Article
Biochemistry & Molecular Biology
Benjamin Davidson, Peter Giacobbe, Tony P. George, Sean M. Nestor, Jennifer S. Rabin, Maged Goubran, Alexander J. Nyman, Anusha Baskaran, Ying Meng, Christopher B. Pople, Simon J. Graham, Fred Tam, Clement Hamani, Nir Lipsman
Summary: Alcohol use disorder (AUD) is a common and difficult-to-treat illness. Deep brain stimulation (DBS) in the nucleus accumbens (NAc) has shown potential in reducing alcohol-related symptoms. Clinical and imaging studies have found that NAc-DBS can lead to decreased metabolism in the NAc, reduced functional connectivity to other brain regions, and decreased activation in neural circuits related to alcohol cue-reactivity, resulting in improvements in AUD.
MOLECULAR PSYCHIATRY
(2022)
Review
Chemistry, Medicinal
Hajime Miyanishi, Atsumi Nitta
Summary: Depression is a common mental illness with increasing global prevalence, and about 30% of patients are resistant to treatment. The brain-derived neurotrophic factor (BDNF) plays a crucial role in depression pathogenesis, but its regulation needs to be targeted. Recent research has revealed a novel function of BDNF in the dorsal striatum, which may contribute to vulnerability to social stress.
Article
Neurosciences
Andrea Miuli, Giacomo d'Andrea, Mauro Pettorruso, Gianluca Mancusi, Alessio Mosca, Francesco Di Carlo, Giovanni Martinotti, Massimo di Giannantonio
Summary: This article discusses the potential role of Brain-Derived Neurotrophic Factor (BDNF) as a biomarker for the different stages of Cocaine Use Disorder (CUD) and its close relationship with the clinical course of CUD. The authors suggest that finding valuable biomarkers for CUD severity and disease stage could greatly benefit CUD patients.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Psychiatry
Bangkun Yang, Lesheng Wang, Ying Nie, Wei Wei, Wenping Xiong
Summary: The study revealed that proBDNF plays a significant role in the pathophysiology of PSD, affecting cellular apoptosis and depression-related proteins. The mechanism may involve the promotion of cellular apoptosis and the inhibition of nerve synapse regeneration by proBDNF, contributing to the progression of PSD.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Psychiatry
Lea Tochon, Rose-Marie Vouimba, Marc Corio, Nadia Henkous, Daniel Beracochea, Jean-Louis Guillou, Vincent David
Summary: This study found that chronic alcohol consumption and alcohol withdrawal modulate the use of spatial and single cue-based learning strategies, and enhance the association between addictive substances and the reward system through the activation of the amygdala. This cognitive imbalance could contribute to maintain addictive behaviors and increase the risk of relapse.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Neurosciences
Yann Ehinger, Drishti Soneja, Khanhky Phamluong, Alexandra Salvi, Dorit Ron
Summary: This study characterized the distribution of brain-derived neurotrophic factor (BDNF) in the corticostriatal circuitry using transgenic mice and viral tracing techniques. It was found that BDNF is expressed in all subregions of the prefrontal cortex (PFC) and the connectivity of BDNF neurons with the striatum varies across different cortical regions.
Article
Endocrinology & Metabolism
Tim Gruber, Cristina Garcia-Caceres
Summary: This study reveals that the BDNF-TrkB signalling pathway is not only regulated by neurons, but also by astrocytic TrkB.T1. Defective signalling of TrkB.T1 in hypothalamic circuits leads to obesity.
Article
Behavioral Sciences
Chuya Jing, Changxin Jing, Liangcheng Zheng, Ganji Hong, Jingjing Zheng, Lu Yu, Ningning Song, Tengkun Zhang, Qilin Ma, Jie Fang
Summary: By studying 11 smoking addicts with dorsal striatum damage and 20 controls, it was found that disruption of smoking addiction was significantly associated with the dorsal striatum. Patients with dorsal striatum damage were more likely to successfully quit smoking and reduce the urge to smoke.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Lei An, Mengxue Li, Cunen Zou, Ke Wang, Wei Zhang, Xiaolong Huang, Yousheng Wang
Summary: Accumulating evidence suggests that walnut polyphenols (WP) and their metabolites urolithins have protective effects on oxidative stress-induced damage in human neuroblastoma cells. The activation of cAMP-response element binding protein (CREB)-mediated signaling pathway, as well as the up-regulation of brain-derived neurotrophic factor (BDNF), is involved in the neuroprotective effects of WP and urolithin A (UroA). This study provides new insights into the beneficial effects of WP and UroA on brain function.
Article
Biochemistry & Molecular Biology
Rong-Wei Kou, Bing Xia, Rui Han, Zhi-Qing Li, Jun-Ren Yang, Xia Yin, Yu-Qi Gao, Jin-Ming Gao
Summary: This study identified 10 secondary metabolites, including a new lanostane triterpenoid named 2 alpha-hydroxy-inotodiol (2 alpha-HI), from the edible mushroom I. obliquus. The results showed that 2 alpha-HI exhibited remarkable neuroprotective activity against oxidative stress and apoptosis induced by H2O2 in SH-SY5Y cells, mediated by the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Additionally, the neuroprotective effects of 2 alpha-HI were preliminarily verified in zebrafish.
Article
Immunology
Samuel Fleury, Imane Boukhatem, Jessica Le Blanc, Melanie Welman, Marie Lordkipanidze
Summary: Platelets and neurons share many similarities in terms of secretory mechanisms and neurotransmitter regulation, with platelets serving as a potential peripheral biomarker for neuronal pathologies due to their high levels of brain-derived neurotrophic factor (BDNF). Despite the abundance of BDNF in platelets, discrepancies in the detection of BDNF receptors on platelets, such as TrkB and p75(NTR), suggest caution in using antibody-based assays for studying neurological disorders. Rigorous characterization of antibodies and bioassays is crucial to understanding the relationship between platelet and neuronal biology of BDNF.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michael Freissmuth
Summary: The level of dopamine transporters in the neuronal plasma membrane affects learning and motor coordination in mice. Kearney and colleagues recently showed that dopamine autoreceptors and metabotropic glutamate receptors control the cycling of dopamine transporters in the presynaptic specialization of dopaminergic neurons. These findings have important implications for future studies in neural development and motor learning.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Katherine Aby, Ryan Antony, Mary Eichholz, Rekha Srinivasan, Yifan Li
Summary: The study revealed that upregulation of pro-BDNF and activation of p75NTR pathway are involved in denervation-induced inflammation in skeletal muscle. Inhibition of p75NTR and knockout of BDNF can reduce inflammation in denervated muscle, suggesting a new target for treating skeletal muscle inflammation.
Article
Biochemistry & Molecular Biology
Min Liu, Shouhong Mu, Weikai Han, Xu Tan, E. Liu, Zhaofang Hang, Shaowei Zhu, Qingwei Yue, Jinhao Sun
Summary: The study demonstrated that methamphetamine (MA) increases c-Fos expression and synaptic plasticity in the orbitofrontal cortex (OFC) and dorsal striatum (DS). MA activates projection neurons from the OFC to the DS and affects conditioned place preference (CPP) scores. The study also showed that DA release in the OFC is increased in the MA group, and D1R neurons in the OFC-DS pathway play a role in MA addiction.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biology
Yu-Young Tsai, Chiu-Lun Shen, D. Dhananjaya, Ching-Yen Tsai, Woan-Yuh Tarn
Summary: Knockout of the RBM4 gene leads to foliation defects in the cerebellum and delayed motor learning in mice, which are similar to neurotrophin deficiency. RBM4 promotes the expression of BDNF and enhances BDNF-TrkB signaling. Prenatal supplementation with a TrkB agonist rescues cerebellar malformation and improves motor learning in RBM4 knockout mice.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Aliza T. Ehrlich, Meriem Semache, Pierre Couvineau, Stefan Wojcik, Hiroyuki Kobayashi, Marcus Thelen, Florence Gross, Mireille Hogue, Christian Le Gouill, Emmanuel Darcq, Michel Bouvier, Brigitte L. Kieffer
Summary: Researchers have generated Ackr3-Venus knock-in mice to track the ACKR3 receptor, enabling direct detection of the receptor under physiological conditions and revealing its expression patterns in the brain.
Article
Biochemistry & Molecular Biology
Virgile Clergue-Duval, Agathe Vrillon, Jerome Jeanblanc, Frank Questel, Julien Azuar, Gregory Fouquet, Francois Mouton-Liger, Dorian Rollet, Eric Hispard, Elodie Bouaziz-Amar, Vanessa Bloch, Alexandra Dereux, Emmanuel Cognat, Cynthia Marie-Claire, Jean-Louis Laplanche, Frank Bellivier, Claire Paquet, Mickael Naassila, Florence Vorspan
Summary: This translational study investigated the potential of plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as predictive biomarkers of alcohol withdrawal-associated brain toxicity. The study found that NfL levels were higher in the alcohol cessation group and tau and UCHL1 levels were positively associated with diazepam dosage. In a preclinical study, NfL levels were higher in the alcohol deprivation effect (ADE) model. Plasma tau, NfL and UCHL1 show promise as biomarkers of brain suffering during alcohol withdrawal.
Article
Biochemistry & Molecular Biology
Sami Ben Hamida, Michelle Carter, Emmanuel Darcq, Marion Sourty, Md Toufiqur Rahman, Ann M. Decker, Chunyang Jin, Brigitte L. Kieffer
Summary: The study demonstrates that RTI-13951-33 can reduce alcohol drinking behavior in mice while leaving water drinking behavior intact. The compound is effective in C57BL/6 mice but not Gpr88 knockout mice, indicating its specificity in vivo. Additionally, RTI-13951-33 decreases alcohol self-administration and reduces the expression of alcohol reward-seeking behavior, suggesting its potential therapeutic effect for alcohol use disorders.
Article
Neurosciences
Julie Bailly, Florence Allain, Eric Schwartz, Chloe Tirel, Charles Dupuy, Florence Petit, Marco A. Diana, Emmanuel Darcq, Brigitte L. Kieffer
Summary: This study found that the mu opioid receptor in the brain can promote aversive emotional states, and it is controlled by two different neural pathways (Hb-MOR/interpeduncular nucleus and Hb-MOR/dorsal raphe nucleus) that regulate despair and anxiety, respectively. These findings are important for understanding emotional balance and addiction mechanisms.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Endocrinology & Metabolism
Luca Posa, Danilo De Gregorio, Martha Lopez-Canul, Qianzi He, Emmanuel Darcq, Laura Rullo, Leora Pearl-Dowler, Livio Luongo, Sanzio Candeletti, Patrizia Romualdi, Brigitte Lina Kieffer, Gabriella Gobbi
Summary: In this study, the relationship between melatonin MT2 receptors and the opioid system in neuropathic pain was investigated. The results showed that the antiallodynic effects of a melatonin MT2 agonist required the activation of mu opioid receptors (MORs), but not delta opioid receptors (DORs). Electrophysiological recordings and immunohistochemistry studies revealed that the interaction between MORs and MT2 receptors within a neuronal circuit in the brain was responsible for the analgesic effects of the MT2 agonist.
JOURNAL OF PINEAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sami Ben Hamida, Sarojini M. Sengupta, Ellie Clarke, Michael McNicholas, Eleonora Moroncini, Emmanuel Darcq, Marina Ter-Stepanian, Marie-Eve Fortier, Natalie Grizenko, Ridha Joober, Brigitte L. Kieffer
Summary: Both animal and human studies suggest that GPR88 is involved in Attention-Deficit/Hyperactivity Disorder (ADHD). Studies using Gpr88 knockout mice revealed ADHD-like behaviors, including increased motor impulsivity, reduced attention, and hyperactivity. The ADHD drug Atomoxetine reduced impulsivity in these mutant mice. Human genetic studies found associations between GPR88 variants and ADHD diagnosis, treatment response, and cognition, particularly in the presence of prenatal stress. Overall, GPR88 signaling appears to be a key factor in the diagnosis and treatment of ADHD.
MOLECULAR PSYCHIATRY
(2022)
Article
Chemistry, Medicinal
Ann M. Decker, Md Toufiqur Rahman, Chad M. Kormos, David Hesk, Emmanuel Darcq, Brigitte L. Kieffer, Chunyang Jin
Summary: This study synthesized and characterized the first GPR88 radio-ligand, [3H]RTI-33, derived from a synthetic agonist RTI-13951-33. [3H]RTI-33 showed specific and saturable binding (KD of 85 nM) in membranes prepared from stable PPLS-HA-hGPR88-CHO cells, and a competition binding assay was developed to determine binding affinities of several known GPR88 agonists. This radioligand represents a powerful tool for future mechanistic and cell-based ligand-receptor interaction studies of GPR88.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Neurosciences
Emmanuel Darcq, Dominique Nouel, Giovanni Hernandez, Matthew Pokinko, Polina Ash, Luc Moquin, Alain Gratton, Brigitte Kieffer, Cecilia Flores
Summary: The protective effects of Dcc haploinsufficiency against the rewarding effects of stimulant drugs do not extend to opioids and ethanol, suggesting different brain circuits mediate the rewarding effects of these substances.
PSYCHOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Florence Allain, Michelle Carter, Sylvie Dumas, Emmanuel Darcq, Brigitte L. Kieffer
Summary: The mu opioid receptor (MOR) and the orphan GPR151 receptor in the habenula are found to play important roles in social behaviors, and their absence leads to impaired social interactions in mice.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Lola Welsch, Esther Colantonio, Mathilde Frison, Desiree A. Johnson, Shannan P. Mcclain, Victor Mathis, Matthew R. Banghart, Sami Ben Hamida, Emmanuel Darcq, Brigitte L. Kieffer
Summary: This study found that μ opioid receptor neurons in the dorsal raphe nucleus (DRN) participate in reward and emotional responses. These neurons respond to rewarding stimuli and their optoactivation has reinforcing effects and promotes positive emotional responses. Furthermore, their effects are partially mediated by their projections to the lateral hypothalamus.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Chemistry, Medicinal
Md Toufiqur Rahman, Ann M. Decker, Sami Ben Hamida, David A. Perrey, Hetti Handi Chaminda Lakmal, Rangan Maitra, Emmanuel Darcq, Brigitte L. Kieffer, Chunyang Jin
Summary: We reported a new GPR88 agonist, RTI-122, with high potency and good metabolic stability, which could improve alcohol drinking behavior. This suggests that RTI-122 may serve as a promising lead compound for GPR88 agonist drug discovery research.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Wei Wang, Xueyi Xie, Xiaowen Zhuang, Yufei Huang, Tao Tan, Himanshu Gangal, Zhenbo Huang, William Purvines, Xuehua Wang, Alexander Stefanov, Ruifeng Chen, Lucas Rodriggs, Anita Chaiprasert, Emily Yu, Valerie Vierkant, Michelle Hook, Yun Huang, Emmanuel Darcq, Jun Wang
Summary: Withdrawal from chronic opioid use leads to hypodopaminergic states and negative affect, promoting relapse. Activation of MORs in dMSNs in the striatal patch compartment suppresses striatopallidal transmission, and withdrawal potentiated this transmission. Fentanyl self-administration enhances striatonigral transmission and reduces dopaminergic activity, while activated striatal neurons mediate contextual memory retrieval. Inhibition of striatal MOR+ neurons rescues fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These findings suggest that chronic opioid use induces GABAergic striatopallidal and striatonigral plasticity, leading to hypodopaminergic states and relapse.
Article
Psychiatry
Florence Allain, Aliza T. Ehrlich, Michael McNicholas, Florence Gross, Weiya Ma, Brigitte L. Kieffer, Emmanuel Darcq
Summary: This study found that the antidepressant tianeptine mainly exerts its effects on the brain through the μ-opioid receptor, and it exhibits analgesic, locomotor, and rewarding behaviors in animal models. These effects can only be observed in mice with positive expression of the opioid receptor, and are ineffective in mice with negative expression. In addition, chronic use of tianeptine may lead to tolerance to its analgesic and hyperlocomotor effects.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Neurosciences
Dersu Ozdemir, Florence Allain, Brigitte L. Kieffer, Emmanuel Darcq
Summary: Opioid use disorder is a chronic brain disease caused by long-term neuroadaptations resulting from repeated opioid consumption and withdrawal. These neuroadaptations lead to negative affect and various symptoms, such as loss of motivation, anxiety, social deficits, heightened stress reactivity, emotional and physical pain, dysphoria, sleep disorders, and chronic irritability. Understanding the neurocircuitry involved in withdrawal and abstinence is crucial for treatment and relapse prevention.
Article
Neurosciences
Lola Welsch, Esther Colantonio, Camille Falconnier, Cedric Champagnol-DiLiberti, Florence Allain, Sami Ben Hamida, Emmanuel Darcq, Pierre-Eric Lutz, Brigitte L. Kieffer
Summary: Chronic morphine abstinence leads to reduced MOR function in DRN-MOR neurons and abnormal self-stimulation, which may increase propensity for addiction-related behaviors.
BIOLOGICAL PSYCHIATRY
(2023)