Article
Immunology
Lourdes Fernandez de Cossio, Chloe Lacabanne, Maude Bordeleau, Garance Castino, Phillip Kyriakakis, Marie-Eve Tremblay
Summary: Inflammation during pregnancy can impact brain development and result in disorders in offspring. Microglia play a critical role in this process, and alterations in their function may affect cognition and neurodevelopment.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Review
Psychiatry
Zahra Choudhury, Belinda Lennox
Summary: Schizophrenia is a complex neurodevelopmental disorder affecting a large number of people worldwide. The etiology involves genetic and environmental factors, with maternal immune activation during pregnancy implicated in increasing risk. Animal models and genome wide association studies have provided insights into the mechanisms, but research is still ongoing.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Tertia D. Purves-Tyson, Ulrike Weber-Stadlbauer, Juliet Richetto, Debora A. Rothmond, Marie A. Labouesse, Marcello Polesel, Kate Robinson, Cynthia Shannon Weickert, Urs Meyer
Summary: The research indicates that immune-related changes in the dopaminergic areas of the midbrain of schizophrenia patients are associated with a subgroup showing high immune status. The study also suggests that maternal immune activation (MIA) may be one of the contributing factors underlying persistent neuroimmune changes in the midbrain of people with schizophrenia.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Shivaprasad H. Sathyanarayana, Jasmine A. Saunders, Jacob Slaughter, Kamran Tariq, Rajarshi Chakrabarti, Madhumala K. Sadanandappa, Bryan W. Luikart, Giovanni Bosco
Summary: This study investigated the interaction between PTEN and FMRP in the development of hippocampal granule neurons. The findings suggest that PTEN protein expression is negatively regulated by FMRP, and disruptions in this regulation may contribute to the pathogenesis of Fmr1-related fragile X neurodevelopmental disorders. The study also showed that heterozygosity of Pten can partially restore cellular phenotypes caused by Fmr1 knockout, while complete deletion of both Pten and Fmr1 results in severe abnormalities in neuron development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Stephanie Raymann, Sina M. Schalbetter, Ron Schaer, Alexandra C. Bernhardt, Flavia S. Mueller, Urs Meyer, Ulrike Weber-Stadlbauer
Summary: Prenatal immune activation can have transgenerational effects on brain and behavior, affecting cognitive functions and gene expression patterns across multiple generations. These effects are found to be transmitted through both maternal and paternal lineages and are accompanied by changes in maternal care behavior.
Article
Developmental Biology
Gopalan Gnanaguru, Steven J. Tabor, Gracia M. Bonilla, Ruslan Sadreyev, Kentaro Yuda, Jorg Kohl, Kip M. Connor
Summary: Microglia play a crucial role in neurovascular development, specifically in regulating the spatial patterning of astrocytes and promoting the formation of superficial blood vessels in the neuroretina. This study demonstrates that microglia achieve this through the complement C3/C3aR axis, which regulates the formation of the spatially organized astrocyte template necessary for subsequent vascular growth. Lack of C3 or C3aR leads to increased astrocyte density and elevated vascular density due to abnormal extracellular matrix gene expression.
Article
Cell Biology
Kitti Rusznak, Adam Istvan Horvath, Kinga Pohli-Toth, Anett Futacsi, Agnes Kemeny, Gabriella Kiss, Zsuzsanna Helyes, Boldizsar Czeh
Summary: Acute and chronic arthritis can affect adult hippocampal neurogenesis through a cascade of molecular and cellular changes, resulting in a decrease in the number of doublecortin-positive cells and an increase in the density of CD68-positive macrophages/microglia.
Review
Immunology
Frauke Zipp, Stefan Bittner, Dorothy P. Schafer
Summary: Cytokines play a crucial role in immune cell communication and regulate various physiological processes, including immune and inflammatory responses. Recent studies have shown that these cytokines also impact neuronal structure and function, from fine-tuning neurotransmission to regulating synapse number and influencing global neuronal networks and behavior. These findings highlight the significance of immune system cytokines in regulating synapse and neural network structure and function.
Article
Biochemistry & Molecular Biology
Rebecca M. Woods, Jarred M. Lorusso, Isabella Harris, Hager M. Kowash, Christopher Murgatroyd, Joanna C. Neill, Jocelyn D. Glazier, Michael Harte, Reinmar Hager
Summary: Exposure to maternal immune activation (MIA) in utero increases the risk of neurodevelopmental disorders. The study investigates the relationship between MIA and cognitive deficits by focusing on Reelin signalling in the brain. The findings suggest that dysregulation of Reelin signalling due to MIA contributes to cognitive deficits through altered NMDA receptor function.
Article
Cell Biology
Kelsey D. McDermott, M. Agustina Frechou, Jake T. Jordan, Sunaina S. Martin, J. Tiago Goncalves
Summary: Aging is associated with cognitive deficits, especially in spatial memory. The hippocampal dentate gyrus (DG) is important for processing spatial information but is vulnerable to aging. Using two-photon calcium imaging, researchers found that neuronal activity and spatial representations in the DG were impaired in aged mice. However, with repeated exposure to the same environment, spatial tuning and information levels in aged mice improved, while activity remained elevated.
Article
Immunology
Dimitrios Andreou, Kjetil Nordbo Jorgensen, Stener Nerland, Kristine Engen, Robert H. Yolken, Ole A. Andreassen, Ingrid Agartz
Summary: CMV infection is associated with smaller dentate gyrus volume in male patients with severe mental illness, but not in healthy controls or female patients. Vulnerability to CMV infection in men with SMI is suggested by the results.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Neurosciences
Robert E. Featherstone, Takeshi Shimada, Lindsey M. Crown, Olya Melnychenko, Janice Yi, Mitsuyuki Matsumoto, Katsunori Tajinda, Takuma Mihara, Megumi Adachi, Steven J. Siegel
Summary: In this study, the behavioral phenotypes and neurophysiological profile of CaMKII alpha-hKO mice were characterized. These mice displayed hypoactivity, less anxiety-like behavior, and severe cognitive dysfunction. EEG recording revealed altered event-related potentials and increased power in theta range time-frequency measures. The findings suggest that CaMKII alpha-hKO mice may model a subpopulation of schizophrenia patients.
Article
Psychiatry
Amit Kumar Madeshiya, Carl Whitehead, Ashutosh Tripathi, Anilkumar Pillai
Summary: Using the learned helplessness model of depression, researchers investigated the role of C1q, the initiator of classical complement pathway, in mediating stress-induced depressive-like behavior in mice. They found that C1q deletion exacerbated the learned helplessness behavior and was associated with significant reductions in C1q mRNA levels in the prefrontal cortex.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Yeonggwang Hwang, Hyoung-Chun Kim, Eun-Joo Shin
Summary: In this study, it was found that repeated BKM120 treatment induced anxiety- and depression-like behaviors in mice and these behaviors were positively correlated with the extent of DCX-positive cell migration. The treatment also affected the activity of Akt, JNK, DCX, and RhoA.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Anesthesiology
Qian Zhai, Ying Zhang, Mao Ye, Shan Zhu, Jianyu Sun, Yue Wang, Bin Deng, Daqing Ma, Qiang Wang
Summary: This study found that sleep deprivation leads to cognitive decline, associated with synapse elimination and complement pathway activation, and dexmedetomidine can protect against these effects. These findings provide a basis for further research on the role of dexmedetomidine in preventing cognitive deficits caused by sleep deprivation.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Biology
Marcus Augusto-Oliveira, Gabriela P. Arrifano, Charlotte Isabelle Delage, Marie-Eve Tremblay, Maria Elena Crespo-Lopez, Alexei Verkhratsky
Summary: Microglial cells, originating from foetal macrophages, undergo phenotypic metamorphosis in response to the nervous tissue environment, displaying high plasticity and heterogeneity in gene and protein expression; their surveilling functions are crucial for maintaining homeostasis and contributing to the adaptive capacity of the central nervous system.
BIOLOGICAL REVIEWS
(2022)
Article
Neurosciences
Quentin Leyrolle, Fanny Decoeur, Cyril Dejean, Galadriel Briere, Stephane Leon, Ioannis Bakoyiannis, Emilie Baroux, Tony-Lee Sterley, Clementine Bosch-Bouju, Lydie Morel, Camille Amadieu, Cynthia Lecours, Marie-Kim St-Pierre, Maude Bordeleau, Veronique De Smedt-Peyrusse, Alexandran Sere, Leslie Schwendimann, Stephane Gregoire, Lionel Bretillon, Niyazi Acar, Corinne Joffre, Guillaume Ferreira, Raluca Uricaru, Patricia Thebault, Pierre Gressens, Marie-Eve Tremblay, Sophie Laye, Agnes Nadjar
Summary: Westernized dietary habits leading to reduced intake of n-3 PUFAs may be associated with neurodevelopmental disorders and disruptions in brain functional connectivity. Lifelong n-3 PUFA deficiency can interfere with oligodendrocyte maturation and myelination processes, resulting in long-term detrimental effects on white matter organization and hippocampus-prefrontal functional connectivity. Promoting developmental myelination through clemastine could rescue memory deficits in n-3 PUFA deficient animals.
Article
Neurosciences
Giorgio Corsi, Katherine Picard, Maria Amalia di Castro, Stefano Garofalo, Federico Tucci, Giuseppina Chece, Claudio del Percio, Maria Teresa Golia, Marcello Raspa, Ferdinando Scavizzi, Fanny Decoeur, Clotilde Lauro, Mara Rigamonti, Fabio Iannello, Davide Antonio Ragozzino, Eleonora Russo, Giovanni Bernardini, Agnes Nadjar, Marie Eve Tremblay, Claudio Babiloni, Laura Maggi, Cristina Limatola
Summary: Microglia play a crucial role in regulating sleep by adapting their cx3cr1 expression level and modulating synaptic activity in a phase-dependent manner. The findings suggest the importance of microglial cells in the homeostasis of cerebral parenchyma and the regulation of the sleep/wake cycle.
Article
Neurosciences
Bernadette Basilico, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, Ingrid Reverte, Caterina Sanchini, Maria C. Marrone, Maria Giubettini, Valeria De Turris, Debora Salerno, Stefano Garofalo, Marie-Kim St-Pierre, Micael Carrier, Massimiliano Renzi, Francesca Pagani, Brijesh Modi, Marcello Raspa, Ferdinando Scavizzi, Cornelius T. Gross, Silvia Marinelli, Marie-Eve Tremblay, Daniele Caprioli, Laura Maggi, Cristina Limatola, Silvia Di Angelantonio, Davide Ragozzino
Summary: The study reveals that microglia play an important role in regulating synaptic functioning in the adult brain, and their removal leads to reversible changes in the organization and activity of glutamatergic synapses.
Review
Pharmacology & Pharmacy
Eva Simoncicova, Elisa Goncalves de Andrade, Haley A. Vecchiarelli, Ifeoluwa O. Awogbindin, Charlotte Delage, Marie-Eve Tremblay
Summary: Microglia, as brain resident immune cells, play a crucial role in the development, activity, and plasticity of the central nervous system. They have been identified as potential targets for new neurotherapies due to their involvement in various neurological pathologies. Current research focuses on understanding the complex heterogeneity of microglia and developing more targeted treatments. Although the current therapies have limitations, clinical investigations are underway, and the future of microglial therapeutic research looks promising.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Correction
Neurosciences
Jonathan W. VanRyzin, Ashley E. Marquardt, Kathryn J. Argue, Haley A. Vecchiarelli, Sydney E. Ashton, E. Arambula, Matthew N. Hill, Margaret M. McCarthy
Article
Neurosciences
Haley A. Vecchiarelli, Maria Morena, Tiffany T. Y. Lee, Andrei S. Nastase, Robert J. Aukema, Kira D. Leitl, J. Megan Gray, Gavin N. Petrie, Kristin J. Tellez-Monnery, Matthew N. Hill
Summary: Research has shown that the endocannabinoid system plays a role in the neural and endocrine responses to stress. This study investigated how the endocannabinoid levels change in response to different acute stress modalities in male rats. The results suggest that there are sex differences in the dynamic responses of endocannabinoids to stress. These findings contribute to our understanding of the interactions between stress and endocannabinoid function.
NEUROBIOLOGY OF STRESS
(2022)
Review
Developmental Biology
Sophia M. Loewen, Adriano M. Chavesa, Colin J. Murray, Marianela E. Traetta, Sophia E. Burns, Keelin H. Pekarik, Marie-Eve Tremblay
Summary: Maternal immune activation (MIA) caused by various factors such as metabolic disorders, infections, and stress, is recognized as a major risk factor for neurodevelopmental disorders, especially with viral infections. MIA alters fetal development and triggers neurodevelopmental consequences, with microglia playing a crucial role. Animal models suggest that MIA disrupts important processes like synaptic pruning and cell proliferation/differentiation, and the COVID-19 pandemic may have implications for neurodevelopment. This review focuses on the impact of viral mimetic poly I:C-induced MIA on microglial functions and proposes approaches to prevent or mitigate MIA consequences.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Editorial Material
Neurosciences
Haley A. Vecchiarelli, Marie-eve Tremblay
Summary: Vasek et al. demonstrate that microglia engage in protein translation in their processes, which plays a crucial role in the number of processes and the formation of phagocytic cups. These findings shed light on the rapid response of microglia to diverse local signals in specific cellular compartments.
NATURE NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Victor Lau, Leanne Ramer, Marie-Eve Tremblay
Summary: Alzheimer's disease primarily involves neurodegeneration and cognitive decline, with progressive memory loss. Aging and other risk factors promote the accumulation of AD pathologies and inflammation. Glial senescence, particularly senescent microglia accumulation, contributes to the perpetuation of AD pathologies, glial aging, and further senescence. Increasing glial senescence is proposed to drive individuals from healthy cognition into cognitive decline and dementia.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Georgia Balsevich, Gavin N. Petrie, Daniel E. Heinz, Arashdeep Singh, Robert J. Aukema, Avery C. Hunker, Haley A. Vecchiarelli, Hiulan Yau, Martin Sticht, Roger J. Thompson, Francis S. Lee, Larry S. Zweifel, Prasanth K. Chelikani, Nils C. Gassen, Matthew N. Hill
Summary: A study found that the impact of FAAH C385A on metabolic outcomes is influenced by the environmental context. This genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a potential explanation for the conflicting findings in previous human studies.
Review
Pharmacology & Pharmacy
Chloe G. McKee, Madison Hoffos, Haley A. Vecchiarelli, Marie-Eve Tremblay
Summary: As individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive functions and to transitions toward mild cognitive impairment (MCI) and Alzheimer's disease (AD). Preclinical and early phase clinical trials investigating the therapeutic effects of pharmacological agents acting on microglia are currently underway, but important questions about target selectivity and microglial heterogeneity remain unanswered.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Michael J. Chrusch, Selena Fu, Simon C. Spanswick, Haley A. Vecchiarelli, Payal P. Patel, Matthew N. Hill, Richard H. Dyck
Summary: Zinc plays a role in modulating synaptic plasticity, particularly in the hippocampal dentate gyrus. This study aimed to determine if vesicular zinc is important for modulating adult hippocampal neurogenesis and behavior in an experience-dependent manner. The results show that vesicular zinc is essential for enhancing adult hippocampal neurogenesis and behavior following enrichment, supporting the role of zincergic neurons in experience-dependent plasticity in the hippocampus.
Editorial Material
Immunology
Haley A. Vecchiarelli, Marie-Eve Tremblay
BRAIN BEHAVIOR AND IMMUNITY
(2023)
