A5002352731- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neurotransmitter Receptor Influence on Behavior
- Nerve injury and regeneration
- Cholinesterase and Neurodegenerative Diseases
- Retinal Development and Disorders
- Neural dynamics and brain function
- Nuclear Receptors and Signaling
- Colorectal Cancer Treatments and Studies
- Quantum Dots Synthesis And Properties
- Protein Structure and Dynamics
- Infectious Encephalopathies and Encephalitis
- Biological Research and Disease Studies
- Optical Systems and Laser Technology
- Calpain Protease Function and Regulation
- Receptor Mechanisms and Signaling
- Cannabis and Cannabinoid Research
- Molecular Biology Techniques and Applications
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Cancer Treatment and Pharmacology
- Advanced optical system design
- Fuzzy Logic and Control Systems
- Memory and Neural Mechanisms
Lund University
2014-2024
Instituto Cajal
2024
Universidad de Alcalá
2024
Instituto Ramón y Cajal de Investigación Sanitaria
2024
Champalimaud Foundation
2024
Sorbonne Université
2008-2015
Institut du Fer à Moulin
2008-2015
Inserm
2008-2015
Université Paris-Sud
2009
Centre National de la Recherche Scientifique
2009
In the dopamine-depleted striatum, extracellular signal-regulated kinase (ERK) signaling is implicated in development of L-DOPA-induced dyskinesia. To gain insights on its role this disorder, we examined effects L-DOPA state phosphorylation ERK and downstream target proteins striatopallidal striatonigral medium spiny neurons (MSNs). For purpose, employed mice expressing enhanced green fluorescent protein (EGFP) under control promoters for dopamine D(2) receptor (Drd2-EGFP mice) or D(1)...
Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess movement in PD has been attributed to overactivity striatal projection neurons forming either the indirect (iSPNs) direct (dSPNs) pathway, respectively. Here, we investigated two pathways' contribution different features using SPN type-specific chemogenetic stimulation rodent models (PD mice) and...
Although L-3,4-dihydroxyphenylalanine (L-DOPA) remains the reference treatment of Parkinson's disease, its long-term beneficial effects are hindered by L-DOPA-induced dyskinesia (LID). In dopamine (DA)-denervated striatum, L-DOPA activates DA D₁ receptor(D₁R) signaling, including cAMP-dependent protein kinase A (PKA) and extracellular signal-regulated (ERK), two responses associated with LID. However, cause PKA ERK activation, their respective contribution to LID, relationship not known....
In animal models of Parkinson′s disease, striatal overactivation ERK1/2 via dopamine (DA) D1 receptors is the hallmark a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate pathways involved in receptor-dependent activation using acute slices from rodents unilateral 6-hydroxydopamine (6-OHDA) lesions. Application D1-like receptor agonist SKF38393 induced phosphorylation and downstream signaling DA-denervated but not intact striatum. This was mediated...
Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in hippocampus response administration D1-type receptor agonist, SKF 81297. 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings dentate gyrus revealed presence discharges peaking 30-45 min post-injection declining by 60 min. Seizures were prevented antagonist, SCH 23390, or cannabinoid CB1 CP 55,940. The effect was...
In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of l -DOPA-induced dyskinesia (LID). One major hypothesis that LID results from an aberrant transcriptional program in striatal neurons induced -DOPA and triggered activation ERK. To identify these genes, we performed transcriptome analyses striatum 6-hydroxydopamine-lesioned mice. A time course analysis (0–6 h after treatment with -DOPA) identified acute signature 709 among which genes involved...
Abstract The ability to form long‐term memories exists very early during ontogeny; however, the properties of memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine role extracellular signal‐regulated kinase (ERK), a member mitogen‐activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in consolidation reconsolidation an using conditioned taste aversion paradigm 3‐day‐old rat pups. We show that...
L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinsońs disease and the most common hyperkinetic disorder basal ganglia origin. Abnormal activity striatal D1 D2 spiny projection neurons (SPNs) critical for LID, yet link between SPN patterns specific dyskinetic movements remains unknown. To explore this, we developed novel method clustering based on high-resolution motion sensors video recordings. In mouse model this identified two main...
This procedure is meant to take place 3 weeks post lesion and viral injection.
L-DOPA drug treatment administered to mice for imaging and behavioral studies, see protocol- "Open-field experiments from Alcacer et al 2024" DOI: dx.doi.org/10.17504/protocols.io.6qpvr9e9bvmk/v1 is the protocol this used in.
Injection of 6-OHDA(6-Hydroxydopamine) or vehicle and virus injection protocol used in Alcacer et al.
Open field experimental set up and protocol for Alcacer et al 2024.
This protocol describes the tissue preparation and immunohistochemistry to verify extent of dopamine denervation from 6-OHDA injections check transfection efficiency GCamp6f-GFP vial construct that was injected into mouse brains.
Aims/Purpose: Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons, which occurs not only in the pars compacta sustantia nigra midbrain, but also retina, where amacrine cells (DAC) have been well characterized. Indeed, parkinsonian patients display visual impairments early stages disease, including motion perception deterioration. Retinal responsible are directional selective ganglion (DSGC) receive inhibitory synapses from starburst (SAC). Consequences DAC PD on...
To generate a mouse model of Parkinson's disease, unilateral injection 6-OHDA(6-hydroxydopamine) into the medial forebrain bundle (MFB) was performed. Three to four weeks later, drug-free cylinder test used assess extent lesion.