-coil region plays a significant role in forming homodimers, and the cytosolic region at the C-terminal of TMEM266 may bind to various targets. TMEM266 deficiency is associated with behavioral abnormalities.
BIOCHEMICAL JOURNAL
(2022)
Article
Neurosciences
Mayuko Hashimoto, Masaki Fujimoto, Kohtarou Konno, Ming-Liang Lee, Yui Yamada, Koya Yamashita, Chitoku Toda, Michio Tomura, Masahiko Watanabe, Osamu Inanami, Hiroshi Kitamura
Summary: This study reveals that hypothalamic USP2 regulates blood glucose levels through the ROS-AMPK-sympathetic nerve axis. Inhibition of USP2 leads to mitochondrial dysfunction and AMPK phosphorylation, resulting in increased blood glucose and norepinephrine levels.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Eriko Miura, Masahiko Watanabe
Summary: This study investigated the expression of calcineurin (CN) in the mouse brain and found that CNA alpha, CNA, and CNB1 were predominantly expressed. The protein localization experiments revealed that CNB1 and CNA were co-distributed in various cerebellar neurons and glia, while CNA alpha was exclusive to granule cell elements. These findings provide anatomical evidence for the regulatory roles of CN in long-term depression and transmitter release function at synapses.
NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Takeshi Uemura, Emi Suzuki-Kouyama, Shiori Kawase, Taiga Kurihara, Misato Yasumura, Tomoyuki Yoshida, Shuya Fukai, Maya Yamazaki, Peng Fei, Manabu Abe, Masahiko Watanabe, Kenji Sakimura, Masayoshi Mishina, Katsuhiko Tabuchi
Summary: This study found that the presynaptic cell adhesion molecules NRXNs play a crucial role in the survival of cerebellar granule cells and synapse formation. They not only maintain cell survival, but also promote the formation of presynaptic protein clusters and the secretion of neurotrophic factors.
Article
Neurosciences
Keita Mori, Michinori Koebis, Kazuki Nakao, Shizuka Kobayashi, Yuji Kiyama, Masahiko Watanabe, Toshiya Manabe, Yuichi Iino, Atsu Aiba
Summary: This study investigates the function of Calsyntenins (CLSTNs) by generating triple knockout (TKO) mice lacking all CLSTN paralogs. The mutant mice exhibited freezing behavior in novel environments and hypersensitivity to stress. Glucose levels under stress were significantly higher in the mutant mice than in the wild-type controls. Phenotypes such as decreased motivation, which had not been reported in single Clstn knockout mice, were newly discovered. The TKO mice generated in this study serve as an important mouse model for further understanding the function of CLSTN.
Article
Neurosciences
Qin Zhao, Tetsufumi Ito, Chika Soko, Yoshie Hori, Takafumi Furuyama, Hiroyuki Hioki, Kohtarou Konno, Miwako Yamasaki, Masahiko Watanabe, Satoshi Ohtsuka, Munenori Ono, Nobuo Kato, Ryo Yamamoto
Summary: This study investigates the histochemical features of DA(DR-PAG) neurons projecting to the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) in mice. Two subpopulations of these neurons were identified, TH1/VIP- and TH-/VIP1, with the latter being non-DA noncanonical DAT neurons. Both subpopulations innervate the same regions, and the TH-/VIP1 subpopulation was found to be VGlut2-positive neurons.
Article
Neurosciences
Kazue Hisaoka-Nakashima, Kazuto Ohata, Natsuki Yoshimoto, Shintarou Tokuda, Nanako Yoshii, Yoki Nakamura, Dengli Wang, Keyue Liu, Hidenori Wake, Takayuki Yoshida, Yukio Ago, Kouichi Hashimoto, Masahiro Nishibori, Norimitsu Morioka
Summary: Clinical evidence suggests that cognitive impairment is a common comorbidity of chronic pain such as neuropathic pain, but the mechanism behind this impairment remains unclear. This study investigated the role of the proinflammatory molecule HMGB1 and microglial activation in cognitive impairment in mice with neuropathic pain. The findings suggest that blocking HMGB1 or microglial activation could be a novel approach to reducing cognitive impairment associated with neuropathic pain.
EXPERIMENTAL NEUROLOGY
(2022)
Review
Behavioral Sciences
Kana Okada, Kouichi Hashimoto, Kazuto Kobayashi
Summary: Object recognition memory is a fundamental memory mechanism that allows us to identify and recall various features of objects. It has been extensively studied in humans, primates, and rodents to understand the underlying neuropsychological processes involved in mammalian memory and to diagnose neurological diseases such as Alzheimer's and Parkinson's. The central cholinergic system, which is associated with cholinergic cell loss and impairment in recognition memory in the early stages of Alzheimer's, has been investigated to uncover the neural mechanisms underlying recognition memory. Previous studies have suggested that different groups of cholinergic neurons play important roles in different types of object recognition memory, such as memory for object location and object identification. Furthermore, neurodegeneration within the central cholinergic system has been found to cause deficits in object recognition memory in rodent models of Alzheimer's. Understanding how distinct cholinergic cell groups regulate various types of object recognition memory is crucial for elucidating the neuronal mechanisms of recognition memory and developing therapeutic treatments for dementia.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Biology
Amy Cheung, Kotaro Konno, Yuka Imamura, Aya Matsui, Manabu Abe, Kenji Sakimura, Toshikuni Sasaoka, Takeshi Uemura, Masahiko Watanabe, Kensuke Futai, Nils Brose
Summary: The study reveals the involvement of Nrxn genes in the modulation of 5-HT transmission and behavior, suggesting a potential link between Nrxn mutations and ASD.
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
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
Biology
Kieran A. Boyle, Erika Polgar, Maria Gutierrez-Mecinas, Allen C. Dickie, Andrew H. Cooper, Andrew M. Bell, Evelline Jumolea, Adrian Casas-Benito, Masahiko Watanabe, David I. Hughes, Gregory A. Weir, John S. Riddell, Andrew J. Todd
Summary: This study investigates the role of interneurons that continue to express neuropeptide Y (NPY-INs) in the adult mouse spinal cord. The findings suggest that activation of NPY-INs reduces acute pain and pruritogen-evoked itch, while silencing them causes exaggerated itch responses. Silencing another population of inhibitory interneurons also increases itch, but to a lesser extent.
Article
Multidisciplinary Sciences
Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Masahiko Watanabe
Summary: The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to buried target molecules. To solve this problem, we used glyoxal as a fixative, which greatly improved antibody penetration, uncovering signals for buried molecules. Glyoxal also enhanced immunosignals of most other molecules, including the controversial synaptic adhesion molecule Neuroligin 1.
Article
Multidisciplinary Sciences
Reika Kubo, Takayuki Yoshida, Kenji Yamaoka, Kouichi Hashimoto
Summary: In the cerebro-cerebellar loop, the indirect cortico-PG pathway via the mesodiencephalic junction (MDJ) is recruited for perioral sensory transduction. Stimulation of the infraorbital nerve results in enhanced simple spikes (SSs) with short and long latencies, followed by SS inhibition. The second peak signals and SS inhibition are transmitted through the secondary somatosensory area (SII) to the MDJ.
