scholarly journals Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions

2021 ◽  
Author(s):  
Ryan Gober ◽  
Maryam Ardalan ◽  
Seyedeh Marziyeh Jabbari Shiadeh ◽  
Linda Duque ◽  
Susanna P. Garamszegi ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Brain Regions ◽  
Microglia Activation ◽  
Postmortem Brains

scholarly journals The Emerging Role of the Interplay Among Astrocytes, Microglia, and Neurons in the Hippocampus in Health and Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Daniele Lana ◽  
Filippo Ugolini ◽  
Daniele Nosi ◽  
Gary L. Wenk ◽  
Maria Grazia Giovannini
Keyword(s):  
Acute Inflammation ◽  
Brain Aging ◽  
Morphological Changes ◽  
Brain Regions ◽  
Stratum Radiatum ◽  
Low Grade ◽  
Normal Brain ◽  
Chronic Inflammatory Response ◽  
Health And Disease ◽  
The Brain

For over a century, neurons have been considered the basic functional units of the brain while glia only elements of support. Activation of glia has been long regarded detrimental for survival of neurons but more it appears that this is not the case in all circumstances. In this review, we report and discuss the recent literature on the alterations of astrocytes and microglia during inflammaging, the low-grade, slow, chronic inflammatory response that characterizes normal brain aging, and in acute inflammation. Becoming reactive, astrocytes and microglia undergo transcriptional, functional, and morphological changes that transform them into cells with different properties and functions, such as A1 and A2 astrocytes, and M1 and M2 microglia. This classification of microglia and astrocytes in two different, all-or-none states seems too simplistic, and does not correspond to the diverse variety of phenotypes so far found in the brain. Different interactions occur among the many cell populations of the central nervous system in health and disease conditions. Such interactions give rise to networks of morphological and functional reciprocal reliance and dependency. Alterations affecting one cell population reverberate to the others, favoring or dysregulating their activities. In the last part of this review, we present the modifications of the interplay between neurons and glia in rat models of brain aging and acute inflammation, focusing on the differences between CA1 and CA3 areas of the hippocampus, one of the brain regions most susceptible to different insults. With triple labeling fluorescent immunohistochemistry and confocal microscopy (TIC), it is possible to evaluate and compare quantitatively the morphological and functional alterations of the components of the neuron-astrocyte-microglia triad. In the contiguous and interconnected regions of rat hippocampus, CA1 and CA3 Stratum Radiatum, astrocytes and microglia show a different, finely regulated, and region-specific reactivity, demonstrating that glia responses vary in a significant manner from area to area. It will be of great interest to verify whether these differential reactivities of glia explain the diverse vulnerability of the hippocampal areas to aging or to different damaging insults, and particularly the higher sensitivity of CA1 pyramidal neurons to inflammatory stimuli.

scholarly journals Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

2020 ◽  
Author(s):  
Victor Pando-Naude ◽  
Sebastian Toxto ◽  
Sofia Fernandez-Lozano ◽  
E. Christine Parsons ◽  
Sarael Alcauter ◽  
...  
Keyword(s):  
Systematic Review ◽  
Substance Use ◽  
White Matter ◽  
Substance Use Disorders ◽  
Morphological Changes ◽  
Meta Analysis ◽  
Internal Capsule ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Consumption Pattern

AbstractSubstance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registration CRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.

scholarly journals Alcohol, Aggression, and Violence: From Public Health to Neuroscience

2021 ◽  
Vol 12 ◽  
Author(s):  
Kajol V. Sontate ◽  
Mohammad Rahim Kamaluddin ◽  
Isa Naina Mohamed ◽  
Rashidi Mohamed Pakri Mohamed ◽  
Mohd. Farooq Shaikh ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Mood Disorders ◽  
Emotional Processing ◽  
Morphological Changes ◽  
Brain Regions ◽  
Self Control ◽  
Violent Crimes ◽  
Intoxicated Aggression ◽  
Neurochemical Changes ◽  
And Gender

Alcohol has been associated with violent crimes and domestic violence across many nations. Various etiological factors were linked to chronic alcohol use and violence including psychiatric comorbidities of perpetrators such as personality disorders, mood disorders, and intermittent explosive disorders. Aggression is the precursor of violence and individuals prone to aggressive behaviors are more likely to commit impulsive violent crimes, especially under the influence of alcohol. Findings from brain studies indicate long-term alcohol consumption induced morphological changes in brain regions involved in self-control, decision-making, and emotional processing. In line with this, the inherent dopaminergic and serotonergic anomalies seen in aggressive individuals increase their susceptibility to commit violent crimes when alcohol present in their system. In relation to this, this article intends to investigate the influence of alcohol on aggression with sociopsychological and neuroscientific perspectives by looking into comorbidity of personality or mood disorders, state of the mind during alcohol consumption, types of beverages, environmental trigger, neurochemical changes, and gender differences that influence individual responses to alcohol intake and susceptibility to intoxicated aggression.

ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease

2021 ◽  
Author(s):  
Mitsuru Shinohara ◽  
Junko Hirokawa ◽  
Akemi Shimodaira ◽  
Yoshitaka Tashiro ◽  
Kaoru Suzuki ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Brain Regions ◽  
Insoluble Fraction ◽  
The Other ◽  
Disease Stage ◽  
Brain Areas ◽  
Postmortem Brains ◽  
Biochemical Level ◽  
The Brain ◽  
Control Samples

Abstract Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

FKN/CX3CR1 Axis Facilitated Migraine-like Behaviors via Activating Thalamic-cortical Network Microglia in SE Rat Models

2021 ◽  
Author(s):  
Yanjie Zhou ◽  
Lily Zhang ◽  
Yuyan Hao ◽  
Liu Yang ◽  
Zheman Xiao
Keyword(s):  
Microglial Activation ◽  
Neural Circuit ◽  
Signal Transmission ◽  
Brain Regions ◽  
Microglia Activation ◽  
Rat Models ◽  
Inflammatory Soup ◽  
Bv2 Microglia ◽  
Neuronal Signal ◽  
Patients With Epilepsy

Abstract Background: The incidence of migraines is higher among people with epilepsy than healthy people, and these two common diseases are proposed to have some shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglia activation is crucial for abnormal neuronal signal transmission. However, whether and how microglia are activated, and their role in comorbidities after activation remains unclear. This study aimed to explore the characteristics and mechanism of microglia activation after seizures and its effect on migraine.Methods: Status epilepticus (SE) rat models induced by lithium chloride (LiCl)-pilocarpine intraperitoneal injection and migraine rat models induced by repeated inflammatory soup (IS) dural injections were generated and assessed for molecular and histopathologic evidence of microglial activation target of fractalkine (FKN) signaling. HT22-BV2 transwell coculture was used to explore the interaction between neurons and microglia. LPS (a microglia agonist) and FKN stimulation of BV2 microglia cells were used to evaluate changes in BDNF content after microglia activation.Results: Microglia were specifically hyperplasia and activation in the cortical-thalamus-sp5c neural circuit, which were pain-related brain regions, accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Meanwhile, SE-induced increased nociceptive behavior and the FKN/CX3CR1 axis in migraine rat models. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglia activation in migraine rat models after seizures, while FKN infusion in migraine rat models exacerbated hyperalgesia and microglia activation associated with BDNF-Trkb signaling. Furthermore, in neuron-BV2 coculture, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased. Activating microglia with LPS and FKN stimulation increased BDNF synthesis in BV2 microglia.Conclusions: Our results indicated that epilepsy facilitated migraine through the cortical-thalamus-sp5c microglia activated and interactions with neurons by the FKN/CX3CR1 axis, resulting in BDNF release. Blocking the FKN/CX3CR1 axis and microglia activation are potential therapeutic targets for preventing and treating migraine in patients with epilepsy.

scholarly journals Morphological Neuroimaging Biomarkers for Tinnitus: Evidence Obtained by Applying Machine Learning

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Yawen Liu ◽  
Haijun Niu ◽  
Jianming Zhu ◽  
Pengfei Zhao ◽  
Hongxia Yin ◽  
...  
Keyword(s):  
Machine Learning ◽  
Healthy Subjects ◽  
Morphological Changes ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Classification Model ◽  
Middle Temporal Gyrus ◽  
Support Vector ◽  
Svm Classifier ◽  
Neuroimaging Biomarkers

According to previous studies, many neuroanatomical alterations have been detected in patients with tinnitus. However, the results of these studies have been inconsistent. The objective of this study was to explore the cortical/subcortical morphological neuroimaging biomarkers that may characterize idiopathic tinnitus using machine learning methods. Forty-six patients with idiopathic tinnitus and fifty-six healthy subjects were included in this study. For each subject, the gray matter volume of 61 brain regions was extracted as an original feature pool. From this feature pool, a hybrid feature selection algorithm combining the F-score and sequential forward floating selection (SFFS) methods was performed to select features. Then, the selected features were used to train a support vector machine (SVM) model. The area under the curve (AUC) and accuracy were used to assess the performance of the classification model. As a result, a combination of 13 cortical/subcortical brain regions was found to have the highest classification accuracy for effectively differentiating patients with tinnitus from healthy subjects. These brain regions include the bilateral hypothalamus, right insula, bilateral superior temporal gyrus, left rostral middle frontal gyrus, bilateral inferior temporal gyrus, right inferior parietal lobule, right transverse temporal gyrus, right middle temporal gyrus, right cingulate gyrus, and left superior frontal gyrus. The accuracy in the training and test datasets was 80.49% and 80.00%, respectively, and the AUC was 0.8586. To the best of our knowledge, this is the first study to elucidate brain morphological changes in patients with tinnitus by applying an SVM classifier. This study provides validated cortical/subcortical morphological neuroimaging biomarkers to differentiate patients with tinnitus from healthy subjects and contributes to the understanding of neuroanatomical alterations in patients with tinnitus.

scholarly journals Morphological Biomarker Differentiating MCI Converters from Nonconverters: Longitudinal Evidence Based on Hemispheric Asymmetry

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaojing Long ◽  
Chunxiang Jiang ◽  
Lijuan Zhang
Keyword(s):  
Medial Temporal Lobe ◽  
Hemispheric Asymmetry ◽  
Morphological Changes ◽  
Brain Regions ◽  
Thickness Measurement ◽  
Morphological Variations ◽  
Asymmetry Analysis ◽  
Potential Index ◽  
Longitudinal Mri ◽  
Magnetic Resonance Imaging Mri

Identifying subjects with mild cognitive impairment (MCI) who may probably progress to Alzheimer’s disease (AD) is important for better understanding the disease mechanisms and facilitating early treatments. In addition to the direct volumetric and thickness measurement based on high-resolution magnetic resonance imaging (MRI), hemispheric asymmetry could be a potential index to detect morphological variations in MCI patients with a high risk of conversion to AD. The present study collected a set of longitudinal MRI data from 53 MCI converters and nonconverters and investigated the asymmetry differences between groups. Asymmetry variation was observed in the medial temporal lobe, especially in the entorhinal cortex, between converters and nonconverters 3 years before the former developed AD. The proposed asymmetry analysis was observed to be sensitive to detect morphological changes between groups as compared to the methods of voxel-based morphometry (VBM) and thickness measurement. Hemispheric asymmetry in specific brain regions as a neuroimaging biomarker can provide helpful information for prediction of MCI conversion.

scholarly journals Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Milo Grotell ◽  
Bjørnar den Hollander ◽  
Aaro Jalkanen ◽  
Essi Törrönen ◽  
Jouni Ihalainen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Morphological Changes ◽  
Brain Regions ◽  
Long Term Effects ◽  
Brain Scans ◽  
Ambient Temperatures ◽  
Delayed Effects ◽  
Golgi Staining ◽  
Adolescent Rats

Mephedrone (4-MMC), despite its illegal status, is still a widely used psychoactive substance. Its effects closely mimic those of the classical stimulant drug methamphetamine (METH). Recent research suggests that unlike METH, 4-MMC is not neurotoxic on its own. However, the neurotoxic effects of 4-MMC may be precipitated under certain circumstances, such as administration at high ambient temperatures. Common use of 4-MMC in conjunction with alcohol raises the question whether this co-consumption could also precipitate neurotoxicity. A total of six groups of adolescent rats were treated twice daily for four consecutive days with vehicle, METH (5 mg/kg) or 4-MMC (30 mg/kg), with or without ethanol (1.5 g/kg). To investigate persistent delayed effects of the administrations at two weeks after the final treatments, manganese-enhanced magnetic resonance imaging brain scans were performed. Following the scans, brains were collected for Golgi staining and spine analysis. 4-MMC alone had only subtle effects on neuronal activity. When administered with ethanol, it produced a widespread pattern of deactivation, similar to what was seen with METH-treated rats. These effects were most profound in brain regions which are known to have high dopamine and serotonin activities including hippocampus, nucleus accumbens and caudate-putamen. In the regions showing the strongest activation changes, no morphological changes were observed in spine analysis. By itself 4-MMC showed few long-term effects. However, when co-administered with ethanol, the apparent functional adaptations were profound and comparable to those of neurotoxic METH.

Integrating high-throughput genetics and neuroimaging technologies promises greater information on neurobiological anomalies in neurodegenerative diseases

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
High Throughput ◽  
Morphological Changes ◽  
Brain Area ◽  
Temporal Distribution ◽  
Brain Regions ◽  
Brain Morphology ◽  
Expression Data ◽  
Imaging Research

The integration of high-throughput genomics and neuroimaging technology has the promise of providing more information about neurobiological irregularities in neurodegenerative illnesses. Transcriptomics-derived connections provide insight into the molecular trajectory of neurodegeneration, prioritizing particular systems and networks while also considering other aspects, including neuropathology and cognition. Causal links between gene expression and brain morphology are unknown, however. If omics systems have a wide impact upstream, they can influence morphological changes identified by MRI. Gene expression is a signal indicating a process already underway in a diseased brain area if it is downstream of structural brain changes. More study on people in the early stages of disease may give insights into the temporal connection between anatomical and expression problems.One such thought is molecular stereotactic propagation. Changes in gene expression may travel across the brain, according to this notion, through tractography trails. They follow the successive pattern of afflicted regions and the temporal distribution of sensitive locations. In addition, cell motility genes are often overexpressed in vulnerable locations. On the other hand, the data on gene expression and its relevance to structural change propagation is still conflicting. The role of immunological processes and motility-related genes in neurodegeneration appears to be validated by expression data.There are no therapies available for neurodegenerative diseases. Symptom development and diagnosis is often delayed due to advanced MRI and clinical stages. Early diagnosis is crucial since therapy interventions should ideally aim at commencing pathogenic processes as soon as possible to avoid the onset of disease and restrict the course of disease. This requires dependable neurodegenerative biomarkers with diagnostic validity. Unfortunately, transcriptomics still has several important limitations. There is a paucity of high-quality expression data encompassing a large number of brain regions, expression data generally collected from healthy persons, comparisons with neuroimaging data from degenerative cohorts, and a lack of consistent approach for transcriptional imaging research. By overcoming this barrier, researchers can uncover prodromal stages of neurodegeneration and therapeutic molecular targets.

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