scholarly journals Interneuron Dysfunction in Syndromic Autism: Recent Advances

2015 ◽  
Vol 37 (6) ◽  
pp. 467-475 ◽  
Author(s):  
Tomoyuki Takano
Keyword(s):  
Experimental Models ◽  
Aminobutyric Acid ◽  
Inhibitory Interneurons ◽  
Gabaergic Interneurons ◽  
Inhibitory Mechanism ◽  
Future Studies ◽  
Recent Advances ◽  
Syndromic Autism ◽  
The Relationship ◽  
The Brain

Autism is an extremely heterogeneous disorder, but its frequent cooccurrence with epilepsy leads to speculation that there may be common mechanisms associated with these disorders. Inhibitory interneurons are considered to be the main cellular elements that control hyperexcitability in the brain, and interneuron dysfunction can cause pathological hyperexcitability linked to seizure susceptibility or epilepsy. This review summarizes some of the recent advances that support the relationship between interneuron dysfunction and cognitive impairment in human syndromic autism, with particular reference to the pathophysiological findings of murine experimental models of autism. Alterations in γ-aminobutyric acid (GABA)ergic circuits include a wide variety of neurobiological dysfunctions and do not simply involve the loss or gain of any given type of inhibitory mechanism. The characteristics of interneuron dysfunction in each murine model of autism differ for each syndrome, and these diversities may be due to differences in genetic backgrounds or some other currently unknown variances. Future studies should give us a greater understanding of the involvement of different classes of GABAergic interneurons and allow us to define the relationship between the precise pathophysiological mechanisms and the corresponding clinical phenotypes in autism.

Involvement of NLRP3 inflammasome in schizophrenia-like behaviour in young animals after maternal immune activation

2020 ◽  
Vol 32 (6) ◽  
pp. 321-327
Author(s):  
Letícia Ventura ◽  
Viviane Freiberger ◽  
Vinicius B. Thiesen ◽  
Paula Dias ◽  
Matheus L. Dutra ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Immune Activation ◽  
Nlrp3 Inflammasome ◽  
Biochemical Analysis ◽  
Future Studies ◽  
Maternal Immune Activation ◽  
Pyrin Domain ◽  
Behavioural Tests ◽  
The Relationship ◽  
The Brain

AbstractObjective:To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA).Methods:To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements.Results:It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1β levels on 7, 14 and 45 postnatal days.Conclusion:This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

scholarly journals GABAergic Interneurons in Seizures: Investigating Causality With Optogenetics

2018 ◽  
Vol 25 (4) ◽  
pp. 344-358 ◽  
Author(s):  
Vincent Magloire ◽  
Marion S. Mercier ◽  
Dimitri M. Kullmann ◽  
Ivan Pavlov
Keyword(s):  
Imaging Techniques ◽  
Epileptiform Activity ◽  
Cell Types ◽  
Inhibitory Interneurons ◽  
Gabaergic Interneurons ◽  
Epileptic Discharges ◽  
Recent Developments ◽  
First Time ◽  
The Brain

Seizures are complex pathological network events characterized by excessive and hypersynchronized activity of neurons, including a highly diverse population of GABAergic interneurons. Although the primary function of inhibitory interneurons under normal conditions is to restrain excitation in the brain, this system appears to fail intermittently, allowing runaway excitation. Recent developments in optogenetics, combined with genetic tools and advanced electrophysiological and imaging techniques, allow us for the first time to assess the causal roles of identified cell-types in network dynamics. While these methods have greatly increased our understanding of cortical microcircuits in epilepsy, the roles played by individual GABAergic cell-types in controlling ictogenesis remain incompletely resolved. Indeed, the ability of interneurons to suppress epileptic discharges varies across different subtypes, and an accumulating body of evidence paradoxically implicates some interneuron subtypes in the initiation and maintenance of epileptiform activity. Here, we bring together findings from this growing field and discuss what can be inferred regarding the causal role of different GABAergic cell-types in seizures.

Grenzenlose Verantwortung

2010 ◽  
Vol 2010 (1) ◽  
pp. 5-22
Author(s):  
Ralf Becker
Keyword(s):  
Personal Freedom ◽  
The Relationship ◽  
The Brain

The article examines the relationship between freedom, guilt and responsibility in Dostojewski’s and Sartre’s works. Both attribute a great measure of personal freedom to man. Therefore, they do not tolerate excuses. Whoever is free, carries responsibility and gets caught up in guilt. Dostojewski’s focus is mainly on guilt, Sartre’s is on responsibility. They share the conviction that we can delegate responsibility for our actions or our way of living neither to a whole, of which we are a part, like society (the ,milieu'), nor to a part, for which we are the whole, like the ,brain' or the ,genes'. In that sense, Dostojewski’s and Sartre’s attempts at an ethic of responsibility also offer convincing arguments against determinism.

EXPERIMENTAL ASSESSMENT OF THE NANOPARTICLES TOXICITY OF NICKEL OXIDE IN TWO SIZES IN THE SUBCHRONIC EXPERIMENT

2018 ◽  
pp. 30-35
Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Nervous Activity ◽  
Equal Mass ◽  
The Body ◽  
Subchronic Toxicity ◽  
Physiological Mechanisms ◽  
Nickel Oxide Nanoparticles ◽  
The Relationship ◽  
The Brain ◽  
Nanoparticles Toxicity

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.

Polymeric Nanoparticles for Brain Drug Delivery - A Review

2020 ◽  
Vol 21 (9) ◽  
pp. 649-660
Author(s):  
Subashini Raman ◽  
Syed Mahmood ◽  
Ayah R. Hilles ◽  
Md Noushad Javed ◽  
Motia Azmana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Preparation Methods ◽  
Brain Drug Delivery ◽  
Polymeric Nanoparticle ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

Drusen in the Peripheral Retina of the Alzheimer’s Eye

2018 ◽  
Vol 15 (8) ◽  
pp. 743-750 ◽  
Author(s):  
Kresimir Ukalovic ◽  
Sijia Cao ◽  
Sieun Lee ◽  
Qiaoyue Tang ◽  
Mirza Faisal Beg ◽  
...  
Keyword(s):  
Peripheral Retina ◽  
Amyloid Angiopathy ◽  
Temporal Region ◽  
Future Studies ◽  
Eye Tissues ◽  
Neuropathological Diagnosis ◽  
Ocular Imaging ◽  
Cerebral Amyloid ◽  
The Brain ◽  
Oil Red O

Background: Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD. Objective: This study compares macular and peripheral drusen load in control and AD eyes. Methods: Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (<55 years) and older (>55 years) groups. After fixation and dissection, 3-6 mm punches of RPE/choroid were taken in macular and peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive drusen were counted and grouped into two size categories: small (<63 μm) and intermediate (63-125 μm). Results: There was a significant increase in the total number of macular and peripheral hard drusen in older, compared to younger, normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes, even after controlling for age (p<0.05). Among the brain and eye tissues from AD donors, there was a significant relationship between cerebral amyloid angiopathy (CAA) severity and number of temporal intermediate hard drusen (r=0.78, p<0.05). Conclusion: Imaging temporal drusen in the eye may have benefit for diagnosing and monitoring progression of AD. Our results on CAA severity and temporal intermediate drusen in the AD eye are novel. Future studies are needed to further understand the interactions among CAA and drusen formation.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

New Work on Speech Acts

2018 ◽  
Keyword(s):  
Speech Acts ◽  
Speech Act ◽  
Speech Act Theory ◽  
New Work ◽  
Half Century ◽  
Recent Advances ◽  
Current Thinking ◽  
Semantics And Pragmatics ◽  
Recent Developments ◽  
The Relationship

The essays collected in this book represent recent advances in our understanding of speech acts-actions like asserting, asking, and commanding that speakers perform when producing an utterance. The study of speech acts spans disciplines, and embraces both the theoretical and scientific concerns proper to linguistics and philosophy as well as the normative questions that speech acts raise for our politics, our societies, and our ethical lives generally. It is the goal of this book to reflect the diversity of current thinking on speech acts as well as to bring these conversations together, so that they may better inform one another. Topics explored in this book include the relationship between sentence grammar and speech act potential; the fate of traditional frameworks in speech act theory, such as the content-force distinction and the taxonomy of speech acts; and the ways in which speech act theory can illuminate the dynamics of hostile and harmful speech. The book takes stock of well over a half century of thinking about speech acts, bringing this classicwork in linewith recent developments in semantics and pragmatics, and pointing the way forward to further debate and research.

scholarly journals The relationship of morphometric changes of the brain with IL-6 levels, systemic inflammation and immune disturbances in the patients with schizophrenia

2021 ◽  
Vol 190 ◽  
pp. 553-559
Author(s):  
Irina K. Malashenkova ◽  
Vadim L. Ushakov ◽  
Sergey A. Krynskiy ◽  
Daniil P. Ogurtsov ◽  
Nikita A. Khailov ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

scholarly journals Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice

2021 ◽  
Author(s):  
Kinga K. Borowicz-Reutt ◽  
Monika Banach ◽  
Monika Rudkowska ◽  
Anna Stachniuk
Keyword(s):  
Antiepileptic Drugs ◽  
Second Generation ◽  
Antidepressant Drug ◽  
Experimental Models ◽  
Long Term Memory ◽  
Avoidance Task ◽  
Maximal Electroshock ◽  
Term Memory ◽  
The Brain

Abstract Background Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. Materials and methods As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. Results Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. Conclusion Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

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