Review
Physiology
Krystyna Pierzchala-Koziec, Colin G. Scanes
Summary: The review explores the presence of potential hormonal opioid peptides in birds and other vertebrates. It identifies four opioid-related genes, which encode a series of peptides: proenkephalin (PENK), prodynorphin (PDYN), pronociceptin (PNOC), and proopiomelanocortin (POMC). These genes produce various opioid peptides with distinct physiological roles and effects, including pain modulation and growth/development. The study highlights the need for further research to understand the specific biological functions, interactions, and processing of these peptides in different tissues, especially in avian species.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Adrian Martyniak, Andrzej Wedrychowicz, Przemyslaw J. Tomasik
Summary: Caring for patients with Crohn's disease is a serious challenge, and new methods of diagnosis and therapy are needed. Endogenous opioids, such as β-endorphin and proenkephalin (A), may have beneficial effects on the disease. This study found that the concentrations of these endo-opioids were reduced in CD patients, suggesting modulation of the endogenous opioid system as a promising future treatment for CD.
Article
Pharmacology & Pharmacy
Kevin Clare, Chelsea Pan, Gloria Kim, Kicheon Park, Juan Zhao, Nora D. Volkow, Zhicheng Lin, Congwu Du
Summary: The study revealed increased density of D2r-positive cells in the medial prefrontal cortex and ventral tegmental area of both male and female mice passively exposed to chronic cocaine, alongside an overall decrease in neuronal density. Higher levels of Drd2 mRNA in the mPFC and Dstr of female mice exposed to cocaine suggest limited sensitivity of the method used. This shift in neuronal phenotype and potential cognitive impairments warrant further investigation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Fu-Jun Zhai, Song-Ping Han, Tian-Jia Song, Ran Huo, Xing-Yu Lan, Rong Zhang, Ji-Sheng Han
Summary: The analgesic effect of spinal cord stimulation (SCS) in a spared nerve injury model was characterized and its underlying mechanisms were examined. Different frequencies of SCS were found to mediate analgesic effects through different endorphins and opioid receptors.
NEUROSCIENCE BULLETIN
(2022)
Article
Medicine, General & Internal
Miriam M. Duell, Katharina Wolf, Marcel Vetter, Peter Dietrich, Markus F. Neurath, Andreas E. Kremer
Summary: This study investigated the levels of important endogenous opioids in patients with immune-mediated hepatobiliary disorders and found that they do not correlate with itch intensity or differentiate pruritic from non-pruritic patients. This suggests that endogenous opioids may modulate signaling pathways involved in hepatic pruritus, but are unlikely to represent the major pruritogens in liver disease.
FRONTIERS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
A. F. Garcia, E. A. Crummy, I. G. Webb, M. N. Nooney, S. M. Ferguson
Summary: Processing within the anterior cingulate cortex is crucial for appropriate behavior, and dysfunction following chronic drug use is thought to play a major role in drug addiction. Two types of cortical pyramidal projection neurons regulate distinct features of a drug experience, its positive and negative aspects, respectively, supporting a revised theory of cortical function in addiction.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Manuel Lisardo Sanchez, Francisco D. D. Rodriguez, Rafael Covenas
Summary: Peptides play a crucial role in cancer progression, promoting mitogenesis, migration, invasion, metastasis, and anti-apoptotic mechanisms. Peptide receptors are overexpressed in tumor cells, making them potential targets for specific cancer treatments and apoptosis induction. Opioids have both anti-tumoral and pro-tumoral effects, and their involvement in cancer development is still not well understood.
Article
Neurosciences
Mitchell R. Farrell, Jeanine Sandra D. Esteban, Lauren Faget, Stan B. Floresco, Thomas S. Hnasko, Stephen V. Mahler
Summary: Through chemogenetic inhibition of VPGABA neurons, it has been demonstrated that these neurons play a critical role in high-stakes decision-making, leading rats to prefer a safe small reward over a risky large reward.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Kanako Matsumura, Amelia Nicot, In Bae Choi, Meera Asokan, Nathan N. Le, Luis A. Natividad, Lauren K. Dobbs
Summary: Cocaine cues and contexts strongly influence behavior and can promote cocaine seeking and taking. These behaviors are encoded in striatal circuits and regulated by opioid peptides and receptors in medium spiny neurons. The role of striatal enkephalin in the acquisition and extinction of cocaine conditioned behavior is not necessary, but other opioid peptides may be involved, especially in females.
Article
Multidisciplinary Sciences
Lizhu Li, Lihui Lu, Yuqi Ren, Guo Tang, Yu Zhao, Xue Cai, Zhao Shi, He Ding, Changbo Liu, Dali Cheng, Yang Xie, Huachun Wang, Xin Fu, Lan Yin, Minmin Luo, Xing Sheng
Summary: In this study, a wireless, dual-color optogenetic probe with the co-expression of two spectrally distinct opsins was used to achieve bidirectional neuronal activity manipulation in a rodent model. The probe showed colocalized red and blue emissions and enabled chronic in vivo operations. It could interfere with dopaminergic neurons, resulting in different behaviors and social interactions among mice.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Giuseppe Tringali, Gianluca Lavanco, Valentina Castelli, Giuseppe Pizzolanti, Martin Kuchar, Diego Curro, Carla Cannizzaro, Anna Brancato
Summary: Alcohol binge drinking in adolescents affects the CGRP signalling system, causing abnormal behavior and hormone secretion. Using a rat model, the study found that cannabidiol (CBD) could reduce alcohol consumption and rebalance the bio-behavioral abnormalities caused by binge drinking.
PHYTOTHERAPY RESEARCH
(2023)
Article
Neurosciences
Jicheng Li, Renfei Fan, Xiaofeng Liu, Xiangfeng Shen, Xin Liu, Hua Zhao
Summary: The study found that most neurons in LHb are aversion-activated and reward-inhibited, mainly composed of glutamatergic neurons, while most neurons in VTA are reward-activated and aversion-inhibited, inhibited by glutamatergic neurons in LHb. Optogenetic activation or inhibition of glutamatergic neurons in LHb and their terminals in VTA could induce aversive or reward behaviors.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biology
Kali Esancy, Lais L. Conceicao, Andrew Curtright, Thanh Tran, Logan Condon, Bryce Lecamp, Ajay Dhaka
Summary: Pain is one of the main reasons for seeking medical care, but current analgesics are often ineffective or have undesirable side effects. A small molecule called AS1 was discovered through a behavioral screen in larval zebrafish, which surprisingly elicited attraction to noxious heat. Further experiments showed that AS1 can reverse the negative valence of both painful and non-painful aversive stimuli without being rewarding. The mechanism of AS1 involves the activation of D1 dopamine receptor pathways.
Article
Economics
Qianwen Li, Tingyu Qian, Xufeng Zhang, Ruyin Long, Hong Chen, Han Huang, Lei Liu, Licai Zhu, Huikang Jiang, Hanyi Zhu
Summary: This study incorporates loss aversion psychology and an evolutionary game model to analyze the factors and policy implications of green housing development, considering the perspectives of the government, realtors, and residents.
ECONOMIC ANALYSIS AND POLICY
(2023)
Review
Neurosciences
Johannes W. de Jong, Kurt M. Fraser, Stephan Lammel
Summary: Ventral tegmental area dopamine neurons encode reward prediction errors, but their release in the nucleus accumbens is involved in reinforcement learning, motivation, aversion, and incentive salience. The contrast between the homogeneous role of dopamine neuron activity and the heterogeneous functions of dopamine release raises questions about how VTA dopamine activity translates into NAc dopamine release.
ANNUAL REVIEW OF NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Ming Tatt Lee, Ken Mackie, Lih-Chu Chiou
Summary: This review explores the potential and contributions of activating the endocannabinoid system and peripheral neuromodulation in opioid tolerance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Dora Kovari, Veronika Penksza, Anett Szilvasy-Szabo, Richard Sinko, Balazs Gereben, Ken Mackie, Csaba Fekete
Summary: Tanycytes regulate the hypothalamic-pituitary-thyroid axis by modulating local thyroid hormone availability and inhibiting TRH release. Decreased endocannabinoid release from tanycytes results in increased TSH synthesis, higher T4 levels, altered glucose homeostasis, and fat deposition.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Anesthesiology
Xiaoyan Lin, Zhili Xu, Lawrence Carey, Julian Romero, Alexandros Makriyannis, Cecilia J. Hillard, Elizabeth Ruggiero, Marilyn Dockum, George Houk, Ken Mackie, Phillip J. Albrecht, Frank L. Rice, Andrea G. Hohmann
Summary: This study investigated the cell types expressing CB2 receptor and found that CB2 expressed in previously unrecognized populations of skin cells may serve as a potential target for suppressing chemotherapy-induced neuropathic pain.
Article
Clinical Neurology
Amanda Seelman, Kristina Vu, Paul Buckmaster, Ken Mackie, Cara Field, Shawn Johnson, Megan Wyeth
Summary: Pathological changes, such as sclerosis, in the dentate gyrus are characteristic of temporal lobe epilepsy. In this condition, the inhibitory interneurons expressing parvalbumin decrease their perisomatic-targeting axonal boutons while the interneurons expressing somatostatin show exuberant sprouting of dendrite-targeting axonal boutons. The evidence regarding the cannabinoid receptor type 1 (CB1) expressing interneurons is conflicting, with unclear changes in their bouton numbers. A study on California sea lions with naturally occurring temporal lobe epilepsy, which shows similar neuroanatomy and neuropathology to humans, revealed a decrease in CB1-labeled boutons in sclerotic hippocampi compared to controls. However, the reduction in the number of granule cells was greater, resulting in an increased density of CB1-labeled boutons per granule cell in sclerotic hippocampi. This suggests enhanced innervation from CB1-expressing boutons in surviving cells of epileptic sea lions.
Article
Biochemistry & Molecular Biology
Michaela Dvorakova, Sierra Wilson, Wesley Corey, Jenna Billingsley, Anaelle Zimmowitch, Joye Tracey, Alex Straiker, Ken Mackie
Summary: In addition to phytocannabinoids, cannabis terpenoids may have various effects on the body. Testing them in two neuronal models, researchers found that only a small number of terpenoids had notable effects on cannabinoid signaling, particularly nerolidol.
Article
Pharmacology & Pharmacy
Lawrence M. Carey, Zhili Xu, Gabriela Rajic, Alexandros Makriyannis, Julian Romero, Cecilia Hillard, Ken Mackie, Andrea G. Hohmann
Summary: This study suggests that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identifies a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. The study also demonstrates that a CB2 agonist can reverse established morphine tolerance and shows that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Toni Kline, Cong Xu, Faith R. Kreitzer, Dow P. Hurst, Khalil M. Eldeeb, Jim Wager-Miller, Kathleen Olivas, Seon A. Hepburn, John W. Huffman, Ken Mackie, Allyn C. Howlett, Patricia Reggio, Nephi Stella
Summary: The author synthesized fourteen novel alkylindole analogues and evaluated their activities at alkylindole-sensitive GPCRs. They found three characteristics that favor binding to alkylindole-sensitive GPCRs versus CB1R/CB2R and identified novel chemical tools for studying alkylindole-sensitive GPCRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Jinhwan Lim, Hye-Lim Lee, Julie Nguyen, Joyce Shin, Samantha Getze, Caitlin Quach, Erica Squire, Kwang-Mook Jung, Stephen Mahler, Ken Mackie, Daniele Piomelli, Ulrike Luderer
Summary: Adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Further investigation is needed to understand the relevance of these findings to women who frequently used cannabis during adolescence.
TOXICOLOGICAL SCIENCES
(2023)
Article
Engineering, Biomedical
Hongwei Cai, Zheng Ao, Chunhui Tian, Zhuhao Wu, Connor Kaurich, Zi Chen, Mingxia Gu, Andrea G. Hohmann, Ken Mackie, Feng Guo
Summary: Opioids may induce tolerance and hyperalgesia, but the human mechanisms underlying these effects are not well understood. Researchers have developed a novel human spinal microphysiological system (MPS) to model human nociception and opioid-induced tolerance. This system shows promising potential for studying pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Jonah E. Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Cristina M. Youwakim, Kwangho Kim, Andrew N. Jenkins, Isabelle C. Suero, Margaret R. Jones, Zahra Mashhadi, Ken Mackie, Alex G. Waterson, Amanda C. Doran, Gary A. Sulikowski, Sean S. Davies
Summary: N-Acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is an enzyme that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acyl-ethanolamines (NAEs) and phosphatidic acid. Reduced NAPE-PLD activity is associated with cardiometabolic diseases, and small molecule activators of NAPE-PLD could be a potential therapeutic treatment. A series of benzothiazole phenylsulfonyl-piperidine carboxamides were identified as NAPE-PLD activators, which increased efferocytosis by macrophages. These findings suggest the importance of NAPE-PLD in regulating efferocytosis and the potential use of NAPE-PLD activators for treating cardiometabolic diseases.
ACS CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Kelsey G. Guenther, Zhili Xu, Julian Romero, Cecilia J. Hillard, Ken Mackie, Andrea G. Hohmann
Summary: CB2 agonists can suppress pathological pain in animal models without unwanted side effects associated with CB1 receptor activation. However, the specific types of pain responsive to CB2 agonists and the cell types underlying therapeutic efficacy are not fully understood.
Article
Pharmacology & Pharmacy
Axel Bernabeu, Anissa Bara, Michelle N. Murphy Green, Antonia Manduca, Jim Wager-Miller, Milene Borsoi, Olivier Lassalle, Anne-Laure Pelissier-Alicot, Pascale Chavis, Ken Mackie, Olivier J. J. Manzoni
Summary: This study reveals sex differences in the maturational trajectories of the rat prefrontal cortex (PFC). The excitability of PFC neurons is lower in adult females compared to other developmental stages. The gene expression of the endocannabinoid/vanilloid systems is sequential and sex-specific.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Correction
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Article
Pharmacology & Pharmacy
Pedro Henrique Gobira, Jacob LaMar, Jade Marques, Ariandra Sartim, Kennia Silveira, Luana Santos, Gregers Wegener, Francisco S. Guimaraes, Ken Mackie, Hui-Chen Lu, Samia Joca
Summary: This study investigates the involvement of cannabinoid type 1 receptors (CB1R) in the antidepressant and psychostimulant effects induced by ketamine. The results suggest that CB1R mediate the psychostimulant side effects of ketamine, but do not play a role in its antidepressant properties. Furthermore, pharmacological blockade of CB1R has similar antidepressant effects, but does not potentiate the effects of ketamine.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Joanna Winstone, Hana Shafique, Madeleine E. Clemmer, Ken Mackie, Jim Wager-Miller
Summary: This study found changes in BDNF mRNA expression in the hippocampus of adolescent mice exposed to THC and CBD. THC represses transcript expression for some BDNF variants, and this effect is rescued when CBD is co-administered. Sex differences were observed in specific BDNF isoforms.
CANNABIS AND CANNABINOID RESEARCH
(2023)
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.
