Review
Biochemistry & Molecular Biology
Fariba Kokabi, Safieh Ebrahimi, Farshad Mirzavi, Nazanin Ghiasi Nooghabi, Seyedeh Fatemeh Hashemi, Seyed Isaac Hashemy
Summary: Diabetes is the world's fastest-growing disease characterized by persistent hyperglycemia and chronic complications. Substance P and its receptor system have been found to be involved in diabetes pathogenesis and can have both destructive and protective effects on the disease. Understanding the functional relevance of this system in diabetes may lead to new therapeutic options for diabetes and its associated chronic conditions.
Article
Neurosciences
Wenling Chen, James A. McRoberts, Helena S. Ennes, Juan Carlos Marvizon
Summary: The study showed that the cAMP signaling pathway mediates substance P release in the dorsal horn through the activation of PKA on NMDA receptors, with Epac2 signaling through Raf-mitogen activated protein kinase pathway to increase Ca2+ channel activity. The release of substance P induced by cAMP decreases during pain hypersensitivity.
Article
Virology
Shannon E. Ronca, Sarah M. Gunter, Rebecca Berry Kairis, Allison Lino, Jonathan Romero, Robia G. Pautler, Alan Nimmo, Kristy O. Murray
Summary: This study found a correlation between substance P and its receptor Neurokinin-1 in West Nile neuroinvasive disease. Blocking this interaction from disease onset modestly improved survival and prolonged time to death. The study has important implications for the development of new therapeutic options.
Article
Cell Biology
M. Brittany Johnson, Samantha R. Suptela, Sophie E. Sipprell, Ian Marriott
Summary: This study found that the interaction between neuropeptide substance P (SP) and its high affinity receptor neurokinin-1 receptor (NK-1R) enhances the inflammatory response of bone cells to Staphylococcus aureus infection. It also alters the production of pro- and anti-osteoclastogenic factors by bone cells, exacerbating inflammatory bone loss. The clinically approved NK-1R antagonist, aprepitant, was found to reduce local inflammation and pro-osteoclastogenic mediator expression in a mouse model of post-traumatic staphylococcal osteomyelitis.
Article
Biochemistry & Molecular Biology
Malihe Golestaneh, Mohsen Firoozrai, Hossein Javid, Seyed Isaac Hashemy
Summary: SW480 colorectal cancer cells exhibited significant metastatic activity following incubation with increasing doses of SP, as evidenced by increased MMP-2/MMP-9 enzyme activity, gene overexpression, and enhanced cell migration. Treatment with AP significantly reduced all SP-mediated metastatic effects (p-Value < 0.001).
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Orthopedics
Kyung Rae Ko, Soo-Hong Han, Sujin Choi, Hyun-Ju An, Eun-Bee Kwak, Yunhui Jeong, Minjung Baek, Jusung Lee, Junwon Choi, Il-Su Kim, Soonchul Lee
Summary: This study investigates the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo. The results showed that SPI improved tendon healing and restoration in the rat model.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2022)
Article
Medicine, General & Internal
Riffat Mehboob, Maher Kurdi, Ahmed Bamaga, Njoud Aldardeir, Hisham Nasief, Leena H. Moshref, Taghreed Alsinani, Almotasimbellah O. Rayes, Reem H. Jabbad
Summary: SARS-CoV-2 infection induces inflammation possibly through the release of Substance P in the trigeminal ganglion, which can be treated with neurokinin-1 receptor antagonists and glucocorticoids.
FRONTIERS IN MEDICINE
(2021)
Article
Critical Care Medicine
Jaclyn A. Smith, Amalie Harle, Rachel Dockry, Kimberley Holt, Philip Russell, Alex Molassiotis, Janelle Yorke, Ryan Robinson, Mark A. Birrell, Maria G. Belvisi, Fiona Blackhall
Summary: The study aimed to evaluate aprepitant in the treatment of cough in patients with lung cancer and investigate its mechanism on the vagal nerve tissue. The results showed that aprepitant significantly reduced cough frequency in lung cancer patients and improved patient-reported outcomes. Experimental findings indicated that aprepitant achieved its antitussive effect by inhibiting substance P-induced depolarization of the vagus nerve.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jae-Gyun Choi, Sheu-Ran Choi, Dong-Wook Kang, Jaehyuk Kim, Jin Bong Park, Hyun-Woo Kim
Summary: The study investigates the effects of ACE inhibitors on the expression of SP and the induction of mechanical allodynia in mice. The findings suggest that inhibition of ACE increases SP levels, contributing to mechanical allodynia.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Ophthalmology
Seok Jae Lee, Sang-Taek Im, Jun Wu, Chang Sik Cho, Dong Hyun Jo, Yihe Chen, Reza Dana, Jeong Hun Kim, Sang-Mok Lee
Summary: The study confirmed the role of the SP/NK1R system in lymphangiogenesis, and inhibition of NK1R using an antagonist or NK1R-targeted siRNA suppressed lymphangiogenesis and expression of VEGF receptor 3, leading to the inhibition of pathologic corneal lymphangiogenesis in DED mouse model.
Article
Neurosciences
Jacob C. A. Edvinsson, Philip Reducha, Majid Sheykhzade, Karin Warfvinge, Kristian A. Haanes, Lars Edvinsson
Summary: Substance P (SP) and calcitonin gene-related peptide (CGRP) have been potential drug candidates in migraine therapy, with CGRP receptor inhibition established as an effective treatment. However, clinical trials showed that inhibition of neurokinin receptor 1 (NK1R) did not alleviate acute migraine attacks. Experimental results suggest that SP and CGRP may work together to exacerbate painful stimuli in the trigeminovascular system.
Review
Behavioral Sciences
Sean J. O'Sullivan, James S. Schwaber
Summary: Alcohol and opioids, despite their distinct effects on mammalian systems, share commonalities in withdrawal syndromes, indicating potential similar addiction mechanisms. Neurovisceral feedback may generate antireward effects for both substances. Gut dysbiosis may contribute to alcohol and opioid withdrawal syndromes by stimulating peripheral and neuroinflammation pathways.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Critical Care Medicine
Adam Safwat, Adel Helmy, Arun Gupta
Summary: This review examines the role of substance P and its receptor neurokinin-1 in neuroinflammation following traumatic brain injury. It explores the evidence for neurokinin-1 receptor antagonism as a therapeutic approach to reduce deleterious effects and improve clinical outcomes. Substance P expression increases after traumatic brain injury and its binding to the neurokinin-1 receptor leads to neurogenic inflammation, causing increased intracranial pressure. Animal models have shown that neurokinin-1 receptor antagonism can reduce brain edema and intracranial pressure. This review summarizes the scientific and clinical rationale for substance P antagonism as a promising therapy for human TBI.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Biochemistry & Molecular Biology
Federica Benvenuti, Nazzareno Cannella, Serena Stopponi, Laura Soverchia, Massimo Ubaldi, Veronica Lunerti, Valentina Vozella, Bryan Cruz, Marisa Roberto, Roberto Ciccocioppo
Summary: Alcoholism is characterized by high alcohol intake and negative emotional state during abstinence. Stress, HPA axis dysregulation, and alterations in GR function are linked to the transition to alcohol use disorder. Pharmacological antagonism of GR selectively reduces alcohol intake, with differences in response seen between male and female rats and genetically selected strains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Shudan Wang, Lingjia Liu, Tomas Blanco, Hongyan Ge, Yutong Xia, Kunpeng Pang, Yihe Chen, Reza Dana
Summary: This study demonstrated that topical blockade of substance P can effectively prevent and treat allergy-related ocular redness by suppressing blood vessel dilation and allergic inflammation.
Article
Biochemistry & Molecular Biology
Andrea L. Johnstone, Nadja S. Andrade, Estelle Barbier, Bohdan B. Khomtchouk, Christopher A. Rienas, Kenneth Lowe, Derek J. Van Booven, Esi Domi, Rustam Esanov, Samara Vilca, Jenica D. Tapocik, Keli Rodriguez, Danielle Maryanski, Michael Christopher Keogh, Marcus W. Meinhardt, Wolfgang H. Sommer, Markus Heilig, Zane Zeier, Claes Wahlestedt
Summary: This study identified 11 dysregulated epigenetic enzymes in the brain of alcohol-dependent rats during protracted abstinence, with KDM6B showing region-specific dysregulation in the prefrontal cortex and nucleus accumbens. The upregulation of KDM6B in alcohol-dependent rats was associated with decreased trimethylation levels at histone H3, lysine 27, and enrichment of alcohol-induced changes in H3K27me3 at genes in the IL-6 signaling pathway, implicating a novel KDM6B-mediated epigenetic signaling pathway integrated with inflammatory pathways in the development of alcohol addiction.
Editorial Material
Clinical Neurology
Carolina L. Haass-Koffler, Jesse R. Schank
Review
Neurosciences
Jesse R. Schank
Article
Neurosciences
Christopher A. Guevara, Bridget A. Matikainen-Ankney, Nebojsa Kezunovic, Katherine LeClair, Alexander P. Conway, Caroline Menard, Meghan E. Flanigan, Madeline Pfau, Scott J. Russo, Deanna L. Benson, George W. Huntley
JOURNAL OF NEUROPHYSIOLOGY
(2020)
Article
Neurosciences
Meghan E. Flanigan, Hossein Aleyasin, Long Li, C. Joseph Burnett, Kenny L. Chan, Katherine B. LeClair, Elizabeth K. Lucas, Bridget Matikainen-Ankney, Romain Durand-de Cuttoli, Aki Takahashi, Caroline Menard, Madeline L. Pfau, Sam A. Golden, Sylvain Bouchard, Erin S. Calipari, Eric J. Nestler, Ralph J. DiLeone, Akihiro Yamanaka, George W. Huntley, Roger L. Clem, Scott J. Russo
NATURE NEUROSCIENCE
(2020)
Review
Neurosciences
Meghan E. Flanigan, Thomas L. Kash
Summary: The bed nucleus of the stria terminalis (BNST) has been implicated in neuropsychiatric disorders characterized by stress and drug-induced alterations in mood, arousal, motivation, and social behavior. However, its role in social behavior has been understudied, especially in terms of cell types and circuits. This review summarizes the existing literature, focusing on pharmacological and circuit-based behavioral studies in rodents.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Kristina K. Deonaraine, Qian Wang, Haoxiang Cheng, Kenny L. Chan, Hsiao-Yun Lin, Kalena Liu, Lyonna F. Parise, Flurin Cathomas, Katherine B. Leclair, Meghan E. Flanigan, Long Li, Hossein Aleyasin, Christopher Guevara, Ke Hao, Bin Zhang, Scott J. Russo, Jun Wang
JOURNAL OF NEUROSCIENCE RESEARCH
(2020)
Article
Neurosciences
Kazuhiko Yamamuro, Lucy K. Bicks, Michael B. Leventhal, Daisuke Kato, Susanna Im, Meghan E. Flanigan, Yury Garkun, Kevin J. Norman, Keaven Caro, Masato Sadahiro, Klas Kullander, Schahram Akbarian, Scott J. Russo, Hirofumi Morishita
NATURE NEUROSCIENCE
(2020)
Article
Behavioral Sciences
J. D. Tapocik, J. R. Schank, J. R. Mitchell, R. Damazdic, C. L. Mayo, D. Brady, A. B. Pincus, C. E. King, M. Heilig, G. I. Elmer
Summary: This study established a novel rodent model of adolescent stress and showed that exposure to predatory animals during adolescence results in significant adult behavioral and neurobiological disturbances. The findings suggest that adolescent stress can lead to adverse behavioral outcomes and neurobiological abnormalities in adulthood.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Retraction
Biology
Lara S. Hwa, Sofia Neira, Meghan E. Flanigan, Christina M. Stanhope, Melanie M. Pina, Dipanwita Pati, Olivia J. Hon, Waylin Yu, Emily Kokush, Rachel Calloway, Kristen Boyt, Thomas L. Kash
Article
Neurosciences
Kristen N. Amico, Miranda E. Arnold, Morgan S. Dourron, Matthew G. Solomon, Jesse R. Schank
Summary: This study found that female rats consumed more alcohol and oxycodone than males when given access to both drugs. The effect on alcohol intake persisted even when oxycodone was removed. Re-exposure to oxycodone cues and the administration of the stressor yohimbine drove reinstatement of oxycodone-seeking behavior in females, but not in males, possibly due to lower levels of oxycodone intake in male rats during active self-administration. Additionally, yohimbine increased alcohol consumption.
PSYCHOPHARMACOLOGY
(2022)
Article
Psychology, Biological
E. B. Decker Ramirez, M. E. Arnold, K. T. McConnell, M. G. Solomon, K. N. Amico, J. R. Schank
Summary: Recent research has shown that inflammatory pathways play a role in depressive-like behavior and excessive alcohol consumption. The study exposed male and female mice to LPS and found that it decreased social interaction in females but not in males. LPS also increased proinflammatory cytokine expression and escalated alcohol consumption in both sexes. Furthermore, administering a NK1R antagonist reduced escalated alcohol consumption in female mice treated with LPS.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Neurosciences
Meghan E. Flanigan, Carol Gianessi, Megan Castle, Winifred Dorlean, Tori Sides, Thomas L. Kash
Summary: The serotonin 5HT(2c) receptor plays an important role in alcohol-related behaviors, with differences between males and females. While gene knockdown of 5HT(2c) in BNST has no significant effect, chemogenetic inhibition of BNST 5HT(2c)-containing neurons increases operant alcohol self-administration behavior. BNST5HT2c neurons inhibit aversive responses to alcohol consumption through sex-dependent disinhibition of vlPAG neurons.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Matthew Solomon, Sadie Nennig, Kristen Amico, Miranda Arnold, Mallory Cotton, Kimberly Whiting, Hannah Fulenwider, Jesse Schank
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Substance Abuse
Soo K. Shin, Sydney E. Sneed, Sadie E. Nennig, Savannah R. Cheek, Holly A. Kinder, Matthew G. Solomon, Jesse R. Schank, Franklin D. West
Summary: Pigs are an attractive model for studying alcohol abuse disorder due to their comparable alcohol metabolism and consumption behavior. This study found that adolescent pigs voluntarily consumed alcohol to intoxication, displaying similar consumption and intoxication behavior to humans, making them a valuable tool for research on human patients.
ALCOHOL AND ALCOHOLISM
(2021)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)