Study of pre-synaptic internalisation in human schizophrenia brains

AbstractAimsEfficient synaptic communication is crucial to maintain healthy behavioural and cognitive processes. Individuals affected by schizophrenia present behavioural symptoms and alterations in decision-making, suggesting altered synaptic integrity as the support of the illness. It is currently unknown how this synaptic change is mediated in schizophrenia, but microglia have been proposed to act as the culprit, actively removing synapses pathologically. Here, we aimed to explore the interaction between microglia and synaptic uptake in human post-mortem tissue.MethodsWe assessed microglial activation and synaptic internalisation by microglia in a post-mortem human tissue of 10 control and 10 schizophrenia cases. Immunohistochemistry was performed to identify microglia (Iba1 and CD68) and the presynaptic terminals (synapsin I).ResultsWe found no difference in microglial expression, nor a difference in pre-synaptic protein level phagocyted by microglia between the two groups.ConclusionsOur findings are consistent with the brain imaging studies in schizophrenia implying that microglia play a role mainly during the early phases of the disease, by example in active synapse remodelling, which is not detected in the chronic stage of the illness.

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Vorläufige Ergebnisse von 99mTc-HMPAO-SPECT-Untersuchungen bei endogenen Psychosen

Nuklearmedizin ◽

10.1055/s-0038-1629475 ◽

1989 ◽

Vol 28 (03) ◽

pp. 88-91

Author(s):

J. Schröder ◽

H. Henningsen ◽

H. Sauer ◽

P. Georgi ◽

K.-R. Wilhelm

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Regional Cerebral Blood Flow ◽

Regions Of Interest ◽

Post Mortem ◽

Regional Cerebral Blood ◽

Hmpao Spect ◽

Endogenous Psychoses ◽

The Brain ◽

99Mtc Hmpao

18 psychopharmacologically treated patients (7 schizophrenics, 5 schizoaffectives, 6 depressives) were studied using 99mTc-HMPAO-SPECT of the brain. The regional cerebral blood flow was measured in three transversal sections (infra-/supraventricular, ventricular) within 6 regions of interest (ROI) respectively (one frontal, one parietal and one occipital in each hemisphere). Corresponding ROIs of the same section in each hemisphere were compared. In the schizophrenics there was a significantly reduced perfusion in the left frontal region of the infraventricular and ventricular section (p < 0.02) compared with the data of the depressives. The schizoaffectives took an intermediate place. Since the patients were treated with psychopharmaca, the result must be interpreted cautiously. However, our findings seem to be in accordance with post-mortem-, CT- and PET-studies presented in the literature. Our results suggest that 99mTc-HMPAO-SPECT may be helpful in finding cerebral abnormalities in endogenous psychoses.

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PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats

Translational Psychiatry ◽

10.1038/s41398-020-01155-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu Liu ◽

Lizhen Wang ◽

Donghui Pan ◽

Mingzhu Li ◽

Yaoqi Li ◽

...

Keyword(s):

Microglial Activation ◽

Light Therapy ◽

Emission Tomography ◽

Noninvasive Evaluation ◽

Mild Stress ◽

Positron Emission ◽

Therapeutic Choice ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

The Brain

AbstractLight therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [18F]DPA-714 and [18F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to normal rats (p < 0.05) and the depressive-like behavior could be ameliorated by light therapy. Besides, depressive rats had significantly higher [18F]DPA-714 uptake and lower [18F]FDG uptake compare to normal rats in 11 and 9 regions of interest (ROIs) of the brain, respectively (p < 0.05). After 5 weeks of light therapy, higher [18F]FDG and [18F]exendin-4 uptake was observed in most ROIs of light therapy-treated depressive rats compared to untreated depressive rats (p < 0.05) and no significant differences existed in [18F]DPA-714 uptake between the two groups. This study demonstrated that light therapy can ameliorate depressive-like behavior, improve glucose metabolism, and halt the decline of brain GLP-1R expression of depressive rats, but have no effects on microglial activation caused by CUMS. Besides, this study validated that [18F]DPA-714 and [18F]exendin-4 PET have the potential for noninvasive evaluation of microglial activation and GLP-1R expression in the brain of depression.

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Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain

Science Translational Medicine ◽

10.1126/scitranslmed.aan0237 ◽

2018 ◽

Vol 10 (471) ◽

pp. eaan0237 ◽

Cited By ~ 29

Author(s):

Diego F. Niño ◽

Qinjie Zhou ◽

Yukihiro Yamaguchi ◽

Laura Y. Martin ◽

Sanxia Wang ◽

...

Keyword(s):

Necrotizing Enterocolitis ◽

Microglial Activation ◽

Gastrointestinal Disease ◽

Cognitive Impairments ◽

High Mobility ◽

Neurological Dysfunction ◽

Mucosal Inflammation ◽

Signaling Axis ◽

The Brain

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.

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Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

Journal of Neuroinflammation ◽

10.1186/s12974-020-02054-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Song Cao ◽

Daniel W. Fisher ◽

Guadalupe Rodriguez ◽

Tian Yu ◽

Hongxin Dong

Keyword(s):

Spinal Cord ◽

Locus Coeruleus ◽

Microglial Activation ◽

Healthy Aging ◽

Cell Types ◽

Norepinephrine System ◽

Protective Processes ◽

The Central Nervous System ◽

Brain And Spinal Cord ◽

The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

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Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging

Multiple Sclerosis Journal ◽

10.1177/1352458508096876 ◽

2008 ◽

Vol 15 (2) ◽

pp. 180-188 ◽

Cited By ~ 49

Author(s):

CP Gilmore ◽

JJG Geurts ◽

N Evangelou ◽

JCJ Bot ◽

RA van Schijndel ◽

...

Keyword(s):

Spinal Cord ◽

White Matter ◽

Mr Imaging ◽

High Field ◽

Grey Matter ◽

Great Majority ◽

Proton Density ◽

Post Mortem ◽

Mr Images ◽

The Brain

Background Post-mortem studies demonstrate extensive grey matter demyelination in MS, both in the brain and in the spinal cord. However the clinical significance of these plaques is unclear, largely because they are grossly underestimated by MR imaging at conventional field strengths. Indeed post-mortem MR studies suggest the great majority of lesions in the cerebral cortex go undetected, even when performed at high field. Similar studies have not been performed using post-mortem spinal cord material. Aim To assess the sensitivity of high field post-mortem MRI for detecting grey matter lesions in the spinal cord in MS. Methods Autopsy material was obtained from 11 MS cases and 2 controls. Proton Density-weighted images of this formalin-fixed material were acquired at 4.7Tesla before the tissue was sectioned and stained for Myelin Basic Protein. Both the tissue sections and the MR images were scored for grey matter and white matter plaques, with the readers of the MR images being blinded to the histopathology results. Results Our results indicate that post-mortem imaging at 4.7Tesla is highly sensitive for cord lesions, detecting 87% of white matter lesions and 73% of grey matter lesions. The MR changes were highly specific for demyelination, with all lesions scored on MRI corresponding to areas of demyelination. Conclusion Our work suggests that spinal cord grey matter lesions may be detected on MRI more readily than GM lesions in the brain, making the cord a promising site to study the functional consequences of grey matter demyelination in MS.

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Priors and Prejudice: How prior knowledge shapes intergroup perception

10.31234/osf.io/3tyrg ◽

2021 ◽

Author(s):

Hugh McGovern ◽

Marte Otten

Keyword(s):

Social Psychology ◽

Prior Knowledge ◽

Cognitive Processes ◽

Social Neuroscience ◽

Intergroup Bias ◽

Predictive Processing ◽

Future Research ◽

Intergroup Perception ◽

The Brain ◽

Processing Framework

Bayesian processing has become a popular framework by which to understand cognitive processes. However, relatively little has been done to understand how Bayesian processing in the brain can be applied to understanding intergroup cognition. We assess how categorization and evaluation processes unfold based on priors about the ethnic outgroup being perceived. We then consider how the precision of prior knowledge about groups differentially influence perception depending on how the information about that group was learned affects the way in which it is recalled. Finally, we evaluate the mechanisms of how humans learn information about other ethnic groups and assess how the method of learning influences future intergroup perception. We suggest that a predictive processing framework for assessing prejudice could help accounting for seemingly disparate findings on intergroup bias from social neuroscience, social psychology, and evolutionary psychology. Such an integration has important implications for future research on prejudice at the interpersonal, intergroup, and societal levels.

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Lantern Demonstration of Gross Lesions of the Cerebrum

Journal of Mental Science ◽

10.1192/bjp.47.199.729 ◽

1901 ◽

Vol 47 (199) ◽

pp. 729-737 ◽

Cited By ~ 2

Author(s):

Joseph Shaw Bolton

Keyword(s):

Cerebral Cortex ◽

Dura Mater ◽

Royal Society ◽

Mental Disease ◽

Post Mortem ◽

Pyramidal Layer ◽

Gross Lesions ◽

The Subject ◽

The Brain ◽

Morbid Conditions

This demonstration was a further report on the subject laid before the Association at the meeting at Claybury in February last, viz., the morbid changes occurring in the brain and other intra-cranial contents in amentia and dementia. In a paper read before the Royal Society in the spring of 1900, and subsequently published in the Philosophical Transactions, it was stated, as the result of a systematic micrometric examination of the visuo-sensory (primary visual) and visuo-psychic (lower associational) regions of the cerebral cortex, that the depth of the pyramidal layer of nerve-cells varies with the amentia or dementia existing in the patient. At the meeting of the Association referred to it was further shown, from an analysis, clinical and pathological, of 121 cases of insanity which appeared consecutively in the post-mortem room at Claybury, that the morbid conditions inside the skull-cap in insanity, viz., abnormalities in the dura mater, the pia arachnoid, the ependyma and intra-cranial fluid, etc., are the accompaniments of and vary in degree with dementia alone, and are independent of the duration of the mental disease. Since that date the pre-frontal (higher associational) region has been systematically examined in nineteen cases, viz., normal persons and normal aments (infants), and cases of amentia, of chronic and recurrent insanity without appreciable dementia, and of dementia, and the results obtained form the subject of the present demonstration. A paper on the whole subject will shortly be published in the Archives of the Claybury Laboratory.

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