scholarly journals Lighting Up Ca2+ Dynamics in Animal Models

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2133
Author(s):  
Nelly Redolfi ◽  
Paloma García-Casas ◽  
Chiara Fornetto ◽  
Sonia Sonda ◽  
Paola Pizzo ◽  
...  
Keyword(s):  
Animal Models ◽  
Synaptic Transmission ◽  
Neurodegenerative Diseases ◽  
Neuronal Plasticity ◽  
Brain Function ◽  
Brain Research ◽  
Neuronal Survival ◽  
Neuronal Function ◽  
Brain Physiology

Calcium (Ca2+) signaling coordinates are crucial processes in brain physiology. Particularly, fundamental aspects of neuronal function such as synaptic transmission and neuronal plasticity are regulated by Ca2+, and neuronal survival itself relies on Ca2+-dependent cascades. Indeed, impaired Ca2+ homeostasis has been reported in aging as well as in the onset and progression of neurodegeneration. Understanding the physiology of brain function and the key processes leading to its derangement is a core challenge for neuroscience. In this context, Ca2+ imaging represents a powerful tool, effectively fostered by the continuous amelioration of Ca2+ sensors in parallel with the improvement of imaging instrumentation. In this review, we explore the potentiality of the most used animal models employed for Ca2+ imaging, highlighting their application in brain research to explore the pathogenesis of neurodegenerative diseases.

Astroglial contribution to tau-dependent neurodegeneration

2019 ◽  
Vol 476 (22) ◽  
pp. 3493-3504 ◽  
Author(s):  
Marta Sidoryk-Węgrzynowicz ◽  
Lidia Strużyńska
Keyword(s):  
Nervous System ◽  
Synaptic Transmission ◽  
Neurofibrillary Tangles ◽  
Neuronal Survival ◽  
Critical Role ◽  
Proper Function ◽  
Neuronal Dysfunction ◽  
Neuronal Function ◽  
Glutamate Homeostasis ◽  
The Brain

Astrocytes, by maintaining an optimal environment for neuronal function, play a critical role in proper function of mammalian nervous system. They regulate synaptic transmission and plasticity and protect neurons against toxic insults. Astrocytes and neurons interact actively via glutamine-glutamate cycle (GGC) that supports neuronal metabolic demands and neurotransmission. GGC deficiency may be involved in different diseases of the brain, where impaired astrocytic control of glutamate homeostasis contributes to neuronal dysfunction. This includes tau-dependent neurodegeneration, where astrocytes lose key molecules involved in regulation of glutamate/glutamine homeostasis, neuronal survival and synaptogenesis. Astrocytic dysfunction in tauopathy appears to precede neurodegeneration and overt tau neuropathology such as phosphorylation, aggregation and formation of neurofibrillary tangles. In this review, we summarize recent studies demonstrating that activation of astrocytes is strictly associated with neurodegenerative processes including those involved in tau related pathology. We propose that astrocytic dysfunction, by disrupting the proper neuron-glia signalling early in the disease, significantly contributes to tauopathy pathogenesis.

scholarly journals Is There a Brain Microbiome?

2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Ground Truth ◽  
Healthy Human ◽  
Strong Motivation ◽  
The Many ◽  
The Brain

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

scholarly journals Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8196
Author(s):  
Dorit Trudler ◽  
Swagata Ghatak ◽  
Stuart A. Lipton
Keyword(s):  
Drug Discovery ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Neural Function ◽  
Neural Cells ◽  
Human Samples ◽  
Healthy Donors ◽  
Induced Pluripotent

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

scholarly journals Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease

2021 ◽  
Author(s):  
Marina Betancor ◽  
Laura Moreno-Martínez ◽  
Óscar López-Pérez ◽  
Alicia Otero ◽  
Adelaida Hernaiz ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Prion Disease ◽  
Tetanus Toxin ◽  
Neuronal Survival ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Murine Models ◽  
Terminal Fragment ◽  
Lateral Sclerosis

AbstractThe non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

2016 ◽  
Vol 53 (2) ◽  
pp. 327-348 ◽  
Author(s):  
S. A. Youssef ◽  
M. T. Capucchio ◽  
J. E. Rofina ◽  
J. K. Chambers ◽  
K. Uchida ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Laboratory Animals ◽  
Aging Brain

Developments and new vistas in the field of melanocortins

2015 ◽  
Vol 6 (5-6) ◽  
pp. 361-382 ◽  
Author(s):  
Sheila Leone ◽  
Giorgio Noera ◽  
Alfio Bertolini
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Sexual Activity ◽  
Ischemia Reperfusion ◽  
Gouty Arthritis ◽  
Traumatic Injury ◽  
Large Body ◽  
Hypovolemic Shock ◽  
Therapeutic Effects ◽  
Tissue Ischemia

AbstractMelanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer’s disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.

scholarly journals Resolving rates of mutation in the brain using single-neuron genomics

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Gilad D Evrony ◽  
Eunjung Lee ◽  
Peter J Park ◽  
Christopher A Walsh
Keyword(s):  
Single Cell ◽  
Somatic Mutation ◽  
Brain Function ◽  
Single Neuron ◽  
Bioinformatic Analysis ◽  
Normal Brain ◽  
Neuronal Function ◽  
Human Neurons ◽  
Normal Brain Function ◽  
The Brain

Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (<xref ref-type="bibr" rid="bib65">Upton et al., 2015</xref>) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell, which is about fifty-fold lower than reported, confirming that L1 elements mobilize in some human neurons but indicating that L1 mosaicism is not ubiquitous. Through consideration of the challenges identified, we provide a foundation and framework for designing single-cell genomics studies.

scholarly journals Glycolytically impaired glial cells fuel neural metabolism via β-oxidation

2021 ◽  
Author(s):  
Stefanie Schirmeier ◽  
Helen Hertenstein ◽  
Ellen McMullen ◽  
Leon Deharde ◽  
Marko Brankatschk
Keyword(s):  
Glial Cells ◽  
Brain Function ◽  
Ketone Bodies ◽  
Carbohydrate Restriction ◽  
Neuronal Function ◽  
Adverse Conditions ◽  
Energy Stores ◽  
Metabolic Sensor ◽  
The Brain ◽  
Starvation Conditions

Abstract Neuronal function is highly energy demanding and thus requires efficient and constant metabolite delivery. Like their mammalian counterparts Drosophila glia are highly glycolytic and provide lactate to fuel neuronal metabolism. However, flies are able to survive for several weeks in the absence of glial glycolysis1. Here, we study how glial cells maintain sufficient nutrient supply to neurons under conditions of carbohydrate restriction. We show that glycolytically impaired glia switch to fatty acid breakdown via β-oxidation and provide ketone bodies as an alternate neuronal fuel. Moreover, flies also rely on glial β-oxidation under starvation conditions with glial loss of β-oxidation increasing susceptibility to starvation. Further, we show that glial cells act as a metabolic sensor in the brain and can induce mobilization of peripheral energy stores to ensure brain metabolic homeostasis. In summary, our study gives pioneering evidence on the importance of glial β-oxidation and ketogenesis for brain function, and survival, under adverse conditions, like malnutrition. The glial capacity to utilize lipids as an energy source seems to be conserved from flies to humans.

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