Article
Neurosciences
Yasmine Belaidouni, Diabe Diabira, Jinwei Zhang, Jean-Charles Graziano, Francesca Bader, Aurelie Montheil, Clement Menuet, Gary A. Wayman, Jean-Luc Gaiarsa
Summary: The study found that in late symptomatic stages, there was no difference in the relative amount of KCC2 and NKCC1 in the hippocampus of Mecp2-null mice, but there was over-phosphorylation. There were also no differences in the inhibitory strength and reversal potential of GABA(A)-receptor-mediated responses in Mecp2-null CA3 pyramidal neurons compared to wild-type at any stages studied. These data indicate the presence of a functional chloride extrusion mechanism in Mecp2-null CA3 pyramidal neurons at symptomatic stages.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Anatomy & Morphology
Mikhail Yu Stepanichev, Tatyana Goryakina, Anna Manolova, Natalia Lazareva, Alexey Kvichanskii, Liya Tretyakova, Maria Volobueva, Natalia Gulyaeva
Summary: Neonatal proinflammatory challenge may contribute to psychiatric disorders in adults by affecting neuroplasticity and cognition. The effects of NPC on the composition of hippocampal GABAergic neuronal population suggest a role in maintaining excitation/inhibition homeostatic balance.
BRAIN STRUCTURE & FUNCTION
(2021)
Review
Biochemistry & Molecular Biology
Felipe V. Gomes, Anthony A. Grace
Summary: Although currently available antipsychotic drugs can reduce psychotic symptoms in schizophrenia patients, they have numerous side effects and are not effective against negative and cognitive symptoms. Developing new drugs that target the excitatory/inhibitory balance in the brain may offer a more effective approach in treating schizophrenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Celine Caravagna, Alexis Casciato, Jacques-Olivier Coq, Sylvie Liabeuf, Cecile Brocard, Julie Peyronnet, Laurence Bodineau, Florence Cayetanot
Summary: Prenatal hypoxia disrupts the development of Cl- cotransporters KCC2 and NKCC1, leading to alterations in central respiratory drive. This disruption may have long-term effects on the functioning of GABA(A) and glycinergic systems.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eligija Damanskiene, Ingrida Balnyte, Angelija Valanciute, Marta Maria Alonso, Aidanas Preiksaitis, Donatas Stakisaitis
Summary: The study found that a 100 mu g dose of TMZ reduced invasion and blood vessels in PBT24 xenografts, with no impact on SF8628 tumors. TMZ had a significant effect on PCNA expression in both PBT24 and SF8628 tumors, but did not alter EZH2 expression. A 50 mu M dose of TMZ significantly increased RNA expression of the NKCC1 gene in both cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mark Stewart, Timothy Morello, Richard Kollmar, Rena Orman
Summary: With the increasing average human lifespan, the impact of neurodegenerative diseases on individuals and communities has grown, leading to the exploration of animal models such as the long-lived Seba's short-tailed fruit bat, Carollia perspicillata, for research on brain aging and neurodegeneration. This bat species shows anatomical similarities to primate and human hippocampal formation, offering unique advantages for studying these conditions through captive colony studies.
Review
Geriatrics & Gerontology
Pavel A. Kipnis, Shilpa D. Kadam
Summary: Epilepsy is a complex disorder associated with various neurological conditions, causing ongoing seizures for millions of patients worldwide despite optimal treatment. Refractory epilepsy poses a challenge for effective management, especially in cases of early-life seizures like those caused by perinatal hypoxic ischemic encephalopathy.
Article
Biochemistry & Molecular Biology
Sahel Motaghi, Hadi Moghaddam Dizaj Herik, Gholamreza Sepehri, Mehdi Abbasnejad, Saeed Esmaeli-Mahani
Summary: The study found that Salicylic acid has anxiolytic and hypnotic effects in animal models, partially exerting its anxiolytic effect through up-regulating GAD1 gene expression in the ventral part of the hippocampus.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Eligija Damanskiene, Ingrida Balnyte, Angelija Valanciute, Marta Marija Alonso, Donatas Stakisaitis
Summary: This study investigated the effects of valproic acid on the expression of co-transporter genes in pediatric glioblastoma cells, and found differences in response between male and female cells, suggesting gender-related differences in tumor cell biology.
Article
Biochemistry & Molecular Biology
Patricia Lam, Chitra Vinnakota, Beatriz Calvo-Flores Guzman, Julia Newland, Katie Peppercorn, Warren P. Tate, Henry J. Waldvogel, Richard L. M. Faull, Andrea Kwakowsky
Summary: Alzheimer's disease is a neurodegenerative disorder that requires the development of disease-modifying treatments. Recent evidence suggests that the GABA neurotransmitter system undergoes remodeling in AD, disrupting the excitatory/inhibitory balance in the brain. This study explores the expression levels of KCC2 and NKCC1 in AD and finds that chronic exposure to beta-amyloid alters the balance of KCC2 and NKCC1 expression in mouse hippocampal tissue. Furthermore, the study reveals that the drug bumetanide, used for AD therapy, is highly neurotoxic.
Article
Clinical Neurology
Che-Wen Tsai, Shih-Jen Tsai, Yi-Ju Pan, Hsin-Mei Lin, Tsung-Yu Pan, Feng-Yi Yang
Summary: This study aimed to investigate the restorative role of transcranial ultrasound stimulation (TUS) in counteracting cognitive deficits and GABAergic interneuron dysfunction in a simulation of schizophrenia. The results showed that low-intensity pulsed ultrasound (LIPUS) treatment improved cognitive deficits and ameliorated neuropathology in MK-801-treated rats.
Article
Environmental Sciences
Mengxi Lu, Xia He, Zhexiao Jiao, Zewen Hu, Zijing Guo, Shiyun Dai, Hui Wang, Dan Xu
Summary: Prenatal caffeine exposure can induce hypersensitivity of the hypothalamic-pituitary-adrenal axis in offspring rats, and hippocampal dysfunction might be involved in this process.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Juergen Graf, Chuanqiang Zhang, Stephan Lawrence Marguet, Tanja Herrmann, Tom Flossmann, Robin Hinsch, Vahid Rahmati, Madlen Guenther, Christiane Frahm, Anja Urbach, Ricardo Melo Neves, Otto W. Witte, Stefan J. Kiebel, Dirk Isbrandt, Christian A. Huebner, Knut Holthoff, Knut Kirmse
Summary: NKCC1 is the primary transporter for chloride uptake in immature principal neurons, and its function in vivo network dynamics and cognitive abilities remains unclear. The study found that deletion of NKCC1 from telencephalic glutamatergic neurons impacts neuronal synchrony in neonatal hippocampal brain slices, but has minor effects on network activity and behavioral performance in the long term.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Hoorie Mohaghghegh, Esmaeil Shahsavand Ananloo, Mahmoudreza Hadjighasem, Morteza Karimipour, Shiva Hashemizadeh, Seyyed Ali Ahmadi Abhari
Summary: This study investigated the expression levels of NKCC1 and KCC2 genes in the peripheral blood of patients with schizophrenia and their association with symptom scores. The results showed that the NKCC1 to KCC2 mRNA ratio was significantly increased in the total sample of cases and higher in male patients compared to male controls. There was also a trend towards a significant effect in female patients. The mRNA levels of NKCC1 and KCC2 genes and the NKCC1/KCC2 mRNA ratio were significantly associated with symptom scores.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Review
Neurosciences
Werner Kilb
Summary: This article discusses the effect of GABA on neuronal excitability, the complex spatiotemporal interaction between GABAergic and glutamatergic inputs, and mechanisms influencing [Cl-](i) beyond Cl- transporters expression. Research suggests that during early developmental stages, GABA can act as an inhibitory neurotransmitter.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Immunology
Ruben Garcia-Cabrerizo, Thaisa Barros-Santos, David Campos, John F. Cryan
Summary: The gut microbiota plays a crucial role in maintaining physiological balance and immunity, and is associated with addiction. Animal studies have shown a link between reward and social processes, which can be influenced by the gut microbiota, impacting neurodevelopment and social behaviors across different species. Depletion of the gut microbiota alters reward responses to drug and social stimuli, with a decrease in drug reward and an increase in social reward. Additionally, depleting the gut microbiota in the presence of positive social stimuli attenuates cocaine reward. These findings suggest that targeting the microbiota and enhancing social behavior could be beneficial in reducing harm from drug use.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Editorial Material
Immunology
Thaisa Barros-Santos, Gerard Clarke
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Immunology
Caoimhe M. K. Lynch, Caitlin S. M. Cowan, Thomaz F. S. Bastiaanssen, Gerard M. Moloney, Nigel Theune, Marcel van de Wouw, Eva Florensa Zanuy, Ana Paula Ventura-Silva, Martin G. Codagnone, Francisca Villalobos-Manriquez, Matilde Segalla, Fatma Koc, Catherine Stanton, Paul Ross, Timothy G. Dinan, Gerard Clarke, John F. Cryan
Summary: Numerous studies have shown that the gut microbiota plays a crucial role in neurodevelopment and behavior. Early-life exposure to antibiotics has been associated with increased risk of immune and metabolic diseases. Targeted antibiotic-induced disruption of the microbiota during critical developmental periods has enduring effects on physiology and behavior. This study demonstrates that microbiota disruption during early life alters the structure and function of the caecal microbiome, as well as immune cells and neurophysiology in adolescence. However, the effects on behavior are limited and subtle, suggesting the importance of the gut microbiota during critical windows of development.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
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)
Article
Medicine, General & Internal
Carina Carbia, Thomaz F. S. Bastiaanssen, Luigi Francesco Iannone, Ruben Garcia-Cabrerizo, Serena Boscaini, Kirsten Berding, Conall R. Strain, Gerard Clarke, Catherine Stanton, Timothy G. Dinan, John F. Cryan
Summary: This study investigated the effects of alcohol consumption on the gut microbiome and its association with social cognition, impulsivity, and craving. The results showed that binge drinking was associated with changes in the microbiome and difficulties in emotional recognition. Craving was strongly linked to alterations in the microbiome over time. These findings highlight the role of the gut microbiome as a regulator of social cognition and its relevance for addressing early alcohol-related issues during adolescence.
Article
Pharmacology & Pharmacy
Monique C. P. Mendonca, Yao Sun, Michael F. Cronin, Andrew J. Lindsay, John F. Cryan, Caitriona M. O'Driscoll
Summary: Huntington's disease (HD) is a neurodegenerative disease caused by a genetic mutation, and effective treatment options are still lacking. In this study, cyclodextrin-based nanoparticles (CDs) were used as a delivery system for antisense oligonucleotides (ASOs) to target the mutant huntingtin (mHTT) protein. Modified gamma-CDs showed the highest efficiency in delivering ASOs and successfully downregulated the levels of mHTT protein. Incorporating a brain-targeting peptide into the modified gamma-CDs further improved the downregulation effect. This study demonstrates the feasibility of using CDs as a platform for delivering ASO-based therapeutics for the treatment of HD.
Review
Ecology
Rie Matsuzaki, Eoin Gunnigle, Violette Geissen, Gerard Clarke, Jatin Nagpal, John F. Cryan
Summary: The gut microbiota, influenced by various factors including exposure to pesticides, plays a crucial role in maintaining host health, particularly influencing the brain and behavior. Studies on animals have shown that pesticides can negatively impact the gut microbiota, physiology, and health, leading to behavioral impairments. This review aims to assess whether changes in gut microbiota composition and function induced by pesticides are responsible for these behavioral alterations. However, the diversity in pesticide types, exposure doses, and experimental designs hinders direct comparisons between studies, and the mechanistic connection between the gut microbiota and behavioral changes remains insufficiently explored.
Article
Biochemistry & Molecular Biology
James M. Collins, Niall P. Hyland, Gerard Clarke, Patrick Fitzgerald, Marcela Julio-Pieper, David C. Bulmer, Timothy G. Dinan, John F. Cryan, Siobhain M. O'Mahony
Summary: The beta 3-AR agonist CL-316243 has been shown to reduce visceral hypersensitivity induced by early-life stress. It achieves this by altering tryptophan levels, affecting neuronal activation, and modulating colonic secretomotor activity.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Endocrinology & Metabolism
Cristina Cuesta-Marti, Friederike Uhlig, Begona Muguerza, Niall Hyland, Gerard Clarke, Harriet Schellekens
Summary: Oxytocin is closely related to gut microbiota and plays an important role in appetite regulation and social behavior.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Jodi L. Pawluski, Pauline Murail, Florine Grudet, Lena Bys, Anna V. Golubeva, Thomaz Bastiaanssen, Tim F. Oberlander, John F. Cryan, Siobhain M. O'Mahony, Thierry D. Charlier
Summary: This study aimed to determine how peripartum SSRI treatment may prevent the effects of gestational stress on plasticity in the maternal hippocampus, plasticity in the neonatal brain, and related changes in gut microbiota. The findings show significant changes to the maternal microbiome-gut-brain axis that may mediate plasticity in the maternal hippocampus. Additionally, gestational stress has a significant impact on neonatal gut microbiota and brain microglia density, while the effects of SSRIs are limited. This is the first study to explore the impact of gestational stress and SSRIs on the microbiome-gut-brain axis in the mother and neonate.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Psychology, Clinical
John R. Kelly, Gerard Clarke, Andrew Harkin, Sinead C. Corr, Stephen Galvin, Vishnu Pradeep, John F. Cryan, Veronica O'Keane, Timothy G. Dinan
Summary: Moving towards a systems psychiatry paradigm involves a comprehensive approach that considers complex interactions at different levels and takes into account external biofeedback signals. The gut microbiome, through the gut-brain axis, plays a critical role in unconscious parallel processing systems. The microbiota-gut-brain axis may have a role in different phases of psychedelic therapy.
INTERNATIONAL JOURNAL OF CLINICAL AND HEALTH PSYCHOLOGY
(2023)
Review
Neurosciences
Sarah-Jane Leigh, Friederike Uhlig, Lars Wilmes, Paula Sanchez-Diaz, Cassandra E. Gheorghe, Michael S. Goodson, Nancy Kelley-Loughnane, Niall P. Hyland, John F. Cryan, Gerard Clarke
Summary: The physiological consequences of stress often affect the gastrointestinal tract, and understanding the mechanisms behind these effects is important in the fields of neurogastroenterology and psychiatry. Stress-induced changes in the gut can increase susceptibility to gastrointestinal disorders and impair gut-brain communication. The gut microbiota is also sensitive to the effects of stress. This review focuses on different aspects of the gastrointestinal tract, including gut barrier function and gut-brain communication, and discusses the evidence for a role of stress in gastrointestinal disorders.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
