Article
Neurosciences
Mikyung Kim, Raly James Custodio, Hyun Jun Lee, Leandro Val Sayson, Darlene Mae Ortiz, Bung-Nyun Kim, Hee Jin Kim, Jae Hoon Cheong
Summary: Several individuals worldwide show cognitive impairment due to various reasons. This study aimed to investigate the pathways potentially involved in cognitive impairment using Per2 transgenic animals. The findings suggest that Per2 expression levels might influence spatial working memory performance via DRD1-PKA-CREB-dependent signaling.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Behavioral Sciences
Youjun Yang, Zhanqiong Zhong, Baojia Wang, Yili Wang, Weijun Ding
Summary: Lack of maternal care and attention during infancy and childhood can lead to neuropsychiatric disorders in adulthood, but the underlying neuroregulatory signaling has not been extensively studied. This study shows that unpredictable maternal separation in mice impairs neuronal development in the medial prefrontal cortex and causes long-lasting behavioral changes. The downregulation of dopamine D1 receptor in the mPFC appears to play a role in these abnormalities. Activating D1R signaling in the mPFC improves neuronal excitability and rescues the behavioral and cognitive dysfunction caused by maternal deprivation.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Multidisciplinary Sciences
Youtong Huang, Greg Lemke
Summary: Recurrent seizures, which may contribute to the pathogenesis and cognitive decline of Alzheimer's disease, are common in early-stage AD and mouse models that overproduce amyloid beta. In a study of the APP/PS1 mouse model, it was found that the mutation of TAM receptor tyrosine kinase (RTK) Mer or its ligand Gas6 significantly increased the risk of early death, which was tied to violent seizures originating in the dentate gyrus of the hippocampus. TAM-deficient mice showed increased newborn DG neurons and excitatory synapses, coinciding with premature death and adult neurogenesis. In contrast, the incidence of lethal seizures was strongly anticorrelated with the deposition of dense-core amyloid plaques. These findings suggest that TAM-mediated phagocytosis influences synaptic connectivity in the hippocampus and that seizure-inducing amyloid beta polymers are present before the formation of dense-core plaques.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Yafang Zhang, Jennifer Ben Nathan, Amanda Moreno, Riley Merkel, Michelle W. Kahng, Matthew R. Hayes, Benjamin C. Reiner, Richard C. Crist, Heath D. Schmidt
Summary: The high rates of relapse associated with current medications used to treat opioid use disorder (OUD) necessitate research that expands our understanding of the neural mechanisms regulating opioid taking to identify molecular substrates that could be targeted by novel pharmacotherapies to treat OUD. Recent studies show that activation of calcitonin receptors (CTRs) is sufficient to reduce the rewarding effects of addictive drugs in rodents. Central CTR signaling was investigated in the context of opioid-mediated behaviors using single nuclei RNA sequencing (snRNA-seq), fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) techniques. CTR expression was found in specific cell types in the nucleus accumbens (NAc), with interesting disparities between D1R- and D2R-expressing medium spiny neurons (MSNs). Functional significance was revealed through knockdown experiments, with reduced CTR expression in D1R- versus D2R-expressing MSNs potentiating/augmenting opioid self-administration and attenuating it, respectively.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Christian Baeuchl, Franka Gloeckner, Christoph Koch, Johannes Petzold, Nicolas W. Schuck, Michael N. Smolka, Shu-Chen Li
Summary: The aging process leads to changes in spatial navigation behavior, with older adults relying more on proximal location cues instead of environmental boundaries. Deficient dopaminergic modulation may contribute to errors during spatial navigation in older adults. Administering levodopa in young and older adults affected brain responses and memory retrieval differently, with older adults showing upregulation in the medial temporal lobe and brainstem. While L-DOPA had no effect on older adults' overall memory performance, it improved spatial memory and increased boundary processing in some individuals.
Article
Cell Biology
Hui-Chiun Tseng, Chien-Yuan Pan
Summary: Neuroinflammation is an early event in the pathogenesis of neurodegenerative disorders. This study shows that dopamine-induced elevation of intracellular Zn2+ concentration via the D1-like receptor (D1R) initiates a transient inflammatory response leading to cell death. Maintaining a balance between dopamine homeostasis and inflammatory responses is an important therapeutic target for neurodegeneration.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Review
Behavioral Sciences
Mayuri Shukla, Bruno Vincent
Summary: Methamphetamine abuse can have detrimental effects on various parts of the memory system, including the learning process. The structural similarities between this drug and dopamine can lead to cognitive deficits and potentially trigger neurodegenerative disorders.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Behavioral Sciences
Ana Luiza Alves Dias, Adriana Maria Fernandes de Oliveira Golzio, Bruno Henrique de Lima Santos, Mirian Graciela da Silva Stiebbe Salvadori, Socrates Golzio dos Santos, Marcelo Sobral da Silva, Reinaldo Nobrega de Almeida, Flavio Freitas Barbosa
Summary: Studies have shown that caffeine can improve the consolidation of episodic-like memory in Wistar rats, leading to increased dopamine turnover rate in the hippocampus.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Environmental Sciences
Bo Zhang, Hang Li, Yan Wang, Yang Li, Zhongsheng Zhou, Xuejia Hou, Xiaowen Zhang, Te Liu
Summary: This study aimed to elucidate the molecular mechanisms of cognitive impairment in rats following chronic lead exposure and mitigate or prevent lead toxicity in the central nervous system. Lead exposure caused significant damage to rat nervous systems, including increased autophagosomes in hippocampal neurons, decreased IGF-1 levels, decreased gene expression of IGF-1, IGF-1R, PI3K, Akt, and mTOR, and upregulated levels of autophagy-associated proteins. In vivo intervention experiments using an autophagy inhibitor showed that it inhibited lead-induced autophagy and autophagy-related gene expression, possibly through activation of the IGF-1 pathway. Overall, lead may activate hippocampal autophagy through the IGF-1/PI3K/Akt/mTOR signaling pathway.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Hari K. Namballa, Ann M. Decker, Michael Dorogan, Ashok Gudipally, Jakub Goclon, Wayne W. Harding
Summary: The tolerance of fluoroalkoxylated groups on the C-3 and C-9 positions of tetrahydroprotoberberines (THPBs) towards D1R activity was investigated. It was found that a 1,1-difluoroethoxy substituent on the C-3 position showed D1R antagonist activity. Compound 13a demonstrated the highest potency as a cAMP-based D1R antagonist, with selectivity for D1R and no affinity for D2R. Further studies are needed to explore the pharmacological properties of (S)-stepholidine congeners and their potential as novel D1R-targeted agents.
BIOORGANIC CHEMISTRY
(2023)
Article
Integrative & Complementary Medicine
Chih-Sheng Chen, Chi-Fong Lin, Yung-Lan Chou, Der-Yen Lee, Peng-Tai Tien, Yao-Chien Wang, Ching-Yao Chang, En-Shyh Lin, Jamie Jiin Chen, Ming-Yen Wu, Hsiangyu Ku, Dekang Gan, Yung-Ming Chang, Hui-Ju Lin, Lei Wan
Summary: The aim of this study was to investigate whether acupuncture suppresses myopia progression in form deprived Syrian hamsters by increasing dopamine levels and inhibiting inflammasome activation. The results showed that acupuncture inhibited myopia development by increasing dopamine levels and activating the dopamine D1 receptor signaling pathway. Additionally, the study demonstrated that activation of the D1 receptor signaling pathway suppressed the activation of the NOD-LRR-NLRP3 inflammasome. Therefore, our findings suggest that acupuncture inhibits myopia development by suppressing inflammation initiated by the dopamine-D1 receptor signaling pathway.
ACUPUNCTURE IN MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Ali A. Shati, Attalla F. El-Kott, Mahmoud A. Alkhateeb
Summary: The study evaluated the protective effect of RVD1 against cadmium chloride-induced hippocampal damage and memory loss in rats by modulating the PTEN/PI3K/Akt/mTOR pathway. RVD1 improved memory function, preserved hippocampal structure, and suppressed ROS generation, TNF-alpha, IL-6, NF-kappa B, while stimulating levels of GSH, MnSOD, and Bcl2 in CdCl2-treated rats.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2022)
Review
Clinical Neurology
Sanya Rastogi, Kimford J. Meador, William B. Barr, Orrin Devinsky, Beth A. Leeman-Markowski
Summary: Studies of epilepsy patients provide insights into the neuroscience of human memory. The impairment of remote memory in patients may result from the interaction of multiple factors, including hippocampal dysfunction. The lateralization of remote memory has been the focus of research, with left temporal lobe epilepsy patients experiencing more severe deficits than others.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Peng Wang, Lu Yang, Rang Yang, Zhangping Chen, Xiaofan Ren, Fangjiao Wang, Yan Jiao, Yuxin Ding, Fengyuan Yang, Tao Sun, Huisheng Ma
Summary: This study investigated the early phases of seizure events in the hippocampus of lithium-pilocarpine induced epileptic rats. The differential expression of proteins in the hippocampus on day 1 and day 3 was analyzed, revealing that the differentially expressed proteins likely play a role in enhancing seizure activity. The regulated proteins differed between day 1 and day 3, indicating the involvement of different molecules and pathways in seizure events.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Plant Sciences
Meizhu Zheng, Minghui Chen, Chunming Liu, Yajun Fan, Dongfang Shi
Summary: This study found that URA can effectively protect neurons in mouse models of PD by up-regulating the PI3K/Akt/mTOR signaling pathway, improving behavioral performance, and preventing dopamine metabolism.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Emma Puighermanal, Laia Castell, Anna Esteve-Codina, Su Melser, Konstantin Kaganovsky, Charleine Zussy, Jihane Boubaker-Vitre, Marta Gut, Stephanie Rialle, Christoph Kellendonk, Elisenda Sanz, Albert Quintana, Giovanni Marsicano, Miquel Martin, Marcelo Rubinstein, Jean-Antoine Girault, Jun B. Ding, Emmanuel Valjent
NATURE COMMUNICATIONS
(2020)
Article
Neurosciences
Daniel Rial, Emma Puighermanal, Marine Chazalon, Emmanuel Valjent, Serge N. Schiffmann, Alban de Kerchove d'Exaerde
BIOLOGICAL PSYCHIATRY
(2020)
Article
Biochemistry & Molecular Biology
Laura Cutando, Emma Puighermanal, Laia Castell, Pauline Tarot, Federica Bertaso, Patricia Bonnavion, Alban de Kerchove d'Exaerde, Elsa Isingrini, Micaela Galante, Glenn Dallerac, Vincent Pascoli, Christian Luescher, Bruno Giros, Emmanuel Valjent
Summary: The study found that d-amphetamine and methylphenidate can increase phosphorylation of GluA1 in the membrane fraction of the mouse cerebellum; Bergmann glial cells are the source of pS845-GluA1 and intact NE release is required; NE regulates GluA1 phosphorylation in Bergmann glial cells in response to prescription stimulants.
Review
Neurosciences
Emmanuel Valjent, Giuseppe Gangarossa
Summary: The dorsal striatum plays a critical role in controlling motor behaviors and recent studies have shown that the tail of striatum (TS) represents an additional functional domain with unique input-output connectivity, making it an integrator of sensory processing.
TRENDS IN NEUROSCIENCES
(2021)
Article
Environmental Sciences
Isabel Forner-Piquer, Wendy Klement, Giuseppe Gangarossa, Emma Zub, Frederic de Bock, Marine Blaquiere, Tangui Maurice, Etienne Audinat, Adele Faucherre, Frederic Lasserre, Sandrine Ellero-Simatos, Laurence Gamet-Payrastre, Chris Jopling, Nicola Marchi
Summary: The study found that male offspring of mice exposed to a pesticide cocktail exhibited anxiety-like behavior, while zebrafish larvae exposed to the pesticide cocktail during development showed alterations in motor behaviors.
ENVIRONMENTAL POLLUTION
(2021)
Review
Endocrinology & Metabolism
Chloe Berland, Dana M. Small, Serge Luquet, Giuseppe Gangarossa
Summary: The abundance of energy-dense and palatable diets in the modern food environment contributes to the obesity pandemic; recent reports suggest that dietary lipids can modulate dopamine transmission, potentially leading to maladaptations of the dopamine system.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2021)
Review
Pharmacology & Pharmacy
Mathieu Favier, Nicolas Pietrancosta, Salah El Mestikawy, Giuseppe Gangarossa
Summary: VGLUT3, an atypical vesicular transporter, is expressed in various types of neurons and plays a critical role in modulating brain functions through glutamate co-transmission. Targeting VGLUT3 for therapeutic strategies could lead to breakthroughs in treating conditions such as Parkinson's disease and addiction.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chloe Berland, Julien Castel, Romano Terrasi, Enrica Montalban, Ewout Foppen, Claire Martin, Giulio G. Muccioli, Serge Luquet, Giuseppe Gangarossa
Summary: This study explores the functional connection between the gut-brain axis and the reward and homeostatic brain structures using a physiologically relevant binge eating (BE) mouse model and multiscale in vivo approaches. The results reveal that compensatory adaptations in response to BE require the gut-to-brain axis, which relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling through the vagus nerve. Inhibition of peripheral CB1 receptors increases hypothalamic activity, modulates metabolic efficiency, and dampens mesolimbic dopamine circuit activity, suppressing palatable eating. This study provides compelling evidence for a yet unappreciated physiological integrative mechanism involving peripheral eCBs and the vagus nerve in regulating homeostatic and reward-driven feeding.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Enrica Montalban, Albert Giralt, Lieng Taing, Evelien H. S. Schut, Laura F. Supiot, Laia Castell, Yuki Nakamura, Benoit de Pins, Assunta Pelosi, Laurence Goutebroze, Pola Tuduri, Wei Wang, Katrina Daila Neiburga, Letizia Vestito, Julien Castel, Serge Luquet, Angus C. Nairn, Denis Herve, Nathaniel Heintz, Claire Martin, Paul Greengard, Emmanuel Valjent, Frank J. Meye, Nicolas Gambardella, Jean-Pierre Roussarie, Jean-Antoine Girault
Summary: Forebrain dopamine-sensitive neurons play important roles in movement, action selection, motivation, and working memory. This study compares different populations of dopaminoceptive neurons and identifies differences in gene expression between them. Additionally, it reveals the potential role of prostaglandin E2 as a neuromodulator in the striatum and a potential therapeutic target.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Clarisse Dumont, Guangping Li, Julien Castel, Serge Luquet, Giuseppe Gangarossa
Summary: The regulation of food intake and energy balance relies on the integration of signals monitoring nutritional, metabolic, cognitive, and emotional states. The paraventricular thalamus (PVT) is a central hub that may contribute to the regulation of feeding and homeostatic/allostatic processes. This study reveals the role of catecholaminergic (CA) inputs from the hindbrain to the PVT in scaling feeding and metabolic efficiency, as well as the modulation of downstream hypothalamic neuron activity.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
Blazej D. Pedzich, Sarah Rubens, Mehdi Sekssaoui, Anouk Pierre, Andries Van Schuerbeek, Philippe Marin, Joel Bockaert, Emmanuel Valjent, Carine Becamel, Dimitri De Bundel
Summary: Psychedelic-assisted psychotherapy has gained attention as a novel treatment strategy for fear-related mental disorders. This study investigated the effect of activating the serotonin 2A (5-HT2A) receptor, a key target for psychedelics, on emotional processing. The findings suggest that activation of 5-HT2A receptors in the amygdala suppresses fear expression and reduces anxiety-like behavior, providing insights into the underlying mechanisms of psychedelic-assisted therapy.
NEUROPSYCHOPHARMACOLOGY
(2022)
Editorial Material
Neurosciences
F. Javier Rubio, Emmanuel Valjent, Bruce T. Hope
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Oriane Onimus, Emmanuel Valjent, Gilberto Fisone, Giuseppe Gangarossa
Summary: This study focuses on the regulatory mechanisms of antipsychotic drugs on immediate early genes in the striatum. The results show that the induction of immediate early genes in the striatum requires the synergistic activation of A2a and NMDA receptors, while the PKA/DARPP-32 and mTOR pathways also cooperate in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Roberta Haddad-Tovolli, Sara Ramirez, Emma Munoz-Moreno, Maria Mila-Guasch, Lluis Miquel-Rio, Macarena Pozo, Inigo Chivite, Jordi Altirriba, Arnaud Obri, Alicia G. Gomez-Valades, Miriam Toledo, Elena Eyre, Analia Bortolozzi, Emmanuel Valjent, Guadalupe Soria, Marc Claret
Summary: Preparation for motherhood involves various physiological and behavioral adjustments to create an optimal environment for embryonic development. Pregnant women often experience cravings for highly palatable foods, which can contribute to overweight or obesity. The neurobiology behind specific food cravings during pregnancy is still unknown. This study shows that mice, like humans, have pregnancy food craving-like episodes, which are associated with changes in brain connectivity. Dopaminergic signaling in the nucleus accumbens, regulated by dopamine D2 receptors, plays a role in modulating these food craving-like events. Importantly, persistent maternal food craving-like behavior can have long-lasting effects on offspring, particularly in males, leading to metabolic and neuropsychological health issues in adulthood.