scholarly journals Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
María-Paz Viveros ◽  
Eva-María Marco ◽  
Ricardo Llorente ◽  
Meritxell López-Gallardo
Keyword(s):  
Synaptic Plasticity ◽  
Emotional Responses ◽  
Endocannabinoid System ◽  
Brain Structures ◽  
Brain Regions ◽  
In Vitro Models ◽  
Emotional Behavior ◽  
Cb1 Receptors ◽  
Emotional States

The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long- term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

scholarly journals The endocannabinoid system in modulating fear, anxiety, and stress

2020 ◽  
Vol 22 (3) ◽  
pp. 229-239
Keyword(s):  
Emotional Disorders ◽  
Stress Responses ◽  
Emotional Responses ◽  
Endocannabinoid System ◽  
Brain Structures ◽  
Therapeutic Implications ◽  
Cortical Areas ◽  
Prefrontal Cortical ◽  
Pathophysiological Role

The endocannabinoid system is widely expressed in the limbic system, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this system in the control of emotions. In this review, we update recent advances on the function of the endocannabinoid system in determining the value of fear-evoking stimuli and promoting appropriate behavioral responses for stress resilience. We also review the alterations in the activity of the endocannabinoid system during fear, stress, and anxiety, and the pathophysiological role of each component of this system in the control of these protective emotional responses that also trigger pathological emotional disorders. In spite of all the evidence, we have not yet taken advantage of the therapeutic implications of this important role of the endocannabinoid system, and possible future strategies to improve the treatment of these emotional disorders are discussed.

scholarly journals P62 accumulates through neuroanatomical circuits in response to tauopathy propagation

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
François-Xavier Blaudin de Thé ◽  
Benjamin Lassus ◽  
Ari W. Schaler ◽  
Stephanie L. Fowler ◽  
Chris N. Goulbourne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Brain Regions ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Neuron Models ◽  
Protein Clearance ◽  
Underlying Mechanisms ◽  
Tau Aggregation

AbstractIn Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.

BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers

1990 ◽  
Vol 259 (4) ◽  
pp. H1278-H1287 ◽  
Author(s):  
R. Kawai ◽  
Y. Sawada ◽  
M. Channing ◽  
A. H. Newman ◽  
K. C. Rice ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rank Order ◽  
Compartment Model ◽  
Brain Structures ◽  
Opiate Receptor ◽  
Brain Regions ◽  
Binding Model ◽  
Rapid Phase

The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.

scholarly journals μNeurocircuitry: Establishing in vitro models of neurocircuits with human neurons

TECHNOLOGY ◽  
2017 ◽  
Vol 05 (02) ◽  
pp. 87-97 ◽  
Author(s):  
Joseph A. Fantuzzo ◽  
Lidia De Filippis ◽  
Heather McGowan ◽  
Nan Yang ◽  
Yi-Han Ng ◽  
...  
Keyword(s):  
Human Brain ◽  
Cell Biology ◽  
Spatial Separation ◽  
Brain Regions ◽  
In Vitro Models ◽  
Patient Specific ◽  
Neuronal Markers ◽  
Human Neurons ◽  
Human Neuronal Cells

Neurocircuits in the human brain govern complex behavior and involve connections from many different neuronal subtypes from different brain regions. Recent advances in stem cell biology have enabled the derivation of patient-specific human neuronal cells of various subtypes for the study of neuronal function and disease pathology. Nevertheless, one persistent challenge using these human-derived neurons is the ability to reconstruct models of human brain circuitry. To overcome this obstacle, we have developed a compartmentalized microfluidic device, which allows for spatial separation of cell bodies of different human-derived neuronal subtypes (excitatory, inhibitory and dopaminergic) but is permissive to the spreading of projecting processes. Induced neurons (iNs) cultured in the device expressed pan-neuronal markers and subtype specific markers. Morphologically, we demonstrate defined synaptic contacts between selected neuronal subtypes by synapsin staining. Functionally, we show that excitatory neuronal stimulation evoked excitatory postsynaptic current responses in the neurons cultured in a separate chamber.

scholarly journals Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 967
Author(s):  
Catarina Chaves ◽  
Tuan-Minh Do ◽  
Céline Cegarra ◽  
Valérie Roudières ◽  
Sandrine Tolou ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Structures ◽  
Brain Regions ◽  
Brain Barrier ◽  
Brain Endothelium ◽  
Slc Transporters ◽  
Blood Brain ◽  
The Brain ◽  
Human Primate

The non-human primate (NHP)-brain endothelium constitutes an essential alternative to human in the prediction of molecule trafficking across the blood–brain barrier (BBB). This study presents a comparison between the NHP transcriptome of freshly isolated brain microcapillaries and in vitro-selected brain endothelial cells (BECs), focusing on important BBB features, namely tight junctions, receptors mediating transcytosis (RMT), ABC and SLC transporters, given its relevance as an alternative model for the molecule trafficking prediction across the BBB and identification of new brain-specific transport mechanisms. In vitro BECs conserved most of the BBB key elements for barrier integrity and control of molecular trafficking. The function of RMT via the transferrin receptor (TFRC) was characterized in this NHP-BBB model, where both human transferrin and anti-hTFRC antibody showed increased apical-to-basolateral passage in comparison to control molecules. In parallel, eventual BBB-related regional differences were Investig.igated in seven-day in vitro-selected BECs from five brain structures: brainstem, cerebellum, cortex, hippocampus, and striatum. Our analysis retrieved few differences in the brain endothelium across brain regions, suggesting a rather homogeneous BBB function across the brain parenchyma. The presently established NHP-derived BBB model closely mimics the physiological BBB, thus representing a ready-to-use tool for assessment of the penetration of biotherapeutics into the human CNS.

scholarly journals Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip

2017 ◽  
Vol 117 (3) ◽  
pp. 1320-1341 ◽  
Author(s):  
Stephanie Dauth ◽  
Ben M. Maoz ◽  
Sean P. Sheehy ◽  
Matthew A. Hemphill ◽  
Tara Murty ◽  
...  
Keyword(s):  
Brain Function ◽  
Brain Regions ◽  
In Vitro Models ◽  
Comparative Data ◽  
Brain Areas ◽  
Functional Connections ◽  
Essential Components ◽  
The Brain

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections.

scholarly journals ANALYSIS OF THE ANTIOXIDANT ACTIVITY OF GERANIOL EMPLOYING VARIOUS IN-VITRO MODELS: RELEVANCE TO NEURODEGENERATION IN DIABETIC NEUROPATHY

2017 ◽  
Vol 10 (7) ◽  
pp. 101 ◽  
Author(s):  
Sathya N Prasad ◽  
Murali Muralidhara
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Activity ◽  
Rat Brain ◽  
Neuroblastoma Cell ◽  
Brain Regions ◽  
In Vitro Models ◽  
Human Neuroblastoma Cell ◽  
Pathological Feature ◽  
Human Neuroblastoma

Objective: The aim of this study was to analyze antioxidant effect of geraniol (GE) in different in vitro models.Methods: Initially, the antioxidant activity of GE was assessed by diphenyl picrylhydrazyl radical (DPPH) assay. The modulatory effect of GE against 2,2’-azobis(2-amidinopropane) dihydrochloride induced lipid peroxidation in rat brain regions (cortex and cerebellum) and sciatic nerve (SN) homogenates was determined. Further, the effect of GE was assessed against hyperglycemia-induced oxidative stress (OS) in SHSY5Y, a human neuroblastoma cell line.Results: GE proved to be a good scavenger of DPPH free radical (inhibitory concentration 50% [IC50] value = 663 nmol) and could lower the lipid peroxidation levels in rat brain tissue and SN homogenates (25-40%). Further, it rescue the SHSY5Y cells from hyperglycemia-induced death. Co-exposure of GE with the IC50 level of glucose (100 mM) lowered the levels of reactive oxygen species, hydrogen peroxides and 3-nitrotyrosine levels with concomitant elevation in the glutathione levels (about two folds).Conclusion: Collectively from these findings and other studies previously conducted (from our lab and others) emphasize the potential benefit of GE against OS, a progressive pathological feature of neurodegenerative disorders. 

Analysis and applicability of different in vitro models of Glioblastoma multiforme

2014 ◽  
Vol 226 (06) ◽  
Author(s):  
D William ◽  
M Linnebacher ◽  
CF Classen
Keyword(s):  
Glioblastoma Multiforme ◽  
In Vitro Models
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