Article
Neurosciences
Carla L. Busceti, Roxana P. Ginerete, Luisa Di Menna, Giovanna D'Errico, Francesca Cisani, Paola Di Pietro, Tiziana Imbriglio, Valeria Bruno, Giuseppe Battaglia, Francesco Fornai, James A. Monn, Anna Pittaluga, Ferdinando Nicoletti
Summary: Genetic knockout of mGlu2 and mGlu3 receptors affects mice's preference and motor responses to methamphetamine, indicating different roles of these two receptors in methamphetamine addiction. mGlu3(-/-) mice show increased sensitization and elevated levels of phospho-ERK1/2 and free radicals in relevant brain areas, while mGlu2(-/-) mice exhibit reduced motor response to the first methamphetamine injection.
Article
Biochemistry & Molecular Biology
Elissa K. Fultz, Sema G. Quadir, Douglas Martin, Daniel M. Flaherty, Paul F. Worley, Tod E. Kippin, Karen K. Szumlinski
Summary: Methamphetamine (MA) is a highly addictive drug with increasing global use. There is no approved pharmacotherapy for MA use disorder, and little is known about the neurobiological determinants of vulnerability to the disease. Studies suggest that ERK activation in the medial prefrontal cortex may play a role in the affective valence of MA and its reinforcing properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Adam P. Mecca, Kelly Rogers, Zachary Jacobs, Julia W. McDonald, Hannah R. Michalak, Nicole DellaGioia, Wenzhen Zhao, Ansel T. Hillmer, Nabeel Nabulsi, Keunpoong Lim, Jim Ropchan, Yiyun Huang, David Matuskey, Irina Esterlis, Richard E. Carson, Christopher H. van Dyck
Summary: Aging is associated with decreased availability of mGluR5 in the brain, primarily due to tissue loss. This reduction in mGluR5 binding may provide insight into age-related molecular changes and their relationship with brain tissue loss.
Article
Clinical Neurology
J. Titulaer, O. Radhe, K. Danielsson, S. Dutheil, M. M. Marcus, K. Jardemark, T. H. Svensson, G. L. Snyder, M. Ericson, R. E. Davis, A. Konradsson-Geuken
Summary: Lumateperone is a novel drug approved for the treatment of schizophrenia and depressive episodes associated with bipolar depression. It simultaneously modulates key neurotransmitters and improves symptoms while enhancing prosocial behavior. The drug affects dopamine and glutamate signaling, potentially contributing to its effectiveness in improving mood-related symptoms.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Neurosciences
Sergio Garcia Guerra, Andrea Spadoni, Jennifer Mitchell, Irina A. Strigo
Summary: This study investigates the interaction between opioidergic and dopaminergic processing in the human brain during pain-related experiences using radioligand studies. The results show that there is a functional overlap between opioid and dopamine activations in most regions, but also some unique activation areas.
Article
Biochemistry & Molecular Biology
Veronica Rivi, Cristina Benatti, Joan M. C. Blom, Luca Pani, Nicoletta Brunello, Filippo Drago, Francesco Papaleo, Filippo Caraci, Federica Geraci, Sebastiano Alfio Torrisi, Gian Marco Leggio, Fabio Tascedda
Summary: Cognitive impairment in schizophrenia is a challenging problem that hasn't been solved clinically or pharmacologically. Dysfunctional dysbindin and dopamine receptor D3 have been found to improve cognitive functions, but the underlying molecular mechanisms are not fully understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dmitrii S. Traktirov, Ilya R. Nazarov, Valeria S. Artemova, Raul R. Gainetdinov, Nina S. Pestereva, Marina N. Karpenko
Summary: This article explores the roles of dopamine and serotonin in the central nervous system and the impact of knockout of the DAT gene on neurotransmission. The study reveals that excessive dopamine leads to dysregulation of neurotransmission in multiple brain regions and significant effects on the serotonin system. These findings highlight the importance of considering these factors in drug therapies.
Article
Biochemistry & Molecular Biology
Nina Treder, Albert Martinez-Pinteno, Natalia Rodriguez, Nestor Arbelo, Santiago Madero, Marta Gomez, Clemente Garcia-Rizo, Sergi Mas, Patricia Gasso, Eduard Parellada, Constanza Moren
Summary: Schizophrenia is a heterogeneous mental disorder that affects approximately 1% of the global population. One of the main pathophysiological theories suggests an imbalance between excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr). This imbalance may lead to excessive glutamate storms, dendritic pruning, and cellular stress, including nitrosative stress mediated by nitric oxide (NO). The administration of NMDAr antagonists has been found to increase nitric oxide synthase (NOS) levels in specific brain regions, suggesting a potential target for early treatments. In a murine model, the protein levels of NOS were analyzed in the prefrontal cortex (PFC) and ventral hippocampus (HPC) after ketamine-induced schizophrenia, as well as after treatment with clozapine (CLZ) or JNJ-46356479 (JNJ). The findings suggest a dysregulation of the NOS system following NMDAr antagonist administration, which can be modulated by early CLZ and JNJ treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Sergi Ferre, Laura I. Sarasola, Cesar Quiroz, Francisco Ciruela
Summary: Adenosine plays a significant role in modulating striatal neurotransmission, which is mediated by A1 and A2A receptors. The modulation involves different components of the striatal microcircuit and the formation of heteromers. These heteromers have unique properties and provide fine-tune modulation of striatal glutamate release. Targeting these adenosine receptor heteromers may be important for drug development in neuropsychiatric disorders.
Review
Clinical Neurology
Osama Khojah, Seraj Makkawi, Saeed Alghamdi
Summary: This study aimed to systematically review reported cases of anti-mGluR1 encephalitis and summarize their clinical presentation, management, outcomes, and case reports. The study found that anti-mGluR1 encephalitis manifests as symptoms of cerebellar pathology, and early diagnosis with prompt initiation of immunotherapy is crucial for patient recovery.
FRONTIERS IN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christina A. Gates, Donald S. Backos, Philip Reigan, Nicholas R. Natale
Summary: Isoxazolo[3,4-d] pyridazinones ([3,4-d]s) were found to selectively positively modulate metabotropic glutamate receptor (mGluR) Subtypes 2 and 4, with no cross-reactivity at mGluR1a, mGluR5, or mGluR8. Additional analogs were prepared to increase binding affinity, resulting in successful selective lateral metalation and electrophilic quenching at the C3 position.
Review
Cell Biology
Falko Lange, Julia Hoernschemeyer, Timo Kirschstein
Summary: The progression of glioblastomas and tumor-associated epilepsy is closely linked through various pathophysiological mechanisms involving the neurotransmitter glutamate. Current research focuses on the role of glutamate receptors in these diseases and discusses future interventions to interfere with the glutamatergic network.
Article
Cell Biology
M. Crespo, D. A. Leon-Navarro, M. Martin
Summary: Febrile seizures in children can lead to epilepsy in adults, with glutamate playing a key role in the development of neurological disorders. In the short term after seizures, GLT-1 levels increase and glutamate concentration decreases, while mGlu(5)R levels remain unchanged. However, in the long term, an increase in mGlu(5)R levels and decreases in GLT-1 and glutamate levels are observed, associated with the development of an anxious phenotype and potentially increased vulnerability to epileptic events in adults.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Deepa Gautam, Ulhas P. Naik, Meghna U. Naik, Santosh K. Yadav, Rameshwar Nath Chaurasia, Debabrata Dash
Summary: This paper explores the role of platelets in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as the critical role of glutamate receptors in the pathophysiology of these diseases. By reviewing data from clinical trials, animal models, and cellular studies, it reveals the involvement of glutamate receptor dysfunction in neurodegenerative processes and provides an overview of current treatments, including glutamate receptor antagonists, for AD and PD.
Article
Neurosciences
Kevin W. McCairn, Yuji Nagai, Yukiko Hori, Taihei Ninomiya, Erika Kikuchi, Ju-Young Lee, Tetsuya Suhara, Atsushi Iriki, Takafumi Minamimoto, Masahiko Takada, Masaki Isoda, Masayuki Matsumoto
Article
Radiology, Nuclear Medicine & Medical Imaging
Kazumi Koga, Yuji Nagai, Masayuki Hanyu, Mitsukane Yoshinaga, Shigeyuki Chaki, Norikazu Ohtake, Satoshi Ozaki, Ming-Rong Zhang, Tetsuya Suhara, Makoto Higuchi
JOURNAL OF NUCLEAR MEDICINE
(2017)
Article
Chemistry, Medicinal
Ran Cheng, Wakana Mori, Longle Ma, Mireille Alhouayek, Akiko Hatori, Yiding Zhang, Daisuke Ogasawara, Gengyang Yuan, Zhen Chen, Xiaofei Zhang, Hang Shi, Tomoteru Yamasaki, Lin Xie, Katsushi Kumata, Masayuki Fujinaga, Yuji Nagai, Takafumi Minamimoto, Mona Svensson, Lu Wang, Yunfei Du, Mary Jo Ondrechen, Neil Vasdev, Benjamin F. Cravatt, Christopher Fowler, Ming-Rong Zhang, Steven H. Liang
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Clinical Neurology
Ken-ichi Inoue, Shigehiro Miyachi, Katsunori Nishi, Haruo Okado, Yuji Nagai, Takafumi Minamimoto, Atsushi Nambu, Masahiko Takada
MOVEMENT DISORDERS
(2019)
Article
Neurosciences
Atsushi Fujimoto, Yukiko Hori, Yuji Nagai, Erika Kikuchi, Kei Oyama, Tetsuya Suhara, Takafumi Minamimoto
JOURNAL OF NEUROSCIENCE
(2019)
Article
Chemistry, Medicinal
Yasushi Hattori, Kazunobu Aoyama, Jun Maeda, Naoto Arimura, Yasuko Takahashi, Masako Sasaki, Masayuki Fujinaga, Chie Seki, Yuji Nagai, Kazunori Kawamura, Tomoteru Yamasaki, Ming-Rong Zhang, Makoto Higuchi, Tatsuki Koike
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Tomoyuki Miyazaki, Waki Nakajima, Mai Hatano, Yusuke Shibata, Yoko Kuroki, Tetsu Arisawa, Asami Serizawa, Akane Sano, Sayaka Kogami, Tomomi Yamanoue, Kimito Kimura, Yushi Hirata, Yuuki Takada, Yoshinobu Ishiwata, Masaki Sonoda, Masaki Tokunaga, Chie Seki, Yuji Nagai, Takafumi Minamimoto, Kazunori Kawamura, Ming-Rong Zhang, Naoki Ikegaya, Masaki Iwasaki, Naoto Kunii, Yuichi Kimura, Fumio Yamashita, Masataka Taguri, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Michisuke Yuzaki, Hiroki Kato, Makoto Higuchi, Hiroyuki Uchida, Takuya Takahashi
Article
Cell Biology
Taketsugu Hayashi, Ryota Akikawa, Keisuke Kawasaki, Jun Egawa, Takafumi Minamimoto, Kazuto Kobayashi, Shigeki Kato, Yukiko Hori, Yuji Nagai, Atsuhiko Iijima, Toshiyuki Someya, Isao Hasegawa
Article
Neurosciences
Yuji Nagai, Naohisa Miyakawa, Hiroyuki Takuwa, Yukiko Hori, Kei Oyama, Bin Ji, Manami Takahashi, Xi-Ping Huang, Samuel T. Slocum, Jeffrey F. DiBerto, Yan Xiong, Takuya Urushihata, Toshiyuki Hirabayashi, Atsushi Fujimoto, Koki Mimura, Justin G. English, Jing Liu, Ken-ichi Inoue, Katsushi Kumata, Chie Seki, Maiko Ono, Masafumi Shimojo, Ming-Rong Zhang, Yutaka Tomita, Jin Nakahara, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Jian Jin, Bryan L. Roth, Takafumi Minamimoto
NATURE NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Yukiko Hori, Yuji Nagai, Koki Mimura, Tetsuya Suhara, Makoto Higuchi, Sebastien Bouret, Takafumi Minamimoto
Summary: In this study, the specific contributions of D1R and D2R dopamine receptors to cost-benefit trade-off in motivation were investigated using pharmacological manipulation and PET imaging in macaque monkeys. The findings showed that blocking either D1R or D2R affected reward processing and delay discounting, with D2R antagonism selectively increasing workload discounting. Blocking both receptors had synergistic effects on delay discounting but had an antagonist effect on workload discounting, providing insights into the regulation of motivational alterations in neurological and psychiatric disorders.
Article
Biology
Yukiko Hori, Koki Mimura, Yuji Nagai, Atsushi Fujimoto, Kei Oyama, Erika Kikuchi, Ken-ichi Inoue, Masahiko Takada, Tetsuya Suhara, Barry J. Richmond, Takafumi Minamimoto
Summary: The study reveals that neuronal activity in the dorsal part of the primate caudate head (dCDh) signals the temporally discounted value needed to calculate motivation for delayed rewards, and inactivation of dCDh distorts task performance based on reward size and delay integration, but not for different reward sizes without delay.
Article
Multidisciplinary Sciences
Kei Oyama, Yukiko Hori, Yuji Nagai, Naohisa Miyakawa, Koki Mimura, Toshiyuki Hirabayashi, Ken-ichi Inoue, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Takafumi Minamimoto
Summary: The researchers found distinct roles of prefronto-subcortical pathways in working memory and decision-making by using chemogenetic intervention, providing a new technical approach for dissecting cognitive neural circuits in primates.
Article
Neurosciences
Kei Oyama, Yukiko Hori, Yuji Nagai, Naohisa Miyakawa, Koki Mimura, Toshiyuki Hirabayashi, Ken-Ichi Inoue, Masahiko Takada, Makoto Higuchi, Takafumi Minamimoto
Summary: The chemogenetic technology known as DREADDs provides a reversible method for controlling neuronal activity and investigating its correlation with behavior. This study examines the pharmacokinetics and behavioral effects of the DREADD actuator Deschloroclozapine (DCZ) in macaque monkeys. The results show that orally administered DCZ can effectively manipulate neuronal activity in a chronic and reversible manner, with potential for clinical application.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Kei Oyama, Yukiko Hori, Koki Mimura, Yuji Nagai, Mark A. G. Eldridge, Richard C. Saunders, Naohisa Miyakawa, Toshiyuki Hirabayashi, Yuki Hori, Ken-ichi Inoue, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Barry J. Richmond, Takafumi Minamimoto
Summary: This study used DREADDs technology to disrupt the interaction between OFC and rmCD in monkeys, and found that it significantly affected the sensitivity to cued reward value for goal-directed behavior. This finding extends the understanding of the physiological basis of psychiatric disorders.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Naohisa Miyakawa, Yuji Nagai, Yukiko Hori, Koki Mimura, Asumi Orihara, Kei Oyama, Takeshi Matsuo, Ken-ichi Inoue, Takafumi Suzuki, Toshiyuki Hirabayashi, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Keisuke Kawasaki, Takafumi Minamimoto
Summary: Pharmacological and surgical treatments of epilepsy have limited success, therefore a more targeted and on-demand approach is desired. The authors demonstrate the use of inhibitory chemogenetics to attenuate cortical seizures and subsequent convulsions in nonhuman primates. These results highlight the efficacy of DREADDs for treating epilepsy in a primate model.
NATURE COMMUNICATIONS
(2023)