Cell type-specific activation of p38 MAPK in the brain regions of hypoxic preconditioned mice

2007 ◽  
Vol 51 (8) ◽  
pp. 459-466 ◽  
Author(s):  
Xiangning Bu ◽  
Ping Huang ◽  
Zhifeng Qi ◽  
Nan Zhang ◽  
Song Han ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Brain Regions ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

2018 ◽  
Author(s):  
Jerzy O. Szablowski ◽  
Brian Lue ◽  
Audrey Lee-Gosselin ◽  
Dina Malounda ◽  
Mikhail G. Shapiro
Keyword(s):  
Neural Circuits ◽  
Brain Regions ◽  
Cell Type ◽  
Spatial Targeting ◽  
Temporal Specificity ◽  
Cell Type Specific ◽  
Orally Bioavailable ◽  
G Protein Coupled ◽  
The Brain ◽  
Spatial Cell

ABSTRACTNeurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions of the brain. Existing treatments, including drugs and implantable brain stimulators, aim to modulate the activity of these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach to modulating neural circuits noninvasively with spatial, cell-type and temporal specificity. This approach, called acoustically targeted chemogenetics, or ATAC, uses transient ultrasonic opening of the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded engineered G-protein-coupled receptors, which subsequently respond to systemically administered bio-inert compounds to activate or inhibit the activity of these neurons. We demonstrate this concept in mice by using ATAC to noninvasively modify and subsequently activate or inhibit excitatory neurons within the hippocampus, showing that this enables pharmacological control of memory formation. This technology allows a brief, noninvasive procedure to make one or more specific brain regions capable of being selectively modulated using orally bioavailable compounds, thereby overcoming some of the key limitations of conventional brain therapies.

scholarly journals Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Brain Regions ◽  
Cell Type ◽  
Major Depressive ◽  
Structural Differences ◽  
Neuroimaging Data ◽  
Cell Type Specific

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

scholarly journals Identification of cell-type-specific promoters within the brain using lentiviral vectors

Gene Therapy ◽  
2007 ◽  
Vol 14 (7) ◽  
pp. 575-583 ◽  
Author(s):  
J P Chhatwal ◽  
S E Hammack ◽  
A M Jasnow ◽  
D G Rainnie ◽  
K J Ressler
Keyword(s):  
Lentiviral Vectors ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Neuronal cell-type-specific alternative splicing: A mechanism for specifying connections in the brain?

Neurogenesis ◽  
2015 ◽  
Vol 2 (1) ◽  
pp. e1122699 ◽  
Author(s):  
Joshua Shing Shun Li ◽  
Grace Ji-eun Shin ◽  
S Sean Millard
Keyword(s):  
Alternative Splicing ◽  
Neuronal Cell ◽  
Cell Type ◽  
Specific Alternative ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Using multiple measurements of tissue to estimate subject- and cell-type-specific gene expression

2019 ◽  
Vol 36 (3) ◽  
pp. 782-788 ◽  
Author(s):  
Jiebiao Wang ◽  
Bernie Devlin ◽  
Kathryn Roeder
Keyword(s):  
Gene Expression ◽  
Empirical Bayes ◽  
Brain Regions ◽  
Tissue Level ◽  
Supplementary Information ◽  
Specific Gene ◽  
Expression Data ◽  
Cell Type ◽  
Multiple Measurements ◽  
Cell Type Specific

Abstract Motivation Patterns of gene expression, quantified at the level of tissue or cells, can inform on etiology of disease. There are now rich resources for tissue-level (bulk) gene expression data, which have been collected from thousands of subjects, and resources involving single-cell RNA-sequencing (scRNA-seq) data are expanding rapidly. The latter yields cell type information, although the data can be noisy and typically are derived from a small number of subjects. Results Complementing these approaches, we develop a method to estimate subject- and cell-type-specific (CTS) gene expression from tissue using an empirical Bayes method that borrows information across multiple measurements of the same tissue per subject (e.g. multiple regions of the brain). Analyzing expression data from multiple brain regions from the Genotype-Tissue Expression project (GTEx) reveals CTS expression, which then permits downstream analyses, such as identification of CTS expression Quantitative Trait Loci (eQTL). Availability and implementation We implement this method as an R package MIND, hosted on https://github.com/randel/MIND. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities

Immunity ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 317-333.e6 ◽  
Author(s):  
Xiaoyu Liu ◽  
Daniel P. Nemeth ◽  
Daniel B. McKim ◽  
Ling Zhu ◽  
Damon J. DiSabato ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Restricted Transgene Expression in the Brain with Cell-Type Specific Neuronal Promoters

2012 ◽  
Vol 23 (4) ◽  
pp. 242-254 ◽  
Author(s):  
Aurélie Delzor ◽  
Noelle Dufour ◽  
Fanny Petit ◽  
Martine Guillermier ◽  
Diane Houitte ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Highly efficient and super-bright neurocircuit tracing using vector mixing-based virus cocktail

2019 ◽  
Author(s):  
Pei Sun ◽  
Sen Jin ◽  
Sijue Tao ◽  
Junjun Wang ◽  
Anan Li ◽  
...  
Keyword(s):  
Brain Function ◽  
Individual Cell ◽  
Brain Regions ◽  
Cell Type ◽  
Current Standard ◽  
Functional Studies ◽  
Highly Efficient ◽  
Order Of Magnitude ◽  
Cell Type Specific ◽  
Dependent Vector

ABSTRACTMapping the detailed cell-type-specific input networks and neuronal projectomes are essential to understand brain function in normal and pathological states. However, several properties of current tracing systems, including labeling sensitivity, trans-synaptic efficiencies, reproducibility among different individuals and different Cre-driver animals, still remained unsatisfactory. Here, we developed MAP-ENVIVIDERS, a recombinase system-dependent vector mixing-based strategy for highly efficient neurocircuit tracing. MAP-ENVIVIDERS enhanced tracing efficiency of input networks across the whole brain, with over 10-fold improvement in diverse previously poor-labeled input brain regions and particularly, up to 70-fold enhancement in brainstem compared with the current standard rabies-virus-mediated systems. MAP-ENVIVIDERS was over 10-fold more sensitive for cell-type-specific labeling than previous strategies, enabling us to capture individual cell-type-specific neurons with extremely complex axonal branches and presynaptic axonal boutons, both about one order of magnitude than previously reported and considered. MAP-ENVIVIDERS provides powerful tools for deconstructing novel input/output circuitry towards functional studies and disorders-related mechanisms.

scholarly journals Disease-, region- and cell type specific diversity of α-synuclein carboxy terminal truncations in synucleinopathies

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ethan W. Hass ◽  
Zachary A. Sorrentino ◽  
Yuxing Xia ◽  
Grace M. Lloyd ◽  
John Q. Trojanowski ◽  
...  
Keyword(s):  
Lewy Body Dementia ◽  
Brain Regions ◽  
Motor Nucleus ◽  
Cell Type ◽  
Post Translational Modification ◽  
Cytoplasmic Inclusions ◽  
Specific Distribution ◽  
Cell Type Specific ◽  
Disease Region ◽  
Carboxy Terminal

AbstractSynucleinopathies, including Parkinson’s disease (PD), Lewy body dementia (LBD), Alzheimer’s disease with amygdala restricted Lewy bodies (AD/ALB), and multiple system atrophy (MSA) comprise a spectrum of neurodegenerative disorders characterized by the presence of distinct pathological α-synuclein (αSyn) inclusions. Experimental and pathological studies support the notion that αSyn aggregates contribute to cellular demise and dysfunction with disease progression associated with a prion-like spread of αSyn aggregates via conformational templating. The initiating event(s) and factors that contribute to diverse forms of synucleinopathies remain poorly understood. A major post-translational modification of αSyn associated with pathological inclusions is a diverse array of specific truncations within the carboxy terminal region. While these modifications have been shown experimentally to induce and promote αSyn aggregation, little is known about their disease-, region- and cell type specific distribution. To this end, we generated a series of monoclonal antibodies specific to neo-epitopes in αSyn truncated after residues 103, 115, 119, 122, 125, and 129. Immunocytochemical investigations using these new tools revealed striking differences in the αSyn truncation pattern between different synucleinopathies, brain regions and specific cellular populations. In LBD, neuronal inclusions in the substantia nigra and amygdala were positive for αSyn cleaved after residues 103, 119, 122, and 125, but not 115. In contrast, in the same patients' brain αSyn cleaved at residue 115, as well as 103, 119 and 122 were abundant in the dorsal motor nucleus of the vagus. In patients with AD/ALB, these modifications were only weakly or not detected in amygdala αSyn inclusions. αSyn truncated at residues 103, 115, 119, and 125 was readily present in MSA glial cytoplasmic inclusions, but 122 cleaved αSyn was only weakly or not present. Conversely, MSA neuronal pathology in the pontine nuclei was strongly reactive to the αSyn x-122 neo-epitope but did not display any reactivity for αSyn 103 cleavage. These studies demonstrate significant disease-, region- and cell type specific differences in carboxy terminal αSyn processing associated with pathological inclusions that likely contributes to their distinct strain-like prion properties and promotes the diversity displayed in the degrees of these insidious diseases.

scholarly journals Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain

2021 ◽  
Author(s):  
Sruti Rayaprolu ◽  
Sara Bitarafan ◽  
Ranjita Betarbet ◽  
Sydney N Sunna ◽  
Lihong Cheng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neurological Diseases ◽  
Neuronal Cell ◽  
Cell Types ◽  
Proteomic Profiling ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
The Brain

Isolation and proteomic profiling of brain cell types, particularly neurons, pose several technical challenges which limit our ability to resolve distinct cellular phenotypes in neurological diseases. Therefore, we generated a novel mouse line that enables cell type-specific expression of a biotin ligase, TurboID, via Cre-lox strategy for in vivo proximity-dependent biotinylation of proteins. Using adenoviral-based and transgenic approaches, we show striking protein biotinylation in neuronal cell bodies and axons throughout the mouse brain. We quantified more than 2,000 neuron-derived proteins following enrichment that mapped to numerous subcellular compartments. Synaptic, transmembrane transporters, ion channel subunits, and disease-relevant druggable targets were among the most significantly enriched proteins. Remarkably, we resolved brain region-specific proteomic profiles of Camk2a neurons with distinct functional molecular signatures and disease associations that may underlie regional neuronal vulnerability. Leveraging the neuronal specificity of this in vivo biotinylation strategy, we used an antibody-based approach to uncover regionally unique patterns of neuron-derived signaling phospho-proteins and cytokines, particularly in the cortex and cerebellum. Our work provides a proteomic framework to investigate cell type-specific mechanisms driving physiological and pathological states of the brain as well as complex tissues beyond the brain.

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