Article
Pharmacology & Pharmacy
Keith M. Olson, Andrea L. Devereaux, Payal Chatterjee, Savanah L. Saldana-Shumaker, Amanda Shafer, Adam Plotkin, Ram Kandasamy, Alexander D. MacKerell, John R. Traynor, Christopher W. Cunningham
Summary: This study investigates the structure-activity relationships of benzylideneoxymorphone analogs in order to develop analgesics with reduced tolerance and side effects. One compound, nitro-BOM (NBOM), showed high-efficacy antinociception but also exhibited tolerance and toxicity upon repeated administration. Despite these issues, NBOM provides an important tool for understanding MOPr/DOPr pharmacology.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Anesthesiology
Akane Komatsu, Kanako Miyano, Daisuke Nakayama, Yusuke Mizobuchi, Eiko Uezono, Kaori Ohshima, Yusuke Karasawa, Yui Kuroda, Miki Nonaka, Keisuke Yamaguchi, Masako Iseki, Yasuhito Uezono, Masakazu Hayashida
Summary: The compounds N1 and N2 have high transdermal absorbability and equivalent analgesic effects as morphine. They may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.
ANESTHESIA AND ANALGESIA
(2022)
Review
Geriatrics & Gerontology
Yuan Xu, Ronghua Chen, Feng Zhi, Shiying Sheng, Leena Khiati, Yilin Yang, Ya Peng, Ying Xia
Summary: Neuroinflammation is the underlying cause of many age-related neurological disorders, and microglia play a crucial role in regulating neuroinflammation and neuronal survival. Recent studies have shown that activation of the δ-opioid receptor (DOR) can protect neurons by inhibiting microglial inflammation. In contrast, inhibiting DOR or reducing its activity can promote microglial activation and worsen cell injury. This finding suggests that targeting microglia through modulation of neuroinflammation by DOR has therapeutic potential for age-related neurological disorders.
Article
Neurosciences
Josue Jaramillo-Polanco, Cintya Lopez-Lopez, Yang Yu, Emma Neary, Alan Hegron, Meritxell Canals, Nigel W. Bunnett, David E. Reed, Alan E. Lomax, Stephen J. Vanner
Summary: This study found that chronic high-dose opioid exposure leads to opioid-induced hyperalgesia (OIH) in the gastrointestinal tract, which is mediated by DOPr signaling and dependent on receptor endocytosis and protein kinase C signaling.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
David Reiss, Herve Maurin, Emilie Audouard, Miriam Martinez-Navarro, Yaping Xue, Yann Herault, Rafael Maldonado, David Cabanero, Claire Gaveriaux-Ruff
Summary: The study found that astrocytic DOR plays a significant role in promoting cold allodynia and analgesic tolerance in females, while overall DOR activity is protective. DOR activity in astrocytes exacerbates neuropathic allodynia, while DOR activity in other cells attenuates this form of pain.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Zachary W. Reichenbach, Kelly DiMattio, Suren Rajakaruna, David Ambrose, William D. Cornwell, Ronald J. Tallarida, Thomas Rogers, Lee-Yuan Liu-Chen, Ronald F. Tuma, Sara Jane Ward
Summary: Non-selective cannabinoid (CB) agonists can enhance the analgesic effects of morphine but inhibit its antinociceptive tolerance. Activation of CB2 receptors can reverse allodynia and hyperalgesia in chronic pain models, and co-administration of CB2 receptor selective agonists with morphine can synergistically enhance the effects. However, the interactions between CB2 receptor selective agonist O-1966 and morphine depend on the order of administration.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Geriatrics & Gerontology
Yuan Xu, Feng Zhi, Ya Peng, Jiahao Mao, Gianfranco Balboni, Yilin Yang, Ying Xia
Summary: Microglia play an important role in regulating cerebral homeostasis and combating pathogens. Excessive activation of microglia has been implicated in various age-related cerebral diseases. Microglia can undergo complex polarization changes, which can exacerbate or alleviate cellular injury. Delta-opioid receptor (DOR) activation has a protective effect against neuronal injuries, and our study suggests that DOR expression/function is closely linked to microglial polarization and plays a critical role in controlling microglial activation. These findings provide new insights into protective strategies against neurodegenerative pathologies through DOR-mediated regulation of microglia.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Osamu Nakagawasai, Kohei Takahashi, Akihiro Ambo, Kentaro Onuma, Naruya Takahashi, Wataru Nemoto, Koichi Tan-No
Summary: Delta opioid receptors are proposed as important targets for developing novel antidepressants. Deltorphin analogs have shown antidepressant-like effects by activating the central delta(1) opioid receptor in mice and reducing immobility behavior.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Behavioral Sciences
Luke A. Jelen, James M. Stone, Allan H. Young, Mitul A. Mehta
Summary: This article reviews the dysregulation of the opioid system in depression and the potential of pharmacological modulators of mu, delta, and kappa opioid receptors for the treatment of depression. The review presents evidence from animal and clinical studies supporting the dysregulation of the opioid system in depression, the modulation of behavioral processes and brain regions associated with depression by opioids, and the modulation of antidepressant responses by opioids. The review also evaluates clinical trials examining the safety and efficacy of opioidergic agents in depression and explores the involvement of the opioid system in the effects of other treatments, such as ketamine, that exert antidepressant effects through non-opioid actions. Furthermore, the review explores the neurochemical and molecular mechanisms underlying the therapeutic effects of opioid system engagement, providing a rationale for further investigation into this relevant target in depression treatment.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Neurosciences
Volker Neugebauer, Peyton Presto, Vadim Yakhnitsa, Nico Antenucci, Brianna Mendoza, Guangchen Ji
Summary: Neuroplasticity in cortico-limbic circuits is important in pain persistence and modulation. The amygdala plays a key role in the emotional dimension of pain, and interactions with prefrontal cortical regions change in pain conditions. Other regions in the limbic system are also involved in pain modulation. The corticolimbic system contains opioids and opioid receptors, and their modulatory effects and potential opposing functions are still not fully understood.
Review
Biochemistry & Molecular Biology
Lin Li, Jing Chen, Yun-Qing Li
Summary: Neuropathic pain (NP) is a type of pain caused by damage or malfunction of the peripheral or central nervous system. It affects the physical and mental health of 7-10% of the general population. This literature review focuses on the role of downregulation of opioid receptors in the development of NP, particularly from the perspective of dorsal root ganglion, spinal cord, and supraspinal regions. The review also discusses the reasons for the poor efficacy of opioids in NP treatment, including opioid tolerance caused by NP and repeated opioid treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Geriatrics & Gerontology
Yimeng Chen, Yichen He, Shuchen Zhao, Xiaozhou He, Dong Xue, Ying Xia
Summary: Hypoxia and ischemia play a critical role in the pathogenesis of various diseases in different organs. However, protective strategies against hypoxic and ischemic insults are limited in clinical settings. Recent studies have shown that microRNAs and delta-opioid receptors are differentially altered in response to hypoxic and ischemic stress and contribute to the protection against inflammatory injury. This review summarizes the findings from recent studies and discusses the potential impact of delta-opioid receptors on miRNA expression and inflammatory injury in different organs.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Aina Porta, Laura Rodriguez, Xue Bai, Gerard Batalle, Gerad Roch, Enric Pouso-Vazquez, Gianfranco Balboni, Olga Pol
Summary: This study demonstrates that slow-releasing H2S donors can inhibit allodynia and hyperalgesia, potentiate the analgesic effects and expression of DOR, activate the antioxidant system, and reduce nociceptive and apoptotic pathways in inflammatory pain models. The data also suggest the involvement of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. Systemic administration of DADS and P-ITC, along with local application of DOR agonists in combination with H2S donors, offer new strategies for the treatment of inflammatory pain.
Article
Chemistry, Medicinal
Madeline R. Hennessy, Anna M. Gutridge, Alexander R. French, Elizabeth S. Rhoda, Yazan J. Meqbil, Meghna Gill, Yavnika Kashyap, Kevin Appourchaux, Barnali Paul, Zaijie Jim Wang, Richard M. van Rijn, Andrew P. Riley
Summary: Akuammine and pseudoakuammigine are indole alkaloids derived from the seeds of the akuamma tree. They act as weak agonists of the mu opioid receptor and show minimal effects in animal models of antinociception. By synthesizing 22 semisynthetic derivatives and evaluating their activity at the mu opioid receptor and kappa opioid receptor, we identified derivatives with improved potency at the mu opioid receptor.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Henry R. Kranzler, Kevin G. Lynch, Richard C. Crist, Emily Hartwell, Anne Le Moigne, Celine M. Laffont, Anne C. Andorn
Summary: This study examined the moderating effect of the rs678849 gene on the response to BUP-XR treatment in different ethnicities with OUD. The results showed a significant impact of the rs678849 gene on the treatment response in European Americans, but not in African Americans.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Tom Willemse, Emilie Eiselt, Karlijn Hollanders, Wim Schepens, Herman W. T. van Vlijmen, Nga N. Chung, Veronique Blais, Brain Holleran, Jean-Michel Longpre, Peter W. Schiller, Bert U. W. Maes, Philippe Sarret, Louis Gendron, Steven Ballet
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Biochemistry & Molecular Biology
Jean-Louis Beaudeau, Veronique Blais, Brian J. Holleran, Alexandre Bergeron, Graciela Pineyro, Brigitte Guerin, Louis Gendron, Yves L. Dory
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Pharmacology & Pharmacy
Emilie Eiselt, Jerome Cote, Jean-Michel Longpre, Veronique Blais, Philippe Sarret, Louis Gendron
EUROPEAN JOURNAL OF PHARMACOLOGY
(2019)
Article
Pharmacology & Pharmacy
Louisane Desbiens, Catherine Lapointe, Louis Gendron, Marjan Gharagozloo, Laurence Vincent, Gunnar Pejler, Denis Gris, Pedro D'Orleans-Juste
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Biochemistry & Molecular Biology
Marjan Gharagozloo, Shaimaa Mahmoud, Camille Simard, Kenzo Yamamoto, Diwakar Bobbala, Subburaj Ilangumaran, Matthew D. Smith, Albert Lamontagne, Samir Jarjoura, Jean-Bernard Denault, Veronique Blais, Louis Gendron, Caries Vilarino-Guell, A. Dessa Sadovnick, Jenny P. Ting, Peter A. Calabresi, Abdelaziz Amrani, Denis Gris
Article
Biochemistry & Molecular Biology
Emilie Eiselt, Simon Gonzalez, Charlotte Martin, Magali Chartier, Cecilia Betti, Jean-Michel Longpre, Florine Cavelier, Dirk Tourwe, Louis Gendron, Steven Ballet, Philippe Sarret
ACS CHEMICAL NEUROSCIENCE
(2019)
Review
Clinical Neurology
Sophie Berthiaume, Khaled Abdallah, Veronique Blais, Louis Gendron
JOURNAL OF NEURAL TRANSMISSION
(2020)
Article
Pharmacology & Pharmacy
Emilie Eiselt, Valerie Otis, Karine Belleville, Gaoqiang Yang, Alain Larocque, Anthony Regina, Michel Demeule, Philippe Sarret, Louis Gendron
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Review
Neurosciences
Jade Degrandmaison, Olivier Grise, Jean-Luc Parent, Louis Gendron
Summary: Recent studies have highlighted DOPr as a promising therapeutic target for chronic pain management, with its specific agonists exhibiting effective analgesic responses in various animal models. Despite high homology with other opioid receptors, DOPr displays significant particularities in its molecular regulation and trafficking mechanisms. These specific amino acid motifs potentially play a crucial role in determining the receptor's trafficking and physiological responses.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Beatrice Quirion, Claudie Beaulieu, Laurie Cote, Jean-Luc Parent, Louis Gendron
Summary: This study aimed to assess the distribution of MOP and DOP in the dorsal root ganglia of mice and rats. The results showed that both receptors are expressed in all types of neurons to different extents. DOP is mainly expressed in large and medium myelinated neurons, while MOP is mainly found in C fibres. The distribution slightly differs between rats and mice.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Niousha Nazari, Sylvain Bernard, Daniel Fortin, Thomas Marmin, Louis Gendron, Yves L. Dory
Summary: Three C-3 symmetric macrolactams were efficiently cyclized from linear precursors by properly locating substituents, resulting in enhanced reactivity compared to the unsubstituted parent. DFT calculations showed that the reactive conformer, the properly folded cyclization precursor, was more populated than other conformers, leading to a decrease in the activation free energy. The crystal structure of the ester-substituted ring with three bulky esters revealed the preservation of tubular stacking.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Neurosciences
Charly G. Lecomte, Stephen Mari, Johannie Audet, Angele N. Merlet, Jonathan Harnie, Claudie Beaulieu, Khaled Abdallah, Louis Gendron, Ilya A. Rybak, Boris I. Prilutsky, Alain Frigon
Summary: This study investigates the recovery of locomotion in animals and people with incomplete spinal cord injury (SCI) in left-right asymmetric conditions. The results show that adjustments in kinematics and muscle activity allow individuals with incomplete SCI to retain the ability to perform asymmetric locomotion.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Neurosciences
Johannie Audet, Sirine Yassine, Charly G. Lecomte, Stephen Mari, Felix Soucy, Caroline Morency, Angele N. Merlet, Jonathan Harnie, Claudie Beaulieu, Louis Gendron, Ilya A. Rybak, Boris I. Prilutsky, Alain Frigon
Summary: Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the forelimbs and hindlimbs. Spinal cord injury (SCI) disrupts these pathways. Cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one. Coordination between the forelimbs and hindlimbs displays 2:1 patterns and becomes weaker and more variable after both hemisections.
Article
Biochemistry & Molecular Biology
Dominique Bella Ndong, Veronique Blais, Brian J. Holleran, Arnaud Proteau-Gagne, Isabelle Cantin-Savoie, William Robert, Jean-Francois Nadon, Sophie Beauchemin, Richard Leduc, Graciela Pineyro, Brigitte Guerin, Louis Gendron, Yves L. Dory
Article
Biochemistry & Molecular Biology
Iness Charfi, Khaled Abdallah, Louis Gendron, Graciela Pineyro
CELLULAR AND MOLECULAR LIFE SCIENCES
(2018)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.