scholarly journals Regulation of Reelin functions by specific proteolytic processing in the brain

2021 ◽  
Author(s):  
Mitsuharu Hattori ◽  
Takao Kohno
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Proteolytic Processing ◽  
Postnatal Brain ◽  
Dendrite Development ◽  
Mature Brain ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
The Brain

Abstract The secreted glycoprotein Reelin plays important roles in both brain development and function. During development, Reelin regulates neuronal migration and dendrite development. In the mature brain, the glycoprotein is involved in synaptogenesis and synaptic plasticity. It has been suggested that Reelin loss or decreased function contributes to the onset and/or deterioration of neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease. While the molecular mechanisms underpinning Reelin function remain unclear, recent studies have suggested that the specific proteolytic cleavage of Reelin may play central roles in the embryonic and postnatal brain. In this review, we focus on Reelin proteolytic processing and review its potential physiological roles.

scholarly journals Molekulare Kontrolle der Stabilität und Plastizität von Synapsen

BIOspektrum ◽  
2021 ◽  
Vol 27 (6) ◽  
pp. 588-590
Author(s):  
Zeeshan Mushtaq ◽  
Jan Pielage
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Information Flow ◽  
Molecular Mechanisms ◽  
Synaptic Connectivity ◽  
Genetic Mutations ◽  
Neuronal Circuits ◽  
The Brain

AbstractThe precise regulation of synaptic connectivity is essential for the processing of information in the brain. Any aberrant loss of synaptic connectivity due to genetic mutations will disrupt information flow in the nervous system and may represent the underlying cause of psychiatric or neurodegenerative diseases. Therefore, identification of the molecular mechanisms controlling synaptic plasticity and maintenance is essential for our understanding of neuronal circuits in development and disease.

scholarly journals Probing the VIPR2 Microduplication Linkage to Schizophrenia in Animal and Cellular Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Yukio Ago ◽  
Satoshi Asano ◽  
Hitoshi Hashimoto ◽  
James A. Waschek
Keyword(s):  
Synaptic Plasticity ◽  
Brain Development ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Autism Spectrum ◽  
Cellular Models ◽  
Pituitary Adenylate Cyclase ◽  
Innervation Patterns ◽  
The Brain

Pituitary adenylate cyclase-activating polypeptide (PACAP, gene name ADCYAP1) is a multifunctional neuropeptide involved in brain development and synaptic plasticity. With respect to PACAP function, most attention has been given to that mediated by its specific receptor PAC1 (ADCYAP1R1). However, PACAP also binds tightly to the high affinity receptors for vasoactive intestinal peptide (VIP, VIP), called VPAC1 and VPAC2 (VIPR1 and VIPR2, respectively). Depending on innervation patterns, PACAP can thus interact physiologically with any of these receptors. VPAC2 receptors, the focus of this review, are known to have a pivotal role in regulating circadian rhythms and to affect multiple other processes in the brain, including those involved in fear cognition. Accumulating evidence in human genetics indicates that microduplications at 7q36.3, containing VIPR2 gene, are linked to schizophrenia and possibly autism spectrum disorder. Although detailed molecular mechanisms have not been fully elucidated, recent studies in animal models suggest that overactivation of the VPAC2 receptor disrupts cortical circuit maturation. The VIPR2 linkage can thus be potentially explained by inappropriate control of receptor signaling at a time when neural circuits involved in cognition and social behavior are being established. Alternatively, or in addition, VPAC2 receptor overactivity may disrupt ongoing synaptic plasticity during processes of learning and memory. Finally, in vitro data indicate that PACAP and VIP have differential activities on the maturation of neurons via their distinct signaling pathways. Thus perturbations in the balance of VPAC2, VPAC1, and PAC1 receptors and their ligands may have important consequences in brain development and plasticity.

scholarly journals Microglia in the developing retina

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Fenge Li ◽  
Danye Jiang ◽  
Melanie A. Samuel
Keyword(s):  
Molecular Mechanisms ◽  
Neuron Development ◽  
Laminar Organization ◽  
Retina Development ◽  
Retinal Microglia ◽  
Mammalian Retina ◽  
Underlying Mechanisms ◽  
And Function ◽  
Neuron Function ◽  
The Brain

AbstractMicroglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron function remain poorly understood in part because such analysis is challenging in the brain where neurons and synapses are intermingled and connectivity is only beginning to be mapped. Here, we discuss the features and function of microglia in the ordered mammalian retina where the laminar organization of neurons and synapses facilitates such molecular studies. We discuss microglia origins and consider the evidence for molecularly distinct microglia subpopulations and their potential for differential roles with a particular focus on the early stages of retina development. We then review the models and methods used for the study of these cells and discuss emerging data that link retina microglia to the genesis and survival of particular retina cell subtypes. We also highlight potential roles for microglia in shaping the development and organization of the vasculature and discuss cellular and molecular mechanisms involved in this process. Such insights may help resolve the mechanisms by which retinal microglia impact visual function and help guide studies of related features in brain development and disease.

scholarly journals Expression and role of Galectin-3 in the postnatal development of the cerebellum

2018 ◽  
Author(s):  
Inés González-Calvo ◽  
Fekrije Selimi
Keyword(s):  
Synaptic Plasticity ◽  
Immune System ◽  
Purkinje Cell ◽  
Axon Guidance ◽  
Neuronal Migration ◽  
Neural Circuits ◽  
Related Protein ◽  
Galectin 3 ◽  
The Brain

AbstractMany proteins initially identified in the immune system play roles in neurogenesis, neuronal migration, axon guidance, synaptic plasticity and other processes related to the formation and refinement of neural circuits. Although the function of the immune-related protein Galectin-3 (LGALS3) has been extensively studied in the regulation of inflammation, cancer and microglia activation, little is known about its role in the development of the brain. In this study, we identified that LGALS3 is expressed in the developing postnatal cerebellum. More precisely, LGALS3 is expressed by cells in meninges and in the choroid plexus, and in subpopulations of astrocytes and of microglial cells in the cerebellar cortex. Analysis of Lgals3 knockout mice showed that Lgals3 is dispensable for the development of cerebellar cytoarchitecture and Purkinje cell excitatory synaptogenesis in the mouse.

scholarly journals Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

2020 ◽  
Vol 8 ◽  
Author(s):  
Yu Rim Kim ◽  
Young Min Kim ◽  
Jaeho Lee ◽  
Joohyun Park ◽  
Jong Eun Lee ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Neutrophil Infiltration ◽  
Two Photon ◽  
Activated State ◽  
The Central Nervous System ◽  
Time Observation ◽  
And Function ◽  
The Brain

The circulatory neutrophil and brain tissue-resident microglia are two important immune cells involved in neuroinflammation. Since neutrophils that infiltrate through the brain vascular vessel may affect the immune function of microglia in the brain, close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and immunological aftermaths that follow. This study aimed to observe how morphology and function of both neutrophils and microglia are converted in the inflamed brain. To directly investigate cellular responses of neutrophils and microglia, LysMGFP/+ and CX3CR1GFP/+ mice were used for the observation of neutrophils and microglia, respectively. In addition, low-dose lipopolysaccharide (LPS) was utilized to induce acute inflammation in the central nervous system (CNS) of mice. Real-time observation on mice brain undergoing neuroinflammation via two-photon intravital microscopy revealed various changes in neutrophils and microglia; namely, neutrophil infiltration and movement within the brain tissue increased, while microglia displayed morphological changes suggesting an activated state. Furthermore, neutrophils seemed to not only actively interact with microglial processes but also exhibit reverse transendothelial migration (rTEM) back to the bloodstream. Thus, it may be postulated that, through crosstalk with neutrophils, macrophages are primed to initiate a neuroinflammatory immune response; also, during pathogenic events in the brain, neutrophils that engage in rTEM may deliver proinflammatory signals to peripheral organs outside the brain. Taken together, these results both show that neuroinflammation results in significant alterations in neutrophils and microglia and lay the pavement for further studies on the molecular mechanisms behind such changes.

scholarly journals Glycosphingolipids and neuroinflammation in Parkinson’s disease

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Karim Belarbi ◽  
Elodie Cuvelier ◽  
Marie-Amandine Bonte ◽  
Mazarine Desplanque ◽  
Bernard Gressier ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Inflammasome Activation ◽  
Nigrostriatal Pathway ◽  
Neurodegenerative Process ◽  
And Function ◽  
The Brain

Abstract Parkinson's disease is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons of the nigrostriatal pathway and the formation of neuronal inclusions known as Lewy bodies. Chronic neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. Glycosphingolipids are a well-defined subclass of lipids that regulate crucial aspects of the brain function and recently emerged as potent regulators of the inflammatory process. Deregulation in glycosphingolipid metabolism has been reported in Parkinson’s disease. However, the interrelationship between glycosphingolipids and neuroinflammation in Parkinson’s disease is not well known. This review provides a thorough overview of the links between glycosphingolipid metabolism and immune-mediated mechanisms involved in neuroinflammation in Parkinson’s disease. After a brief presentation of the metabolism and function of glycosphingolipids in the brain, it summarizes the evidences supporting that glycosphingolipids (i.e. glucosylceramides or specific gangliosides) are deregulated in Parkinson’s disease. Then, the implications of these deregulations for neuroinflammation, based on data from human inherited lysosomal glycosphingolipid storage disorders and gene-engineered animal studies are outlined. Finally, the key molecular mechanisms by which glycosphingolipids could control neuroinflammation in Parkinson’s disease are highlighted. These include inflammasome activation and secretion of pro-inflammatory cytokines, altered calcium homeostasis, changes in the blood-brain barrier permeability, recruitment of peripheral immune cells or production of autoantibodies.

scholarly journals Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and Cardiovascular Disorders

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Sébastien S. Hébert
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Heart Cell ◽  
Cardiovascular Disorders ◽  
Increased Risk ◽  
Mirna Expression Profiles ◽  
And Function ◽  
The Brain

Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure. Here, the hypothesis of how miRNA-regulated pathways could contribute to comorbid neurological and cardiovascular disorders will be discussed. Presentation. Changes in miRNA expression occurring in the brain and heart could have an impact on coexisting neurological and cardiovascular characteristics by (1) modulating organ function, (2) accentuating cellular stress, and (3) impinging on neuronal and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in the brain and heart tissues from individuals with comorbid neurodegenerative and cardiovascular disorders will be of great importance and relevance. Implications. Careful experimental design will shed light to the deeper understanding of the molecular mechanisms tying up those different but yet somehow connected diseases.

scholarly journals Autism: A “Critical Period” Disorder?

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jocelyn J. LeBlanc ◽  
Michela Fagiolini
Keyword(s):  
Critical Period ◽  
Molecular Mechanisms ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behaviors ◽  
Postnatal Life ◽  
Critical Periods ◽  
Restricted Interests ◽  
Behavioral Impairments ◽  
And Function ◽  
The Brain

Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I) neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits.

scholarly journals Synapse formation: from cellular and molecular mechanisms to neurodevelopmental and neurodegenerative disorders

2019 ◽  
Vol 121 (4) ◽  
pp. 1381-1397 ◽  
Author(s):  
Shadab Batool ◽  
Hussain Raza ◽  
Jawwad Zaidi ◽  
Saba Riaz ◽  
Sean Hasan ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Brain Functions ◽  
Mature Brain ◽  
Behavioral Needs ◽  
Neuronal Assembly ◽  
The Brain ◽  
Shed Light

The precise patterns of neuronal assembly during development determine all functional outputs of a nervous system; these may range from simple reflexes to learning, memory, cognition, etc. To understand how brain functions and how best to repair it after injury, disease, or trauma, it is imperative that we first seek to define fundamental steps mediating this neuronal assembly. To acquire the sophisticated ensemble of highly specialized networks seen in a mature brain, all proliferated and migrated neurons must extend their axonal and dendritic processes toward targets, which are often located at some distance. Upon contact with potential partners, neurons must undergo dramatic structural changes to become either a pre- or a postsynaptic neuron. This connectivity is cemented through specialized structures termed synapses. Both structurally and functionally, the newly formed synapses are, however, not static as they undergo consistent changes in order for an animal to meet its behavioral needs in a changing environment. These changes may be either in the form of new synapses or an enhancement of their synaptic efficacy, referred to as synaptic plasticity. Thus, synapse formation is not restricted to neurodevelopment; it is a process that remains active throughout life. As the brain ages, either the lack of neuronal activity or cell death render synapses dysfunctional, thus giving rise to neurodegenerative disorders. This review seeks to highlight salient steps that are involved in a neuron’s journey, starting with the establishment, maturation, and consolidation of synapses; we particularly focus on identifying key players involved in the synaptogenic program. We hope that this endeavor will not only help the beginners in this field to understand how brain networks are assembled in the first place but also shed light on various neurodevelopmental, neurological, neurodegenerative, and neuropsychiatric disorders that involve synaptic inactivity or dysfunction.

Monoamines: Dopamine, Norepinephrine, and Serotonin, Beyond Modulation, “Switches” That Alter the State of Target Networks

2020 ◽  
pp. 107385842097433
Author(s):  
Sayed Ausim Azizi
Keyword(s):  
Nervous System ◽  
Information Processing ◽  
Brain Function ◽  
Anatomy And Physiology ◽  
Neuropsychiatric Diseases ◽  
Brain States ◽  
Brain Operations ◽  
And Function ◽  
Electrophysiological Effects ◽  
The Brain

How do monoamines influence the perceptual and behavioral aspects of brain function? A library of information regarding the genetic, molecular, cellular, and function of monoamines in the nervous system and other organs has accumulated. We briefly review monoamines’ anatomy and physiology and discuss their effects on the target neurons and circuits. Monoaminergic cells in the brain stem receive inputs from sensory, limbic, and prefrontal areas and project extensively to the forebrain and hindbrain. We review selected studies on molecular, cellular, and electrophysiological effects of monoamines on the brain’s target areas. The idea is that monoamines, by reversibly modulating the “primary” information processing circuits, regulate and switch the functions of brain networks and can reversibly alter the “brain states,” such as consciousness, emotions, and movements. Monoamines, as the drivers of normal motor and sensory brain operations, including housekeeping, play essential roles in pathogenesis of neuropsychiatric diseases.

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