A5049357772- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Pluripotent Stem Cells Research
- Nicotinic Acetylcholine Receptors Study
- Anesthesia and Neurotoxicity Research
- Graphene and Nanomaterials Applications
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Medicinal Plants and Neuroprotection
- Genetic Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Nanoparticles: synthesis and applications
- Neuroscience and Neural Engineering
- Fullerene Chemistry and Applications
- Alzheimer's disease research and treatments
- Lysosomal Storage Disorders Research
- S100 Proteins and Annexins
- Adenosine and Purinergic Signaling
- Neurogenesis and neuroplasticity mechanisms
- Single-cell and spatial transcriptomics
- RNA and protein synthesis mechanisms
Icahn School of Medicine at Mount Sinai
2020-2024
Allen Institute for Brain Science
2021-2024
Research Network (United States)
2022-2024
Mount Sinai Hospital
2021-2023
New York Stem Cell Foundation
2021-2023
Universidade Federal do Rio Grande
2011-2022
University of Toronto
2017-2022
University of Rio Grande and Rio Grande Community College
2022
Robarts Clinical Trials
2016
Western University
2016
Abstract Accumulation of advanced glycation end products (AGEs) on biopolymers accompanies cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development early onset Parkinson’s Disease (PD) caused by loss-of-function DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, find that lysosomal proteolysis is impaired, causing accumulate, α-synuclein (α-syn)...
Significance Huntington’s disease (HD) is a fatal neurodegenerative disorder that currently has no cure. Although HD classically considered motor disorder, patients experience learning and memory deficits years before the onset of symptoms, these resemble those observed in mouse models. In this work, using transgenic models HD, we demonstrate action neurotransmitter GABA switched from inhibitory to excitatory. By treating mice with clinically used diuretic (bumetanide), which restores GABA,...
Abstract Cholecystokinin-expressing GABAergic (CCK-GABA) neurons are perisomatic inhibitory cells that have been argued to regulate emotion and sculpt the network oscillations associated with cognition. However, no study has selectively manipulated CCK-GABA neuron activity during behavior in freely-moving animals. To explore behavioral effects of activating on cognition, we utilized a novel intersectional genetic mouse model coupled chemogenetic approach. Specifically, generated triple...
Parkinson's disease (PD) is a complex and highly variable neurodegenerative disease. Familial PD caused by mutations in several genes with diverse mostly unknown functions. It unclear how dysregulation of these results the relatively selective death nigral dopaminergic neurons (DNs). To address this question, we modeled knocking out PARKIN (PRKN), DJ-1 (PARK7), ATP13A2 (PARK9) independent isogenic human pluripotent stem cell (hPSC) lines. We found increased levels oxidative stress all...
Preys use their memory – where they sensed a predatory threat and whether safe shelter is nearby to dynamically control survival instinct avoid harm reach safety. However, it remains unknown which brain regions are involved, how such top-down of innate behavior implemented at the circuit level. Here, using adult male mice, we show that anterior hypothalamic nucleus (AHN) best positioned this task as an exclusive target hippocampus (HPC) within medial defense system. Selective optogenetic...
Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), protein required for release. We measured long-term potentiation Schaffer collateral-CA1 synapses vivo assessed using mouse touchscreen version paired associates learning task (PAL). Acquisition PAL...
Memory persistence needs a new event of consolidation 12 h after the acquisition. We investigated role cholinergic activity on memory. For this purpose, we performed treatments 9 or acquisition and memory tested 2 7 days inhibitory avoidance (IA) training. Here report that medial septum, by transitorily inactivating structure with lidocaine IA training, is essential for at 7th day, but not formation 2nd day. also muscarinic nicotinic receptors CA1 area are engaged persistence. Since...
Cholinergic vulnerability, characterized by loss of acetylcholine (ACh), is one the hallmarks Alzheimer9s disease (AD). Previous work has suggested that decreased ACh activity in AD may contribute to pathological changes through global alterations alternative splicing. This occurs, at least partially, via regulation expression a critical protein family RNA processing, heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins. These proteins regulate several steps metabolism, including...
The hypothalamus is a region of the brain that plays an important role in regulating body functions and behaviors. There growing interest human pluripotent stem cells (hPSCs) for modeling diseases affect hypothalamus. Here, we established hPSC-derived organoid differentiation protocol to model cellular diversity this region. Using hPSC line with tyrosine hydroxylase (TH)-TdTomato reporter dopaminergic neurons (DNs) other TH-expressing cells, interrogated DN-specific pathways...
Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized polyethylene glycol (SWNT-PEG). For this purpose, analyzed biochemical, histological, behavioral biodistribution parameters understand how material behaves in vitro vivo using fish Danio rerio (zebrafish) as a model. The results for brain homogenates indicated that SWNT-PEG had an...
Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, ability these to cross cell membranes interact with neural cells brings need assessment their potential adverse effects on nervous system. This study aimed investigate biopersistence single-walled carbon functionalized polyethylene glycol (SWCNT-PEG) directly infused into rat hippocampus. Contextual fear conditioning, Y-maze open field tasks were performed evaluate SWCNT-PEG memory...
Memory persistence in the inhibitory avoidance (IA) task has been recently shown to require a new event of consolidation 12 hr after acquisition.The immobilization stress (IS) model is largely used study effects on memory.In this we investigated interactions between by and its effect memory, also possible mediated -adrenergic modulation memory persistence.An enhancement long-term (LTM) caused through applied IA training was observed when animals were submitted 15 min or 1 IS, but not 3...
Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate neurotoxicity these nanomaterials. The present work assessed effects single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on consolidation and retrieval contextual fear memory rats oxidative stress parameters hippocampus. SWCNT-PEG were dispersed water at concentrations 0.5, 1.0, 2.1 mg/mL infused into rat infusion was...
Here, we describe a high-throughput 3D differentiation protocol for deriving midbrain dopaminergic neurons from human pluripotent stem cells. The use of organoids has become prevalent in disease modeling, but there is high demand more homogeneous cultures. Our approach advantageous large-scale production uniform that can be maintained diverse formats, and our reporters allow sorting neurons. maturing long-term organoid cultures used as model the entire midbrain. For complete details on...
Abstract Background The accumulation of abnormal tau protein in neurons and glia the human brain is defining feature neurodegenerative diseases known as tauopathies. Progressive supranuclear palsy (PSP), most common primary tauopathy, typified by selective vulnerability dopaminergic midbrain leading to an atypical parkinsonian movement disorder. To investigate candidate disease mechanisms underlying PSP, there a critical need for model systems that more accurately recapitulate cellular...
ABSTRACT Background ATP10B, a transmembrane lipid flippase located in late endosomes and lysosomes, facilitates the export of glucosylceramide phosphatidylcholine by coupling this process to ATP hydrolysis. Recently, loss-of-function mutations ATP10B gene have been identified Parkinson’s disease patients, pointing as candidate genetic risk factor. Previous studies shown compromised lysosomal functionality upon knockdown human cell lines primary cortical neurons. However, its role vivo...
Abstract Background Progressive supranuclear palsy (PSP) is the most common primary tauopathy, with a constellation of pathological features including 4R‐tau positive neurofibrillary tangles and tufted astrocytes. Most PSP cases are sporadic associated structural variation in 17q21.31 MAPT locus as well other loci, EIF2AK3 which critical for integrated stress response (ISR). Despite these known genetic risk associations, mechanisms underlying disease pathogenesis unclear. To investigate...