scholarly journals Pathological investigation of neuroprotective activity of new derivatives of fused pyrazolyl-thienopyridines in Corazol-induced seizures

2021 ◽  
Vol 10 (4) ◽  
pp. 53-62
Author(s):  
H.V. Gasparyan ◽  
◽  
S.A. Buloyan ◽  
A.E. Pogosyan ◽  
L.M. Arshakyan ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Glial Cells ◽  
Histopathological Examination ◽  
Neuronal Loss ◽  
Brain Structures ◽  
Neuroprotective Activity ◽  
Morphological Alterations ◽  
Ca1 Region ◽  
Derivatives Of ◽  
The Brain

Introduction. Seizures provoke several morphological alterations in the brain structures. These alterations are primarily located in the hippocampal CA1 region and the entorhinal cortex. Recurrent seizures are common in patients with epilepsy. Therapeutic options for this disease are very limited and most of them are aimed at relieving symptoms. In most cases, to treat epilepsy, anti-seizure drugs are used. Nevertheless, one-third of affected individuals have resistance to them. Thus, the study of new effective agents that can prevent epileptogenesis is still an ongoing challenge. In this work, we aimed to study the neuroprotective activity of several new derivatives of tricyclic pyrazolyl substituted thieno[2,3-c]isoquinolins (SHD-89 and SHD-91) and pyrano[4,3-d]thieno[2,3-b]pyridines (SHD-78 and SHD-85) as potential anti-seizure drugs. Materials and methods. The study was performed on mice (n=60). The action of compounds SHD-78, SHD-85, SHD-89, and SHD-91 was tested in seizures with and without Corazol administration. Histopathological examinations were performed in the hippocampus and the entorhinal cortex in different experimental groups. Results. The study showed that under the action of SHD-89 and SHD-78, there was a reduction in the number of neurons and activation of glial cells in examined regions of the brain. SHD-91 caused severe neurode-generative effects with changes in the brain structure. In contrast, under the action of SHD-85, the number of neurons was higher and with lower activation of glial cells. Conclusion. Studies showed that among the tested compounds SHD-85 possessed moderate neuroprotective activity and reduced gliosis and neuronal loss induced by Corazol. Keywords: anti-seizure drugs, pyrazolylthienopyridines, hippocampus, entorhinal cortex, histopathological examination

scholarly journals Effects of cadmium on the glial architecture in lizard brain

2017 ◽  
Author(s):  
Rossana Favorito ◽  
Antonio Monaco ◽  
Maria C. Grimaldi ◽  
Ida Ferrandino
Keyword(s):  
Blood Brain Barrier ◽  
Glial Cells ◽  
Toxic Metal ◽  
Chemical Exposure ◽  
Brain Barrier ◽  
Cresyl Violet ◽  
Cytotoxic Action ◽  
Morphological Alterations ◽  
Blood Brain ◽  
The Brain

The glial cells are positioned to be the first cells of the brain parenchyma to face molecules crossing the blood-brain barrier with a relevant neuroprotective role from cytotoxic action of heavy metals on the nervous system. Cadmium is a highly toxic metal and its levels in the environment are increasing due to industrial activities. This element can pass the blood-brain barrier and have neurotoxic activity. For this reason we have studied the effects of cadmium on the glial architecture in the lizard Podarcis siculus, a significant bioindicator of chemical exposure due to its persistence in a variety of habitats. The study was performed on two groups of lizards. The first group of P. siculus was exposed to an acute treatment by a single i.p. injection (2 mg/kg-BW) of CdCl2 and sacrificed after 2, 7 and 16 days. The second one was used as control. The histology of the brain was studied by Hematoxylin/Eosin and Cresyl/Violet stains while the glial structures were analyzed by immunodetection of the glial fibrillary acidic protein (GFAP), the most widely accepted marker for astroglial cells. Evident morphological alterations of the brain were observed at 7 and 16 days from the injection, when we revealed also a decrease of the GFAP-immunopositive structures in particular in the rhombencephalic ventricle, telencephalon and optic tectum. These results show that in the lizards an acute exposure to cadmium provokes morphological cellular alterations in the brain but also a decrement of the expression of GFAP marker with possible consequent damage of glial cells functions.

scholarly journals Critical Molecular and Cellular Contributors to Tau Pathology

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 190
Author(s):  
Liqing Song ◽  
Evan A. Wells ◽  
Anne Skaja Robinson
Keyword(s):  
Signaling Pathways ◽  
Glial Cells ◽  
Early Stage ◽  
Neuronal Loss ◽  
Disease Spread ◽  
Tau Pathology ◽  
Neuroprotective Effects ◽  
Inflammatory Microenvironment ◽  
Mapt Gene ◽  
The Brain

Tauopathies represent a group of neurodegenerative diseases including Alzheimer’s disease (AD) that are characterized by the deposition of filamentous tau aggregates in the brain. The pathogenesis of tauopathies starts from the formation of toxic ‘tau seeds’ from hyperphosphorylated tau monomers. The presence of specific phosphorylation sites and heat shock protein 90 facilitates soluble tau protein aggregation. Transcellular propagation of pathogenic tau into synaptically connected neuronal cells or adjacent glial cells via receptor-mediated endocytosis facilitate disease spread through the brain. While neuroprotective effects of glial cells—including phagocytotic microglial and astroglial phenotypes—have been observed at the early stage of neurodegeneration, dysfunctional neuronal-glial cellular communication results in a series of further pathological consequences as the disease progresses, including abnormal axonal transport, synaptic degeneration, and neuronal loss, accompanied by a pro-inflammatory microenvironment. Additionally, the discovery of microtubule-associated protein tau (MAPT) gene mutations and the strongest genetic risk factor of tauopathies—an increase in the presence of the ε2 allele of apolipoprotein E (ApoE)—provide important clues to understanding tau pathology progression. In this review, we describe the crucial signaling pathways and diverse cellular contributors to the progression of tauopathies. A systematic understanding of disease pathogenesis provides novel insights into therapeutic targets within altered signaling pathways and is of great significance for discovering effective treatments for tauopathies.

scholarly journals The effect of new derivatives of tietan-1,1-dioxide on some mediator systems of the brain

2012 ◽  
Vol 93 (1) ◽  
pp. 108-112
Author(s):  
O A Ivanova ◽  
I L Nikitina ◽  
E K Alekhin ◽  
A F Miftahova
Keyword(s):  
Antidepressant Activity ◽  
Brain Structures ◽  
Antidepressant Effect ◽  
Pharmacological Interaction ◽  
Dopamine Receptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Mediator Systems ◽  
Depth Study ◽  
Derivatives Of ◽  
The Brain

Aim. To study the effect of new derivatives of 3 substituted tietan-1,1-dioxide on some mediator systems of the brain in order to determine the possible mechanism of antidepressant effect of these compounds. Methods. In an experiment with male mice studied was the effect of three most active derivatives of tietan-1,1-dioxide, which exhibit antidepressant properties [3 methooxytietan-1,1-dioxide (H14), 3-(2-isopropoxy-5-methylphenoxy)-tietan-1,1-dioxide (H40) and 3-phenylsulphonyltietan-1,1-dioxide (N69)] on the neurotransmitter systems of the brain. In the experiments used were the tests of pharmacological interaction with a sympatholytic reserpine, with a nonselective agonist of dopamine receptors apomorphine, with a dopamine receptor antagonist haloperidol, with a precursor of serotonin 5-oxytryptophan, with a precursor of dopamine levodopa, with an α2-adrenoceptor agonist clonidine, and with an agonist of M-cholinoceptors arecoline. Results. It has been shown that the spectrum of neuropharmacological effects of new derivatives of tietan-1,1-dioxide (H14, H40, N69) is diverse and is associated with the effects on the adrenergic, dopaminergic and serotonergic brain structures. Thus, H14 reduces the severity of hypothermia induced by reserpine, apomorphine, clonidine, and levodopa, as well as the severity of reserpine ptosis, haloperidol catalepsy and 5- oxytryptophan hyperkinesis. H40, in contrast to H14, has no effect on haloperidol catalepsy and hypothermia induced by levodopa, while H69 has no effect on clonidine-induced hypothermia. All the compounds do not alter the latent period and duration of the arecoline tremor. Conclusion. New derivatives of tietan-1,1-dioxide possess properties, which are inherent to antidepressants, and may be recommended for further in-depth study of their antidepressant activity.

scholarly journals Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 656
Author(s):  
Dariusz Koziorowski ◽  
Monika Figura ◽  
Łukasz M. Milanowski ◽  
Stanisław Szlufik ◽  
Piotr Alster ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Protein Gene ◽  
Clinical Presentation ◽  
Neuronal Loss ◽  
Corticobasal Degeneration ◽  
Inflammatory Factors ◽  
Parkinsonian Disorders ◽  
Genetic Features ◽  
The Brain

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

scholarly journals Neuron–Glia Interactions in Tuberous Sclerosis Complex Affect the Synaptic Balance in 2D and Organoid Cultures

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 134
Author(s):  
Stephanie Dooves ◽  
Arianne J. H. van Velthoven ◽  
Linda G. Suciati ◽  
Vivi M. Heine
Keyword(s):  
Tuberous Sclerosis ◽  
Glial Cells ◽  
Tuberous Sclerosis Complex ◽  
Neuronal Development ◽  
Transmembrane Proteins ◽  
Significant Burden ◽  
Epidermal Growth ◽  
And Control ◽  
Egf Signaling ◽  
The Brain

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT+ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals The Brain Resting-State Functional Connectivity Underlying Violence Proneness: Is It a Reliable Marker for Neurocriminology? A Systematic Review

2019 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Ángel Romero-Martínez ◽  
Macarena González ◽  
Marisol Lila ◽  
Enrique Gracia ◽  
Luis Martí-Bonmatí ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Effective Treatment ◽  
Resting State ◽  
Brain Structures ◽  
Prevention Programs ◽  
Angular Gyrus ◽  
Resting State Functional Connectivity ◽  
Treatment And Prevention ◽  
Reliable Marker ◽  
The Brain

Introduction: There is growing scientific interest in understanding the biological mechanisms affecting and/or underlying violent behaviors in order to develop effective treatment and prevention programs. In recent years, neuroscientific research has tried to demonstrate whether the intrinsic activity within the brain at rest in the absence of any external stimulation (resting-state functional connectivity; RSFC) could be employed as a reliable marker for several cognitive abilities and personality traits that are important in behavior regulation, particularly, proneness to violence. Aims: This review aims to highlight the association between the RSFC among specific brain structures and the predisposition to experiencing anger and/or responding to stressful and distressing situations with anger in several populations. Methods: The scientific literature was reviewed following the PRISMA quality criteria for reviews, using the following digital databases: PubMed, PsycINFO, Psicodoc, and Dialnet. Results: The identification of 181 abstracts and retrieval of 34 full texts led to the inclusion of 17 papers. The results described in our study offer a better understanding of the brain networks that might explain the tendency to experience anger. The majority of the studies highlighted that diminished RSFC between the prefrontal cortex and the amygdala might make people prone to reactive violence, but that it is also necessary to contemplate additional cortical (i.e. insula, gyrus [angular, supramarginal, temporal, fusiform, superior, and middle frontal], anterior and posterior cingulated cortex) and subcortical brain structures (i.e. hippocampus, cerebellum, ventral striatum, and nucleus centralis superior) in order to explain a phenomenon as complex as violence. Moreover, we also described the neural pathways that might underlie proactive violence and feelings of revenge, highlighting the RSFC between the OFC, ventral striatal, angular gyrus, mid-occipital cortex, and cerebellum. Conclusions. The results from this synthesis and critical analysis of RSFC findings in several populations offer guidelines for future research and for developing a more accurate model of proneness to violence, in order to create effective treatment and prevention programs.

scholarly journals Glia Not Neurons: Uncovering Brain Dysmaturation in a Rat Model of Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 823
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Tatiana A. Kozlova ◽  
Alena O. Burnyasheva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Brain Structures ◽  
Time Frame ◽  
Oxys Rats ◽  
Unknown Etiology ◽  
Suitable Model ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.

scholarly journals Impact of Fatty Acid-Binding Proteins in α-Synuclein-Induced Mitochondrial Injury in Synucleinopathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 560
Author(s):  
An Cheng ◽  
Wenbin Jia ◽  
Ichiro Kawahata ◽  
Kohji Fukunaga
Keyword(s):  
Fatty Acid ◽  
Binding Proteins ◽  
Neuronal Loss ◽  
Krabbe Disease ◽  
Fatty Acid Binding Proteins ◽  
Mitochondrial Outer Membrane ◽  
Fatty Acid Binding ◽  
Mitochondrial Injury ◽  
Abnormal Accumulation ◽  
The Brain

Synucleinopathies are diverse diseases with motor and cognitive dysfunction due to progressive neuronal loss or demyelination, due to oligodendrocyte loss in the brain. While the etiology of neurodegenerative disorders (NDDs) is likely multifactorial, mitochondrial injury is one of the most vital factors in neuronal loss and oligodendrocyte dysfunction, especially in Parkinson’s disease, dementia with Lewy body, multiple system atrophy, and Krabbe disease. In recent years, the abnormal accumulation of highly neurotoxic α-synuclein in the mitochondrial membrane, which leads to mitochondrial dysfunction, was well studied. Furthermore, fatty acid-binding proteins (FABPs), which are members of a superfamily and are essential in fatty acid trafficking, were reported to trigger α-synuclein oligomerization in neurons and glial cells and to target the mitochondrial outer membrane, thereby causing mitochondrial loss. Here, we provide an updated overview of recent findings on FABP and α-synuclein interactions and mitochondrial injury in NDDs.

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