Synaptic proteins after electroconvulsive stimulation: Reversibility and regional differences in the brain

A major challenge in neuroscience is how to study structural alterations in the brain. Even small changes in synaptic composition could have severe outcomes for body functions. Many neuropathological diseases are attributable to disorganization of particular synaptic proteins. Yet, to detect and comprehensively describe and evaluate such often rather subtle deviations from the normal physiological status in a detailed and quantitative manner is very challenging. Here, we have compared side-by-side several commercially available light microscopes for their suitability in visualizing synaptic components in larger parts of the brain at low resolution, at extended resolution as well as at super-resolution. Microscopic technologies included stereo, widefield, deconvolution, confocal, and super-resolution set-ups. We also analyzed the impact of adaptive optics, a motorized objective correction collar and CUDA graphics card technology on imaging quality and acquisition speed. Our observations evaluate a basic set of techniques, which allow for multi-color brain imaging from centimeter to nanometer scales. The comparative multi-modal strategy we established can be used as a guide for researchers to select the most appropriate light microscopy method in addressing specific questions in brain research, and we also give insights into recent developments such as optical aberration corrections.

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Neuropathology does not Correlate with Regional Differences in the Extent of Expansion of CTG Repeats in the Brain with Myotonic Dystrophy Type 1

ACTA HISTOCHEMICA ET CYTOCHEMICA ◽

10.1267/ahc.10019 ◽

2010 ◽

Vol 43 (6) ◽

pp. 149-156 ◽

Cited By ~ 33

Author(s):

Kyoko Itoh ◽

Maki Mitani ◽

Kunihiko Kawamoto ◽

Naonobu Futamura ◽

Itaru Funakawa ◽

...

Keyword(s):

Myotonic Dystrophy ◽

Regional Differences ◽

Myotonic Dystrophy Type 1 ◽

Myotonic Dystrophy Type ◽

Ctg Repeats ◽

The Brain

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Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology

Scientific Reports ◽

10.1038/srep30069 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 8

Author(s):

Felipe J. Bodaleo ◽

Carolina Montenegro-Venegas ◽

Daniel R. Henríquez ◽

Felipe A. Court ◽

Christian Gonzalez-Billault

Keyword(s):

Axonal Guidance ◽

Synaptic Proteins ◽

Glutamatergic Synapses ◽

Presynaptic Terminals ◽

Synaptic Contacts ◽

Mature Neurons ◽

Release Assay ◽

Synaptic Vesicle Fusion ◽

The Brain

Abstract Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro.

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Developmental and seizure-related regional differences in immediate early gene expression and GABAergic abnormalities in the brain of EL mice

Epilepsy Research ◽

10.1016/s0920-1211(96)00034-4 ◽

1996 ◽

Vol 26 (1) ◽

pp. 3-14 ◽

Cited By ~ 21

Author(s):

Yoshiya L. Murashima ◽

Kimihiro Kasamo ◽

Jiro Suzuki

Keyword(s):

Gene Expression ◽

Regional Differences ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Early Gene Expression ◽

El Mice ◽

The Brain

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Microglia and Synapse: Interactions in Health and Neurodegeneration

Neural Plasticity ◽

10.1155/2013/425845 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 42

Author(s):

Zuzana Šišková ◽

Marie-Ève Tremblay

Keyword(s):

Neurodegenerative Diseases ◽

Dendritic Spines ◽

Microglial Cell ◽

Immune Defense ◽

Synaptic Proteins ◽

Neuronal Function ◽

Dynamic Interactions ◽

Main Form ◽

The Brain ◽

Neuronal Compartments

A series of discoveries spanning for the last few years has challenged our view of microglial function, the main form of immune defense in the brain. The surveillance of neuronal circuits executed by each microglial cell overseeing its territory occurs in the form of regular, dynamic interactions. Microglial contacts with individual neuronal compartments, such as dendritic spines and axonal terminals, ensure that redundant or dysfunctional elements are recognized and eliminated from the brain. Microglia take on a new shape that is large and amoeboid when a threat to brain integrity is detected. In this defensive form, they migrate to the endangered sites, where they help to minimize the extent of the brain insult. However, in neurodegenerative diseases that are associated with misfolding and aggregation of synaptic proteins, these vital defensive functions appear to be compromised. Many microglial functions, such as phagocytosis, might be overwhelmed during exposure to the abnormal levels of misfolded proteins in their proximity. This might prevent them from attending to their normal duties, such as the stripping of degenerating synaptic terminals, before neuronal function is irreparably impaired. In these conditions microglia become chronically activated and appear to take on new, destructive roles by direct or indirect inflammatory attack.

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The Use of Proteomics in Biomarker Discovery in Neurodegenerative Diseases

Disease Markers ◽

10.1155/2005/848676 ◽

2005 ◽

Vol 21 (2) ◽

pp. 81-92 ◽

Cited By ~ 60

Author(s):

Pia Davidsson ◽

Magnus Sjögren

Keyword(s):

Neurodegenerative Diseases ◽

Biomarker Discovery ◽

Neurological Diseases ◽

Synaptic Proteins ◽

Clinical Proteomics ◽

Protein Patterns ◽

Differential Protein ◽

Csf Proteins ◽

New Biomarkers ◽

The Brain

Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein,β-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of bothβ-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-β-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.

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Effects of RORγt overexpression on the murine central nervous system

10.21203/rs.3.rs-23233/v1 ◽

2020 ◽

Author(s):

Tetsuya Sasaki ◽

Rei Nagata ◽

Satoru Takahashi ◽

Yosuke Takei

Keyword(s):

Dentate Gyrus ◽

Th17 Cells ◽

Wild Type Mouse ◽

Synaptic Proteins ◽

Test Results ◽

Wild Type ◽

T Helper 17 ◽

Continuous Increase ◽

Subtle Effect ◽

The Brain

Abstract Objective T-helper 17 (Th17) cells are a subset of CD4 + T cells that produce interleukin (IL)-17A. Recent studies showed that an increase in circulating IL-17A causes cognitive dysfunction, although it is unknown how increased systemic IL-17A affects brain function. Using transgenic mice overexpressing RORγt, a transcription factor essential for differentiation of Th17 cells (RORγt Tg mice), we examined changes in the brain caused by chronically increased IL-17A resulting from excessive activation of Th17 cells. Results RORγt Tg mice exhibited elevated Rorc and IL-17A mRNA expression in the colon, as well as a chronic increase in circulating IL-17A. We found that the immunoreactivity of Iba1 and density of microglia were lower in the dentate gyrus of RORγt Tg mice compared with wild-type mice. However, GFAP + astrocytes were unchanged in the hippocampi of RORγt Tg mice. Levels of synaptic proteins were not significantly different between RORγt Tg and wild-type mouse brains. In addition, novel object location test results indicated no difference in preference between these mice. Our findings indicate that a continuous increase of IL-17A in response to RORγt overexpression resulted in decreased microglia activity in the dentate gyrus, but had only a subtle effect on murine hippocampal functions.

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