A5024878629- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Neuropeptides and Animal Physiology
- Dementia and Cognitive Impairment Research
- RNA Research and Splicing
- Stress Responses and Cortisol
- Bacterial Genetics and Biotechnology
- Treatment of Major Depression
- Immune cells in cancer
- Anesthesia and Neurotoxicity Research
- Single-cell and spatial transcriptomics
- Neuroscience and Neuropharmacology Research
- Fungal and yeast genetics research
- Tryptophan and brain disorders
- TGF-β signaling in diseases
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- Bioinformatics and Genomic Networks
- Bipolar Disorder and Treatment
- DNA Repair Mechanisms
- Genetic Associations and Epidemiology
AbbVie (United States)
2021-2024
TKL Research
2016-2017
Lundbeck (United States)
2013-2017
Lundbeck (Germany)
2016
Lundbeck (Denmark)
2005-2015
Max Planck Institute of Psychiatry
2009
Synaptic Research (United States)
1994-2000
University of California, San Francisco
1987
Indiana University Bloomington
1981-1985
Indiana University
1985
The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors, NPFF1 NPFF2, were isolated from human rat tissues. NPFF specifically bound (Kd = 1.13 nm) NPFF2 0.37 nm), both receptors activated by variety of heterologous expression systems. localization mRNA binding sites these the dorsal horn spinal cord, lateral hypothalamus, trigeminal nuclei, thalamic nuclei supports for modulation....
The neuropeptide galanin has been implicated in the regulation of processes such as nociception, cognition, feeding behavior, and hormone secretion. Multiple receptors are predicted to mediate its effects, but only two functionally coupled have reported. We now report cloning a third receptor distinct from GALR1 GALR2. receptor, termed GALR3, was isolated rat hypothalamus cDNA library by both expression homology approaches. GALR3 can encode protein 370 amino acids with 35% 52% identity...
The neuropeptide galanin is widely distributed throughout the central and peripheral nervous systems participates in regulation of processes such as nociception, cognition, feeding behavior, insulin secretion. Multiple receptors are predicted to underlie its physiological effects. We now report isolation by expression cloning a rat receptor cDNA distinct from GALR1. receptor, termed GALR2, was isolated hypothalamus library using a125I-porcine (125I-pGAL) binding assay. GALR2 encoded protein...
Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or of synaptic plasticity genes. Although antidepressants alter these young rodents, their effects older animals are unclear. In mice, we examined the a selective serotonin reuptake inhibitor (fluoxetine) and multimodal antidepressant (vortioxetine) on cognitive affective behaviors, brain gene expression....
Abstract INTRODUCTION Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles APOE ‐linked differences remain unclear. METHODS We performed laser capture microdissection of amyloid beta (Aβ) plaques, 50 μm halo around them, areas distant (> μm) from temporal cortex AD control donors, followed by RNA‐sequencing. RESULTS Aβ exhibited upregulated microglial...
Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer's disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing 628,943 astrocytes from five regions representing stereotypical AD pathology across 32 donors spanning entire normal aging severe continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses AD-vulnerable neural network (spatial axis) or stage...
Splicing of introns from Saccharomyces cerevisiae pre-mRNA requires the conserved sequence TACTAAC; 3'-most A residue is utilized as site branch formation. We showed previously that transcript an actin-HIS4 gene fusion containing mutation TACTAAC to TACTACC (designated C259) spliced inefficiently, thereby preventing growth on histidine precursor histidinol. By selecting for histidinol, we have identified a mutant in which splicing C259 increased fourfold; other mutated not significantly...
Abstract Human microglia are critically involved in Alzheimer’s disease (AD) progression, as shown by genetic and molecular studies. However, their role tau pathology progression human brain has not been well described. Here, we characterized 32 donors along of AD pathology, both time—from early to late pathology—and space—from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal (PFC) visual (V2 V1)—with biochemistry, immunohistochemistry, single nuclei-RNA-sequencing,...
DNA replication of the plasmid ColEl and its relatives is controlled mainly by a small plasmid-encoded transcript known as RNAl.We have studied conformation RNA1 molecules from two related but compatible plasmids, RSF1030, using T1 ribonuclease, Sl nuclease, cobra venom diethyl pyrocarbonate modification probes for secondary structure.Both RNAl contain three double-stranded stems, single-stranded loops, an exposed 5' tail.All loops in both show similar sensitivities to used, do stems 1 3.The...
Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor (GPCR) superfamily and mediate several physiological responses, such as blood pressure, food intake, sedation memory retention. To understand interactions between NPY Y1 subtype its ligands, computer modeling was applied natural peptide agonist, a small molecule antagonist, BIBP3226. An agonist antagonist binding domain elucidated using mutagenesis data for well other GPCR families. The ligands which were investigated...
Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal in vitro models have struggled to recapitulate tau phenomena observed vivo. Here, we aimed define the minimal requirements achieve endogenous aggregation functional neurons utilizing induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical seeded with AD brain-derived competent species or recombinant fibrils displayed increases insoluble,...
RNA1 is a small, plasmid-encoded transcript involved in the replication control of plasmid ColE1. blocks by preventing processing primer RNA necessary for initiation replication. It has been proposed that inhibition involves direct interaction between and RNA. Here we describe an vitro system allows detection characterization RNA1-primer complex. Using this system, have demonstrated association ColE1 results formation X hybrid 5' end Furthermore, analysis mutant molecules containing sequence...
Abstract Alzheimer’s disease (AD) is a common neurodegenerative with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome modulation of in vitro correlates AD features, and used this assess 1525 genes related tau aggregation, autophagy mitochondria. This work revealed (I) network aggregation modulators including NF-κB pathway inflammatory signaling, (II) correlation between mitochondrial...
Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. can be affected by neuroactive medications aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on functions in both pre-clinical clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching spine maturation, elevates hippocampal expression the activity-regulated...
The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states aversive tension dissociation is poorly understood. Our goal was to examine transcriptional changes associated with or within individual patients in a pilot study. Dissociation not only critical symptom BPD but has also been higher risk for self-mutilation depression. We conducted whole blood gene expression profile analysis using quantitative PCR 31 female inpatients BPD. For each...
ABSTRACT Astrocytes play a critical role in brain homeostasis and normal functions but their changes along the spatiotemporal progression of Alzheimer’s disease (AD) neuropathology remain largely unknown. Here we performed single-nucleus RNA-sequencing on regions stereotypical AD pathology from donors ranging entire aging-AD continuum comprising 628,943 astrocyte nuclei 32 across 5 regions. We discovered temporal gene-expression-trajectories with gene sets differentially activated at various...