Article
Biochemistry & Molecular Biology
Yuheng Shan, Yuying Cen, Yanjin Zhang, Ruishu Tan, Jiahua Zhao, Zhiyong Nie, Jiatang Zhang, Shengyuan Yu
Summary: The study demonstrated that P-glycoprotein inhibition can enhance the brain concentration of ceftriaxone (CFX) and increase its penetration across the blood-brain barrier (BBB). Cyclosporin A increased both the brain concentration and the ratio of unbound brain to unbound blood concentration of CFX in a dose-dependent manner, while verapamil only increased the brain concentration of CFX without affecting the penetration ratio across the BBB. Future studies with more selective P-gp inhibitors or knockout mouse models are needed to further investigate the impact of P-gp inhibition on CFX penetration across the BBB.
NEUROCHEMICAL RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Nazneen Pathan, Pravin Shende
Summary: P-Glycoprotein plays a vital role in the blood-brain barrier, protecting the central nervous system from infections and external toxic molecules. It is essential in various brain-related conditions but also poses a significant challenge in drug delivery across the blood-brain barrier.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Vinicius Cavicchioli Azevedo, Christopher J. Kennedy
Summary: This study investigated the neuroprotective effects of inducing the blood-brain barrier protein P-gp with CTZ in zebrafish against the neurotoxicant IVM. The results showed that P-gp induction may have limited protective effects on the zebrafish CNS from IVM. Additionally, the effects of IVM and P-gp induction were not influenced by feeding or fasting.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Zhiyu Jin, Yu Han, Danshen Zhang, Zhongqiu Li, Yongshuai Jing, Beibei Hu, Shiguo Sun
Summary: Depression is a growing mental disease in modern society, with low cure rates and high recurrence rates. The current treatment methods, primarily drug therapy combined with psychological and physical therapy, have limitations. Intranasal administration may provide a better option for the delivery of antidepressant medication.
Article
Geriatrics & Gerontology
Liangliang Huang, Yan Chen, Rui Liu, Binbin Li, Xuan Fei, Xiang Li, Ge Liu, Yunman Li, Baohui Xu, Weirong Fang
Summary: Increased expression of P-gp after ischemic injury leads to dysfunction and hyperpermeability of the BBB by suppressing Akt/mTOR-induced endothelial autophagy.
Article
Biochemistry & Molecular Biology
Vinicius C. Azevedo, Christopher J. Kennedy
Summary: This study examines the role of the blood-brain barrier ATP-binding cassette protein transporter P-glycoprotein (P-gp) in protecting zebrafish from the neurotoxic effects of the pesticide ivermectin. The results show that the presence of the competitive inhibitor cyclosporin A (CsA) increases the adverse effects of ivermectin on swimming and behavior in the fish. Additionally, fasting does not affect the protective role of P-gp against ivermectin. These findings suggest that P-gp plays a crucial role in defending fish from environmental neurotoxicants.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jae Pyun, Huijing Koay, Pranav Runwal, Celeste Mawal, Ashley I. Bush, Yijun Pan, Paul S. Donnelly, Jennifer L. Short, Joseph A. Nicolazzo
Summary: Cu(ATSM) enhances the expression and function of P-gp at the blood-brain barrier, which has important implications for CNS drug delivery and clearance of A beta in AD.
Article
Plant Sciences
Li Zhang, Liwen Wang, Li Huang, Yanni Zhao, Hongling Ding, Binglong Li, Lingmiao Wen, Wei Xiong, Yanjun Liu, Tinglan Zhang, Liudai Zhang, Lanlan Wu, Qing Xu, Yuqing Fan, Guihua Wei, Qiaozhi Yin, Yunhui Chen, Tiane Zhang, Zhiyong Yan
Summary: Valeriana jatamansi extract may modulate intestinal flora, induce the expression of ZO-1 and occludin, protect the blood-brain barrier, and exert an antidepressant effect.
PHARMACEUTICAL BIOLOGY
(2021)
Article
Toxicology
Laurens F. M. Verscheijden, Jan B. Koenderink, Saskia N. de Wildt, Frans G. M. Russel
Summary: The study found that BBB Pgp activity is species-specific, and an age-dependent PBPK model can optimize predictions of brain drug concentrations. The methods used in the study have the potential to address challenges in extrapolating brain drug disposition and toxicity.
ARCHIVES OF TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Amanda B. Chai, Richard Callaghan, Ingrid C. Gelissen
Summary: This review summarizes the current understanding of P-gp regulation in the brain, including transcriptional, post-transcriptional, and post-translational mechanisms, aiming to provide new strategies for optimizing therapeutic outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Ryuta Jomura, Shin-ichi Akanuma, Bjorn Bauer, Yukiko Yoshida, Yoshiyuki Kubo, Ken-ichi Hosoya
Summary: The study investigated the transport of phenytoin across the blood-brain barrier (BBB), identifying that MCT8 participates in the efflux of phenytoin from the brain to the blood. Meanwhile, P-gp did not affect the efflux of phenytoin from the brain.
PHARMACEUTICAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Jessica L. Antunes, Joana Amado, Francisco Veiga, Ana Claudia Paiva-Santos, Patricia C. Pires
Summary: Depression and anxiety are common and debilitating psychiatric disorders, often treated with antidepressants or anxiolytics. However, oral administration is limited by the blood-brain barrier, reducing drug effectiveness. To overcome this, strategies such as intranasal administration, nanosystems, and drug functionalization have been used to enhance brain drug targeting. In vivo studies have shown promising results, suggesting that these strategies could lead to improved therapies for depression and anxiety disorders.
Article
Veterinary Sciences
Andrea Fischer, Velia-Isabel Huelsmeyer, Viviana P. Munoz P. Schmieder, Andrea Tipold, Marion Kornberg, Florian Koenig, Felix K. Gesell, Liza K. Ahrend, Holger A. Volk, Heidrun Potschka
Summary: The efficacy and tolerability of COX-2 inhibitor add-on therapy in dogs with phenobarbital-resistant epilepsy were investigated in this study. Results showed that only a small number of dogs responded to the treatment, indicating that overall, this combination therapy is not significantly effective in overcoming epilepsy resistant to phenobarbital.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Cell Biology
Chunfu Li, Yongzhi Wang, Huiting Liu, Xinghua Zhang, Dalai Baolige, Shihua Zhao, Wei Hu, Yang Yang
Summary: Lab-attenuated rabies virus (RABV) is a less pathogenic variant compared to wild-type RABV, and through serial passage in mice brains, a safe and well-replicating strain was developed with specific amino acid substitutions on the G protein. This decreased pathogenicity was linked to increased RABV-G expression, higher apoptosis levels in infected cells, and effects on DCs and blood-brain barrier permeability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Francisco Donoso, John F. Cryan, Loreto Olavarria-Ramirez, Yvonne M. Nolan, Gerard Clarke
Summary: Depression is a major public health concern, and current pharmacological treatments are not equally effective for all patients. Lifestyle-oriented approaches, such as physical exercise and special diets, show promise as adjunctive therapies. However, the mechanisms underlying these strategies are not fully understood. Accumulating evidence suggests that physical exercise and specific diets can modulate the immune system and gut microbiota composition.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Kirsten Berding, Thomaz F. S. Bastiaanssen, Gerard M. Moloney, Serena Boscaini, Conall R. Strain, Andrea Anesi, Caitriona Long-Smith, Fulvio Mattivi, Catherine Stanton, Gerard Clarke, Timothy G. Dinan, John F. Cryan
Summary: This study investigated the impact of a psychobiotic diet on the microbial profile and mental health in a healthy population. The results showed that the psychobiotic diet reduced perceived stress and improved stress levels, although it only had subtle effects on microbial composition and function. In addition, higher adherence to the diet was associated with greater decreases in perceived stress.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Harriet Schellekens, Gabriela Ribeiro, Cristina Cuesta-Marti, John F. Cryan
Summary: Emerging evidence suggests that the microbiome plays a crucial role in mediating the effects of nutrition on the gut-brain axis. However, it is still unclear whether nutrition directly affects the microbiota-gut-brain interaction or if diet influences the composition and function of the microbiota, which in turn affects central nervous system function, brain phenotypes, and behavior. More research is needed to understand the mechanisms and translate the findings from animal and in vitro studies to human intervention studies.
NUTRITIONAL NEUROSCIENCE
(2023)
Article
Health Care Sciences & Services
Anna Ratsika, Joana S. Cruz Pereira, Caoimhe M. K. Lynch, Gerard Clarke, John F. Cryan
Summary: There is growing recognition of the gut microbiota's key role in maintaining homeostasis and influencing brain and behavior. Communication between the gut and the brain, mediated by the immune system, appears to be crucial in understanding various neuropsychiatric disorders. This review discusses the factors contributing to the balance between health and disease of these systems and explores the potential mechanistic implications of gut microbiota modulation on host brain and behavior across the lifespan.
Article
Neurosciences
Emily G. Knox, Caoimhe M. K. Lynch, Ye Seul Lee, Caitriona M. O'Driscoll, Gerard Clarke, John F. Cryan, Maria R. Aburto
Summary: The gut microbiota communicates with the brain through various pathways, including the blood-cerebrospinal fluid barrier. Using a germ-free mouse model, researchers found that the integrity of the blood-cerebrospinal fluid barrier in the choroid plexus epithelium was compromised. However, there were no differences observed in the capillary structure.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Paraminder Dhillon, John F. Cryan
Summary: John F. Cryan is a leading researcher in the field of microbiome and neuroscience. He has made significant contributions to understanding the impact of gut microbiota on brain development and behavior, particularly in the context of depression. His research has been recognized with numerous awards and he has published over 600 peer-reviewed papers.
Article
Gastroenterology & Hepatology
Beatriz Lobo, Monica Tramullas, Beate-C Finger, Kevin W. Lomasney, Caroll Beltran, Gerard Clarke, Javier Santos, Niall P. Hyland, Timothy G. Dinan, John F. Cryan
Summary: This study investigated the effects of chronic unpredictable psychological stress on intestinal motility and enteric function. The results showed that chronic stress led to increased food intake, weight gain, reduced stool output, and delayed gastrointestinal transit. Moreover, stress also decreased neural plasticity and monoamine levels in the intestine. These findings highlight the relationship between psychological stress and gut health.
JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Review
Psychiatry
Nuala Murray, Sukainah Al Khalaf, Thomaz F. S. Bastiaanssen, David Kaulmann, Edgar Lonergan, John F. Cryan, Gerard Clarke, Ali S. Khashan, Karen O'Connor
Summary: A systematic review and meta-analysis revealed alterations in the composition and function of the gut microbiota in patients with psychosis or schizophrenia. While no significant differences were found in diversity, there were increases in specific microbial taxa and associations with brain structure changes. These findings suggest a potential role for the microbiome in the etiology and symptomatology of schizophrenia.
SCHIZOPHRENIA BULLETIN
(2023)
Review
Clinical Neurology
David M. Raizen, Janet Mullington, Christelle Anaclet, Gerard Clarke, Hugo Critchley, Robert Dantzer, Ronald Davis, Kelly L. Drew, Josh Fessel, Patrick M. Fuller, Erin M. Gibson, Mary Harrington, W. Ian Lipkin, Elizabeth B. Klerman, Nancy Klimas, Anthony L. Komaroff, Walter Koroshetz, Lauren Krupp, Anna Kuppuswamy, Julie Lasselin, Laura D. Lewis, Pierre J. Magistretti, Heidi Y. Matos, Christine Miaskowski, Andrew H. Miller, Avindra Nath, Maiken Nedergaard, Mark R. Opp, Marylyn D. Ritchie, Dragana Rogulja, Asya Rolls, John D. Salamone, Clifford Saper, Vicky Whittemore, Glenn Wylie, Jarred Younger, Phyllis C. Zee, H. Craig Heller
Summary: The workshop "Beyond the Symptom: The Biology of Fatigue" was a virtual event held on September 27-28, 2021. It aimed to bring together clinicians and scientists using different research approaches to understand fatigue in various conditions and identify gaps in our understanding of its biology. This workshop summary highlights key issues discussed and provides a list of promising future research directions, without aiming to comprehensively review the state of understanding or reprise all the presentations.
Article
Food Science & Technology
Serena Boscaini, Peter Skuse, Kanishka N. Nilaweera, John F. Cryan, Paul D. Cotter
Summary: This review provides an overview of the beneficial effects of whey protein (WP) and its components on human health, particularly in controlling obesity and its comorbidities. WP consumption positively impacts energy balance and obesity-related parameters, primarily through modulation in adipose tissue metabolism and changes that occur in the gastrointestinal tract. Furthermore, WP also has a positive impact on gut microbiota, mood, and behavior. This review emphasizes the importance of WP supplementation in preventing or treating obesity and highlights areas for further research.
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2023)
Article
Psychiatry
Xuemei Li, Teng Teng, Wei Yan, Li Fan, Xueer Liu, Gerard Clarke, Dan Zhu, Yuanliang Jiang, Yajie Xiang, Ying Yu, Yuqing Zhang, Bangmin Yin, Lin Lu, Xinyu Zhou, Peng Xie
Summary: This study induced depressive-like behaviors in rats using four stress models and investigated molecular changes in the hippocampus using proteomic and metabolomic techniques. A schematic model of AKT and MAPK signaling pathways network and their interactions was presented, and cascade reactions were revealed. Western blot confirmed changes in p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB in at least one depression model, with p-AKT, p-ERK12, p-MEK1, and p-P38 identified as common alterations in all four models. This research sheds light on the pathogenesis of depression and may contribute to the development of more effective treatment strategies.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Psychiatry
Mary I. I. Butler, Thomaz F. S. Bastiaanssen, Caitriona Long-Smith, Sabrina Morkl, Kirsten Berding, Nathaniel L. L. Ritz, Conall Strain, Dhrati Patangia, Shriram Patel, Catherine Stanton, Siobhain M. M. O'Mahony, John F. F. Cryan, Gerard Clarke, Timothy G. G. Dinan
Summary: The gut microbiome differs in composition and function between patients with social anxiety disorder (SAD) and healthy controls. This study found elevated levels of Anaeromassillibacillus and Gordonibacter genera in SAD patients, while Parasuterella genus was enriched in healthy controls. At a species level, Anaeromassillibacillus sp An250 was more abundant in SAD patients, while Parasutterella excrementihominis was higher in controls. The study suggests the importance of larger, longitudinal studies to confirm these findings and explore the potential clinical implications of these microbiome changes in SAD.
TRANSLATIONAL PSYCHIATRY
(2023)
Review
Nutrition & Dietetics
Hajara Aslam, Mojtaba Lotfaliany, Daniel So, Kirsten Berding, Michael Berk, Tetyana Rocks, Meghan Hockey, Felice N. Jacka, Wolfgang Marx, John F. Cryan, Heidi M. Staudacher
Summary: This study conducted a systematic literature review and meta-analysis to explore the effects of dietary fibers on depressive and anxiety outcomes. The results showed a negative correlation between fiber intake and depressive and anxiety outcomes in observational studies. However, current randomized controlled trials did not support the use of fiber supplementation for improving depressive or anxiety outcomes. Further research, including clinical trials in specific populations and using a wider range of fiber types, is needed.
Correction
Neurosciences
H. Schellekens, G. Ribeiro, C. Cuesta-Marti, J. F. Cryan
NUTRITIONAL NEUROSCIENCE
(2023)