Article
Neurosciences
Douglas J. Hermes, Barkha J. Yadav-Samudrala, Changqing Xu, Jacqueline E. Paniccia, Rick B. Meeker, Michael L. Armstrong, Nichole Reisdorph, Benjamin F. Cravatt, Ken Mackie, Aron H. Lichtman, Bogna M. Ignatowska-Jankowska, Donald T. Lysle, Sylvia Fitting
Summary: This study investigated the role of FAAH inhibition in microglial neurotoxicity induced by HIV-1 Tat protein. The results demonstrated that the FAAH inhibitor PF3845 effectively attenuated the neurotoxic effects, leading to neuroprotection of neurons from damage.
EXPERIMENTAL NEUROLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Marianne Roca, James W. Lightfoot
Summary: Cannabinoids can increase the preference for calorific foods by promoting hedonic feeding behaviors. A new study investigates and characterizes these indulgent behaviors in the nematode Caenorhabditis elegans, providing insights into their regulatory mechanisms.
Article
Pharmacology & Pharmacy
Hebaallah Mamdouh Hashiesh, Niraj Kumar Jha, Charu Sharma, Piyush Kumar Gupta, Saurabh Kumar Jha, Chandragouda R. Patil, Sameer N. Goyal, Shreesh K. Ojha
Summary: The pharmacological activation of CB2R, particularly by the compound JWH133, has shown promising neuroprotective and anti-inflammatory effects in various neurological disorders, making it a potential candidate for drug development in neurotherapeutics. Further regulatory toxicology and pharmacokinetic studies are needed to evaluate its safety for clinical use.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Clinical Neurology
Astrid Coronado-Alvarez, Karen Romero-Cordero, Lorena Macias-Triana, Agnes Tatum-Kuri, Alba Vera-Barron, Henning Budde, Sergio Machado, Tetsuya Yamamoto, Claudio Imperatori, Eric Murillo-Rodriguez
Summary: Δ9-THC, the major component of Cannabis sativa, exerts biological effects through activation of cannabinoid receptors CB1 and CB2. Synthetic CB1 cannabinoid receptor selective agonists show potential in therapeutic approaches, but concerns regarding side effects still exist despite positive results in experimental models and preclinical trials.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Ophthalmology
Bindu Kodati, Dorota L. Stankowska, Vignesh R. Krishnamoorthy, Raghu R. Krishnamoorthy
Summary: The study found that JNK2 plays a major role in endothelin-mediated loss of retinal ganglion cells in mice. The neuroprotective effects in JNK2(-/-) mice following ET-1 administration occur mainly in the soma and not in the axons of RGCs.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Carmen Rodriguez-Cueto, Laura Garcia-Toscano, Irene Santos-Garcia, Marta Gomez-Almeria, Claudia Gonzalo-Consuegra, Francisco Espejo-Porras, Javier Fernandez-Ruiz, Eva de Lago
Summary: Cannabinoids have therapeutic effects by targeting different elements of the endocannabinoid system, with potential as neuroprotective agents in ALS. The focus is on the activation of the CB2 receptor to limit glial reactivity, and there is a need for clinical trials to confirm the potential of cannabinoid-based medicines in ALS.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Chuan Li, Luisa P. Mori, Shuang Lyu, Ronald Bronson, Adam J. Getzler, Matthew E. Pipkin, Susana T. Valente
Summary: The host factor p32 has been identified to interact with and stabilize Tat protein, promoting Tat-dependent HIV transcription. This finding suggests that p32 may be explored for HIV-targeted transcriptional inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Behavioral Sciences
Sonalika Bhalla, Sidharth Mehan, Andleeb Khan, Muneeb U. Rehman
Summary: Insulin-like growth factor-1 (IGF-1) and glucagon-like peptide-1 (GLP-1) play crucial roles in CNS development and protection. They prevent neuronal death and promote neuronal function through modulation of various cellular signaling pathways, making them potential therapeutic targets for neurodegenerative diseases.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Microbiology
Taizhen Liang, Qiao Zhang, Ziyao Wu, Pei Chen, Yifan Huang, Shuwen Liu, Lin Li
Summary: HIV-1 latency is influenced by host factors and viral proteins, with UHRF1 playing a crucial role in modulating Tat stability. By disrupting the Tat/cyclin T1/CDK9 complex, UHRF1 suppresses HIV-1 transcription and maintains latency. This study provides new insights into controlling Tat expression through host-pathogen interaction for modulating HIV-1 latency, suggesting potential therapeutic strategies for HIV-1 patients.
Article
Biochemistry & Molecular Biology
Hae-In Kim, Ga-Na Kim, Kyung-Lee Yu, Seong-Hyun Park, Ji Chang You
Summary: In this study, we developed two novel chimeric proteins, NHT and HTN, which specifically bind to HIV-1 viral RNA (vRNA) and effectively inhibit HIV-1 transcription and packaging, demonstrating new mechanisms of anti-HIV effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Rafael Franco, Alejandro Lillo, Rafael Rivas-Santisteban, Irene Reyes-Resina, Gemma Navarro
Summary: Neuronal survival relies on glial support, with activated microglia showing either harmful pro-inflammatory (M1) or beneficial neuroprotective (M2) phenotypes; maintaining the M1/M2 balance is crucial in neuroinflammation. Adenosine receptors play a significant role in increasing M2 cell numbers and preconditioning for better resilience against damaging events. The potential therapeutic targeting of adenosine receptors and adenosine-cannabinoid complexes for microglia-mediated neuroprotection is discussed.
Article
Biochemistry & Molecular Biology
Nabab Khan, Peter W. Halcrow, Zahra Afghah, Aparajita Baral, Jonathan D. Geiger, Xuesong Chen
Summary: The accumulation of HIV-1 Tat in endolysosomes may play an important role in controlling HIV-1 transactivation, further hindering the cure of HIV-1.
Review
Multidisciplinary Sciences
Alemu Gebrie
Summary: The melanocortin signaling system is composed of peptides, receptors, accessory proteins, and antagonists. It plays a role in various physiological and pathological conditions. There are five types of receptors that distribute in the central nervous system and peripheral tissues. The signaling pathways are complex and can lead to neuroprotection. Targeting components of this system may have therapeutic potentials.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Piotr Wojcik, Michal Biernacki, Natalia Domian, Neven Zarkovic, Elzbieta Skrzydlewska
Summary: This study evaluated the impact of Celecoxib on apoptosis in keratinocytes, and the results suggested that COX-2 inhibition can attenuate UVB-induced apoptosis, with AEA playing a significant role as an anti-apoptotic agent in this process.
Article
Pharmacology & Pharmacy
Rania Z. ElGamal, Mariane G. Tadros, Esther T. Menze
Summary: This study evaluates the neuroprotective effects of the DPP4 inhibitor linagliptin in a rotenone-induced rat model of Parkinson's disease. The results show that linagliptin can prevent motor deficits and tissue damage caused by rotenone through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Analytical
Zheng Ao, Hongwei Cai, Zhuhao Wu, Jonathan Krzesniak, Chunhui Tian, Yvonne Y. Lai, Ken Mackie, Feng Guo
Summary: The study introduces a human spinal organoid-on-a-chip device for modeling the biology and electrophysiology of human nociceptive neurons and dorsal horn interneurons. The device allows for testing nociceptive modulators and is cost-efficient, scalable, and easy to use. By integrating human sensory-spinal-cord organoids, the method shows promise for screening and validating novel therapeutics for human pain medicine discovery.
ANALYTICAL CHEMISTRY
(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
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)
Meeting Abstract
Biochemistry & Molecular Biology
Joshua L. Rein, Ken Mackie, Thomas R. Kleyman, Lisa M. Satlin
Article
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Summary: Traumatic brain injury is a risk factor for Alzheimer's disease and dementia. In this study, the researchers found that inhibiting monoacylglycerol lipase can reduce neuropathology caused by traumatic brain injury. The neuroprotective effects are mainly due to the inhibition of 2-arachidonoylglycerol metabolism in astrocytes, and not in neurons.
Article
Pharmacology & Pharmacy
Izaque de Sousa Maciel, Gabriel H. D. de Abreu, Claire T. Johnson, Rida Bonday, Heather B. Bradshaw, Ken Mackie, Hui-Chen Lu
Summary: The study using mice found that perinatal cannabinoid exposure affects behaviors in a sex-dependent manner, altering repetitive and hedonic behaviors. Additionally, perinatal exposure to THC or CBD prevents fluoxetine from enhancing coping behavior.
CANNABIS AND CANNABINOID RESEARCH
(2022)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.