Review
Geriatrics & Gerontology
Qianting Deng, Chongyun Wu, Emily Parker, Timon Cheng-Yi Liu, Rui Duan, Luodan Yang
Summary: This article reviews the roles of microglia and astrocytes in Alzheimer's disease (AD) and emphasizes their importance in the pathogenesis and progression of AD. Research has found that these two types of glial cells play critical roles in neuroinflammation, synapse loss and pruning, clearance, and other processes related to AD. Therefore, therapeutic approaches targeting microglia and astrocytes may be promising for the treatment and prevention of AD.
Article
Immunology
Ji Wang, Hong-Sheng Chen, Hou-Hong Li, Hua-Jie Wang, Ruo-Si Zou, Xiao-Jia Lu, Jie Wang, Bin-Bin Nie, Jin-Feng Wu, Shuang Li, Bao-Ci Shan, Peng-Fei Wu, Li-Hong Long, Zhuang-Li Hu, Jian-Guo Chen, Fang Wang
Summary: Synapse loss in medial prefrontal cortex (mPFC) is implicated in stress-related mood disorders. Repeated longitudinal imaging of living brains reveals that both presynaptic and postsynaptic components decline, along with impaired synapse remodeling and cross-synaptic signal transmission during chronic stress. Chronic stress also induces excessive microglia phagocytosis, leading to the engulfment of excitatory synapses. Elevated complement C3 acts as a tag for synapse elimination by microglia. Moreover, chronic stress reduces the connectivity between mPFC and neighboring regions. Knockout of C3 reduces synaptic pruning and restores functional connectivity in mPFC, increasing resilience to chronic stress.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Multidisciplinary Sciences
Pablo Izquierdo, Hiroko Shiina, Chanawee Hirunpattarasilp, Grace Gillis, David Attwell
Summary: Microglia are immune cells in the central nervous system responsible for phagocytosing redundant synapses and debris. The THIK-1 K+ channels play a crucial role in regulating microglial phagocytosis and synaptic pruning. Changes in THIK-1 expression levels may impact neural circuit function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Suzanne S. Bohlson, Andrea J. Tenner
Summary: The complement system is an ancient collection of proteolytic cascades with well-defined roles in regulation of innate and adaptive immunity. With the convergence of a revolution in complement-directed clinical therapeutics, the discovery of specific complement-associated targetable pathways in the central nervous system, and the development of integrated multi-omic technologies that have all emerged over the last 15 years, precision therapeutic targeting in Alzheimer disease and other neurodegenerative diseases and processes appears to be within reach. As a sensor of tissue distress, the complement system protects the brain from microbial challenge as well as the accumulation of dead and/or damaged molecules and cells. Additional more recently discovered diverse functions of complement make it of paramount importance to design complement-directed neurotherapeutics such that the beneficial roles in neurodevelopment, adult neural plasticity, and neuroprotective functions of the complement system are retained.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Article
Neurosciences
Alexandros G. Kokkosis, Miguel M. Madeira, Zachary Hage, Kimonas Valais, Dimitris Koliatsis, Emran Resutov, Stella E. Tsirka
Summary: Chronic environmental stress and traumatic social experiences are risk factors for major depressive disorder and anxiety-related psychiatric disorders. Studies have shown that symptom severity is related to innate immune responses and upregulation of neuroinflammatory cytokine signaling in the brain's mood regulation areas. However, the role of microglia in modulating neuronal homeostasis in response to chronic stress has not been fully defined.
Article
Immunology
Xiaoming Zhang, Laura Kracht, Antonio M. Lerario, Marissa L. Dubbelaar, Nieske Brouwer, Evelyn M. Wesseling, Erik W. G. M. Boddeke, Bart J. L. Eggen, Susanne M. Kooistra
Summary: This study provides insight into epigenetic profiles and transcription factor networks associated with transcriptional signatures of tolerized and trained microglia in vivo, leading to a better understanding of innate immune memory of microglia.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Multidisciplinary Sciences
Nicole Scott-Hewitt, Youtong Huang, Beth Stevens
Summary: Changes in synaptic function are early indicators of neurological disorders, and microglia play a role in this process based on genetic, transcriptional, and epidemiological evidence. Environmental exposures and infections also contribute to alterations in neuroimmune interactions and synaptic changes. Recent studies across various neurological conditions have revealed common mechanisms underlying microglial-mediated synaptic dysfunction, suggesting that early microglial alterations may be a common factor contributing to synaptic pathologies.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biology
Keerthana Chithanathan, Fang-Ling Xuan, Miriam Ann Hickey, Li Tian
Summary: Compared to wildtype mice, 5 x FAD mice exhibited enhanced anxiety as early as 2 months old and showed increased pro-inflammatory cytokines in the olfactory bulb. The microglial activation and morphological changes were more prominent in the olfactory bulb of 2-month-old 5 x FAD mice. In the frontal cortex, pro-inflammatory cytokines were upregulated at a later stage (5-6 months old).
Review
Neurosciences
Yue Xiong, Jianhui Chen, Yingbo Li
Summary: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with unclear mechanisms. The role of microglia and astrocytes in ASD has gained attention, but the molecular link remains unknown. Previous studies have shown increased numbers of reactive microglia and astrocytes in ASD, highlighting their significant role. Understanding the roles of microglia and astrocytes in ASD is crucial for developing effective therapies. This review aimed to summarize their functions and contributions to ASD.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Food Science & Technology
Yihang Xing, Dingwen Zhang, Li Fang, Ji Wang, Chunlei Liu, Dan Wu, Xiaoting Liu, Xiyan Wang, Weihong Min
Summary: This paper discusses the role of C1q and the complement pathway in synaptic pruning during development, aging, and pathology, and their relevance to neurodegenerative diseases. It also summarizes the beneficial effects of certain foods on neurodegenerative diseases through C1q and the complement pathway, highlighting the need for further research.
Article
Cell Biology
Nivedita Hegdekar, Chinmoy Sarkar, Sabrina Bustos, Rodney M. M. Ritzel, Marie Hanscom, Prarthana Ravishankar, Deepika Philkana, Junfang Wu, David J. J. Loane, Marta M. M. Lipinski
Summary: Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) is associated with inhibited autophagy in neurons, microglia, and infiltrating macrophages. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 increases neuroinflammation after TBI, which is characterized by excessive activation of innate immune responses. Defects in microglial and macrophage autophagy following injury result in decreased clearance of danger/damage-associated molecular patterns, and inhibition of microglial/macrophage autophagy leads to increased neurodegeneration and worse cognitive outcomes.
Article
Neurosciences
Rajesh Kushwaha, Anshuman Sinha, Natallia Makarava, Kara Molesworth, Ilia V. Baskakov
Summary: This study demonstrated that reactive astrocytes in prion diseases have a neurotoxic effect on neuronal growth, dendritic spine development, and synapse maturation. Additionally, the conditioned media from reactive astrocytes was found to impair synapse integrity and reduce spine size and density, suggesting a synaptotoxic role of the reactive astrocyte phenotype associated with prion diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Annika Mordelt, Lot D. de Witte
Summary: There is a discussion about whether microglia are essential for healthy neurodevelopment, as reduced numbers or altered functions of microglia do not necessarily lead to neurodevelopmental disorders. Neuro-psychiatric symptoms seem to develop primarily in adulthood, challenging the concept associating microglia deficits with NDDs.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Review
Clinical Neurology
Agata Matejuk, Arthur A. Vandenbark, Halina Offner
Summary: The immune system plays a crucial role in maintaining tissue homeostasis and integrity, beyond self-recognition, from early development to ensure proper organ function later in life. Recent research shows that immune cells in the blood can support the CNS through neuroimmune communication, challenging the traditional view of peripheral immunity being detrimental to the nervous system. Understanding the cross-talk between the CNS and the immune system is essential to uncover neurodestructive and neuroprotective immune mechanisms for more effective therapeutic strategies in health and disease.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Eric Eyolfson, Thomas Carr, Erik Fraunberger, Asher Khan, Isabel Clark, Richelle Mychasiuk, Alexander W. Lohman
Summary: This study directly quantified the effects of repeated mild traumatic brain injuries (RmTBI) on adolescent and adult, male and female mice. The results revealed age- and sex-specific neurobehavioural deficits, microglia responses, and changes in dendritic spine density in select brain regions. The findings shed new light on the heterogeneity of RmTBI-induced behavioural and neuronal architecture changes dependent on age and sex.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Behavioral Sciences
Edna C. Cieslik, Markus Ullsperger, Martin Gell, Simon B. Eickhoff, Robert Langner
Summary: Previous studies on error processing have primarily focused on the posterior medial frontal cortex, but the role of other brain regions has been underestimated. This study used activation likelihood estimation meta-analyses to explore brain activity related to committing errors and responding successfully in interference tasks. It was found that the salience network and the temporoparietal junction were commonly involved in both correct and incorrect responses, indicating their general involvement in coping with situations that require increased cognitive control. Error-specific convergence was observed in the dorsal posterior cingulate cortex, posterior thalamus, and left superior frontal gyrus, while successful responding showed stronger convergence in the dorsal attention network and lateral prefrontal regions. Underrecruitment of these regions in error trials may reflect failures in activating the appropriate stimulus-response contingencies necessary for successful response execution.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2024)
