Article
Biochemistry & Molecular Biology
Yongsheng Zhu, Peng Yan, Rui Wang, Jianghua Lai, Hua Tang, Xu Xiao, Rongshan Yu, Xiaorui Bao, Feng Zhu, Kena Wang, Ye Lu, Jie Dang, Chao Zhu, Rui Zhang, Wei Dang, Bao Zhang, Quanze Fu, Qian Zhang, Chongao Kang, Yujie Chen, Xiaoyu Chen, Qing Liang, Kejia Wang
Summary: Dysregulation of the immune system is a key factor in opioid addiction. The abnormal distribution of immune cells, particularly the expansion of fragile-like regulatory T cells (Tregs), is correlated with withdrawal symptoms. Opioids increase the expression of neuron-derived Ccl2, which disrupts the blood-brain barrier (BBB) integrity and allows Tregs to infiltrate the NAc, leading to synaptic instability and withdrawal symptoms mediated by IFN-y.
Article
Neurosciences
Sonia Aroni, Valeria Serra, Marco Bortolato, Roberto Frau, Miriam Melis
Summary: Vulnerability to cocaine use disorder is influenced by a combination of genetic and environmental factors. This study focuses on the interaction between allelic variants of the MAOA gene and early life stress (ES) in predisposition to cocaine abuse. The results demonstrate that the combination of low-activity alleles of the MAOA gene and ES increases sensitivity to cocaine's effects on dopamine neurons and impairs GABA synaptic efficacy. Additionally, the activation of dopamine D2 and CB1 receptors plays a role in the expression of these effects. The findings contribute to our understanding of the neural mechanisms underlying vulnerability to early onset cocaine use.
Article
Cell Biology
Xin He, Yue Xie, Qiongping Zheng, Zeyu Zhang, Shanshan Ma, Junyu Li, Mingtao Li, Qiaoying Huang
Summary: The transcription factor TFE3 has been found to play a crucial role in maintaining autophagy and the survival of dopaminergic neurons in Parkinson's disease. Activation of TFE3 may serve as a promising strategy for PD therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Miguel Skirzewski, Oren Princz-Lebel, Liliana German-Castelan, Alycia M. Crooks, Gerard Kyungwook Kim, Sophie Henke Tarnow, Amy Reichelt, Sara Memar, Daniel Palmer, Yulong Li, R. Jane Rylett, Lisa M. Saksida, Vania F. Prado, Marco A. M. Prado, Timothy J. Bussey
Summary: The study reveals that the acetylcholine-dopamine signaling in the nucleus accumbens is continuously updated to regulate the neuronal output involved in Pavlovian approach learning.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Simeng Wang, Qingzhang Zhu, Guosheng Liang, Tania Franks, Magalie Boucher, Kendra K. Bence, Mingjian Lu, Carlos M. Castorena, Shangang Zhao, Joel K. Elmquist, Philipp E. Scherer, Jay D. Horton
Summary: Studies using mice lacking CB-1 in hepatocytes or stellate cells suggest that CB-1 signaling does not directly contribute to the development of NAFLD or liver fibrosis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Mary Tresa Zanda, Gabriele Floris, Stephanie E. Sillivan
Summary: This study found that the dosage of drugs and discriminative drug cues have different effects on the incubation of opioid craving, while the drug intake history also plays a role in the time-dependent drug-seeking.
SCIENTIFIC REPORTS
(2021)
Article
Mathematics, Applied
Tom Chou, Maria R. D'Orsogna
Summary: This study proposes a simple and easily interpretable dynamical systems model to describe the neurobiology of drug addiction, incorporating the concepts of reward prediction error, drug-induced incentive salience, and opponent process theory. The model suggests that drug-induced dopamine releases activate biphasic reward responses, and neuroadaptive processes triggered by successive intakes enhance the negative component, leading to habituation and addiction. The study finds that individuals with a strong negative process response to drug consumption are most at risk for addiction. Possible mechanisms to mitigate withdrawal symptoms are also discussed.
Article
Neurosciences
Angel Juan Garcia-Yague, Isabel Lastres-Becker, Leonidas Stefanis, Demetrios K. Vassilatis, Antonio Cuadrado
Summary: This study provides a mechanistic explanation for the downregulation of NURR1 by alpha-synuclein in Parkinson's disease, connecting it to GSK-3 induced phosphorylation and proteasomal degradation. The identified domain targeted by GSK-3 for NURR1 ubiquitination and degradation sheds light on the regulation of NURR1 stability in synucleinopathies.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Psychiatry
Ditte Olsen, Niels Wellner, Mathias Kaas, Inge E. M. de Jong, Florence Sotty, Michael Didriksen, Simon Glerup, Anders Nykjaer
Summary: Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder worldwide, and Sorcs2(-/-) mice can replicate symptoms reminiscent of ADHD. Research shows that loss of the SorCS2 gene affects dopaminergic circuit function and behavioral responses to the environment.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ichiro Kawahata, Tomoki Sekimori, Haoyang Wang, Yanyan Wang, Toshikuni Sasaoka, Luc Bousset, Ronald Melki, Tomohiro Mizobata, Yasushi Kawata, Kohji Fukunaga
Summary: The study showed that dopamine D-2L receptors combined with FABP3 play a critical role in the uptake of alpha-synuclein by dopaminergic neurons. This finding suggests a novel pathogenic mechanism for synucleinopathies, including Parkinson's disease.
Article
Neurosciences
Kevin T. Ball, Hunter Edson
Summary: It has been found that male rats are less sensitive to punishment during cocaine self-administration compared to females. Additionally, daily restraint stress increases sensitivity to punishment in males but has no effect on females. This study aimed to determine whether chronic stress-induced dopamine release in the prelimbic medial prefrontal cortex mediates the effect of stress on punished cocaine self-administration.
NEUROSCIENCE LETTERS
(2023)
Article
Neurosciences
Yu Chen, Yuhui Jiang, Yinuo Yang, Xinzhong Huang, Cheng Sun
Summary: The study revealed that SIRT1 has neuroprotective effects on dopaminergic neurons by promoting cell survival, maintaining mitochondrial function, and reducing cell apoptosis. These effects are dependent on SIRT1-mediated mitochondrial biogenesis via PGC-1α, suggesting great therapeutic potential of SIRT1 for disorders associated with dopaminergic neuron loss such as PD.
NEUROTOXICITY RESEARCH
(2021)
Article
Immunology
Daniel Torrente, Enming J. Su, Gerald P. Schielke, Mark Warnock, Kris Mann, Daniel A. Lawrence
Summary: NE depletion causes degeneration of dopaminergic neurons in the PD model, and β2-adrenergic receptor (AR) agonists may have therapeutic potential in the context of α-SYN-driven neuropathology.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Nolan M. Dvorak, Jessica Di Re, Tileena E. S. Vasquez, Mate Marosi, Poonam Shah, Yorkiris M. Marmol Contreras, Matteo Bernabucci, Aditya K. Singh, Jariatu Stallone, Thomas A. Green, Fernanda Laezza
Summary: Cocaine use disorder (CUD) is a prevalent neuropsychiatric disorder with limited treatment options. This study identified fibroblast growth factor 13 (FGF13) as a potential pharmacological target for CUD, as it regulates the activity of Na+ channels and protects against cocaine self-administration.
FRONTIERS IN NEUROSCIENCE
(2023)
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
Clinical Neurology
Ya-Hsien Huang, Ming Tatt Lee, Han-Yun Hsueh, Daniel E. Knutson, James Cook, Marko D. Mihovilovic, Werner Sieghart, Lih-Chu Chiou
Summary: Ethanol has been shown to suppress essential tremor (ET) in patients at low-to-moderate doses, but its mechanism(s) of action remain unknown. One potential mechanism is the positive allosteric modulation of alpha 6GABA(A)Rs by ethanol, which may attenuate tremor activity.
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
Clinical Neurology
Jung-Chieh Du, Man-Hsin Chang, Chen-Jiun Yeh, Ming Tatt Lee, Hsin-Jung Lee, Shu-Hui Chuang, Lih-Chu Chiou
Summary: The SLITRK1 gene mutation and loss of striatal cholinergic interneurons (ChIs) are associated with Tourette syndrome (TS). In a mouse model, Slitrk1-KD mice exhibited TS-like tic behaviors, impaired prepulse inhibition, and delayed sensorimotor response. These characteristics were correlated with lower levels of striatal Slitrk1 protein, fewer Slitrk1-containing ChIs, and fewer activated ChIs in Slitrk1-KD mice.
ANNALS OF NEUROLOGY
(2023)
Article
Plant Sciences
Tin-Yun Ho, Hsin-Yi Lo, Guan-Ling Lu, Pei-Yung Liao, Chien-Yun Hsiang
Summary: This study used bioluminescent imaging and gene expression profiling to demonstrate, for the first time, that Houttuynia cordata has lung meridian-guiding effects and exhibits potent anti-inflammatory potential in the upper respiratory tract. The NF-κB and IL-18 pathways are associated with the anti-inflammatory mechanism of Houttuynia cordata against LPS-induced airway inflammation. Additionally, chlorogenic acid and quercitrin may be involved in the anti-inflammatory properties of Houttuynia cordata.
JOURNAL OF ETHNOPHARMACOLOGY
(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.
Correction
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Article
Plant Sciences
Chien-Yun Hsiang, Hsin-Yi Lo, Guan-Ling Lu, Pei-Yung Liao, Tin-Yun Ho
Summary: This study identified a novel heat-stable ACE inhibitory peptide, CS-1, in corn silk extract. CS-1 interacted with the zinc-binding motif of ACE, leading to the inhibition of ACE activity and a subsequent decrease in blood pressure in rats.
JOURNAL OF ETHNOPHARMACOLOGY
(2024)
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)