A5034280470- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Parkinson's Disease Mechanisms and Treatments
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- S100 Proteins and Annexins
- Nerve injury and regeneration
- Analytical Methods in Pharmaceuticals
- Pharmaceutical studies and practices
- Telomeres, Telomerase, and Senescence
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Cholinesterase and Neurodegenerative Diseases
- CAR-T cell therapy research
- Cancer and biochemical research
- Cellular Mechanics and Interactions
- Hormonal and reproductive studies
- Health Systems, Economic Evaluations, Quality of Life
University of Minnesota
2020-2025
University of Minnesota System
2022-2024
Weatherford College
2024
Instituto Cajal
2023
Twin Cities Orthopedics
2023
University of Minnesota Medical Center
2019-2022
Universidad Autónoma de Madrid
2011-2018
Hospital Universitario de La Princesa
2018
University of Castilla-La Mancha
2018
Parkinson's disease dementia (PDD) and with Lewy bodies (DLB) are clinically neuropathologically highly related α-synucleinopathies that collectively constitute the second leading cause of neurodegenerative dementias. Genetic neuropathological studies directly implicate α-synuclein (αS) abnormalities in PDD DLB pathogenesis. However, it is currently unknown how αS contribute to memory loss, particularly since forebrain neuronal loss less severe than Alzheimer's disease. Previously, we found...
ABSTRACT At cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction the glutamate transporter 1 (GLT‐1) in nucleus accumbens (NAc) has also been proposed as mechanism underlying addiction. However, impact GLT‐1 alterations NAc remain unclear. Here we show that 10 days withdraw after 5 treatment with cocaine or amphetamine decreases expression astrocytes, which results prolongation excitatory postsynaptic potential (EPSP)...
Rapid increases in the aging population present a critical challenge to global societies, with major concern being cognitive decline and brain aging. While neuroscientific research has traditionally focused on neurons, role of astrocytes is recent interest but remains underexplored. Astrocytes, homeostatic cells central nervous system, play essential roles synaptic regulation, neurotransmitter clearance, neuronal support, homeostasis. Recent studies indicate that undergo significant...
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of basal ganglia. Transcriptional perturbations synaptic genes neuroinflammation key processes that precede MSN dysfunction motor symptom onset. Understanding interplay between these crucial to develop effective therapeutic...
Abstract α-Synuclein is a major component of Lewy bodies (LB) and neurites (LN) appearing in the postmortem brain Parkinson's disease (PD) other α-synucleinopathies. While most studies α-synucleinopathies have focused on neuronal synaptic alterations as well dysfunctions astrocytic homeostatic roles, whether bidirectional astrocyte–neuronal communication affected these diseases remains unknown. We investigated astrocyte Ca 2+ excitability glutamatergic gliotransmission underlying signaling...
We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for treatment Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca(2+) channels, classically studied neurodegenerative diseases, Ser/Thr phosphatases, which have been marginally aimed, even despite key role in protein τ dephosphorylation. Twenty-five compounds were synthesized, mostly neuroprotective profile exceeded that offered by head...
Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, which astrocyte calcium signal plays a crucial role. Synaptically-evoked increases can be localized to independent subcellular domains or expand entire cell, i.e., surge. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because single contact ∼100,000 synapses, control intracellular propagation have relevant consequences on...
Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability from mice carrying ALS mutation SOD1(G93A) (mSOD1) also reported. Here we have investigated excitability, ion currents, and kinetics exocytotic fusion pore chromaffin cells postnatal day 90 to 130 mSOD1 mice, when motor deficits are already established. With respect wild-type (WT), had a decrease...
Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, which astrocyte calcium plays a crucial role. Synaptically evoked increases can be localized to independent subcellular domains or expand entire cell, i.e., surge. Because single may contact ~100,000 synapses, control of intracellular signal propagation have relevant consequences on function. Yet, properties governing spatial dynamics remains poorly defined. Imaging responses cortical...
As the peripheral sympathoadrenal axis is tightly controlled by cortex via hypothalamus and brain stem, central pathological features of Hunting's disease, (HD) that is, deposition mutated huntingtin synaptic dysfunctions, could also be expressed in adrenal chromaffin cells. To test this hypothesis we here present a thorough investigation on functional changes undergone cells (CCs) from 2-month (2 m) to 7-month (7 aged wild-type (WT) R6/1 mouse model Huntington's disease (HD), stimulated...
Amount evidence indicates that α7 nicotinic acetylcholine receptor (nAChRα7) activation reduces production of inflammatory mediators. This work aimed to verify the influence endogenous nAChRα7 on regulation full-blown muscular inflammation in mdx mouse with Duchenne dystrophy. We used mice 3 weeks-old at height myonecrosis, and C57 nAChRα7+/+ wild-type nAChRα7−/− knockout injury induced 60 µL 0.5% bupivacaine (bp) gastrocnemius muscle. Pharmacological treatment included selective agonist...
Upon repeated application of short ACh pulses to C57BL6J mouse chromaffin cells, the amperometrically monitored secretory responses promptly decayed a steady-state level around 25% initial response. A subsequent K+ pulse, however, overcame such decay. These data suggest that cells have ready release-vesicle pool is selectively recruited by physiological neurotransmitter ACh. The ACh-sensitive vesicle refilled and maintained rate Ca2+ delivery from mitochondria cytosol, through mitochondrial...
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an abnormal expansion of glutamine (Q) encoding CAG repeats in the ATAXIN1 (ATXN1) gene and characterized progressive cerebellar ataxia, dysarthria, eventual deterioration bulbar functions. SCA1 shows severe degeneration Purkinje cells (PCs) activation Bergmann glia (BG), astroglia closely associated with PCs. Combining electrophysiological recordings, calcium imaging techniques, chemogenetic approaches, we have...
Cultured bovine chromaffin cells have been used extensively as a neuroendocrine model to study regulated secretion. In order extend such experimental findings the physiological situation, it is necessary mayor cellular structures affecting secretion in cultured with their counterparts present adrenomedullary tissue. F-actin concentrates peripheral ring cells, witnessed by phalloidin-rodhamine labelling, while extends throughout cytosol native cells. This result also confirmed when studying...
The inhibition of nicotinic acetylcholine receptors (nAChRs) has been proposed as a potential strategy to develop new antidepressant drugs. This is based on the observation that antidepressants selectively block noradrenaline (NA) or serotonin (5-HT) reuptake also inhibit nAChRs. Dual blocking both NA and 5-HT were shorten delay in exerting their clinical effects; whether duloxetine, prototype dual antidepressants, blocks nAChRs unknown. Here we explored this question bovine chromaffin cells...
Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, which astrocyte calcium signal plays a crucial role. Synaptically-evoked increases can be localized to independent subcellular domains or expand entire cell, i.e., surge. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because single contact ∼100,000 synapses, control intracellular propagation have relevant consequences on...
Abstract Excitatory Amino Acid Transporters (EAATs), prominently expressed in astrocytes, are dynamic proteins crucial for synaptic function and plasticity, notably long-term depression (LTD). However, the precise adaptations glutamate uptake during LTD remain elusive. Within medial prefrontal cortex (mPFC), endocannabinoid (eCB) signaling assumes a central role ultimately affecting memory mood regulation. In CB1R activation increases intracellular Ca2+. We therefore hypothesize that...
Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, which astrocyte calcium plays a crucial role. Synaptically evoked increases can be localized to independent subcellular domains or expand entire cell, i.e., surge. Because single may contact ~100,000 synapses, control of intracellular signal propagation have relevant consequences on function. Yet, properties governing spatial dynamics remains poorly defined. Imaging responses cortical...