A5067561723- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Treatment of Major Depression
- Nuclear Receptors and Signaling
- Receptor Mechanisms and Signaling
- Schizophrenia research and treatment
- Anesthesia and Neurotoxicity Research
- Tryptophan and brain disorders
- Adipose Tissue and Metabolism
- Conducting polymers and applications
- Functional Brain Connectivity Studies
- Neuroscience and Neural Engineering
- Attention Deficit Hyperactivity Disorder
- Diet and metabolism studies
- Autism Spectrum Disorder Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Regulation of Appetite and Obesity
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
Institut d'Investigacions Biomèdiques de Barcelona
2016-2025
Consejo Superior de Investigaciones Científicas
2015-2025
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2016-2025
Centro de Investigación Biomédica en Red de Salud Mental
2016-2025
Instituto de Salud Carlos III
2014-2025
Research Network (United States)
2024
Biomedical Research Institute
2023
National University of Rosario
1998-2004
Abstract In Parkinson’s disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. humans, neuromelanin accumulates with age, the latter being main risk factor for PD. The contribution to PD pathogenesis remains unknown because, unlike common laboratory animals lack neuromelanin. Synthesis peripheral melanins mediated by tyrosinase, an enzyme also present at low levels in brain. Here we report that overexpression human...
Atypical antipsychotics increase dopamine (DA) release in the medial prefrontal cortex (mPFC), an effect possibly involved superior effects of atypical versus classical on cognitive/negative symptoms. We examined role 5-HT1A receptors mPFC modulation dopaminergic activity and mesocortical DA vivo. The highly selective agonist BAY x 3702 (BAY; 10-40 microg/kg, i.v.) increased firing rate burst neurons ventral tegmental area (VTA) VTA mPFC. both areas was potentiated by nomifensine...
Atypical antipsychotics show preferential 5-HT 2A versus dopamine (DA) D2 receptor affinity. At clinical doses, they fully occupy cortical 5-HT2 receptors, which suggests a strong relationship with their therapeutic action. Half of the pyramidal neurones in medial prefrontal cortex (mPFC) express receptors. Also, excited through receptors project to ventral tegmental area (VTA). We therefore hypothesized that can modulate DA transmission excitatory mPFC-VTA inputs. In this study we used...
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks Parkinson's disease (PD). Reduction levels is therefore a potential therapy for PD. However, because essential development function, elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration. Here,...
Summary Aims Glial cell‐derived neurotrophic factor (GDNF) is emerging as a potent with therapeutic potential against range of neurodegenerative conditions including Alzheimer's disease (AD). We assayed the effects GDNF treatment in AD experimental models through gene‐therapy procedures. Methods Recombinant lentiviral vectors were used to overexpress gene hippocampal astrocytes 3xTg‐AD mice vivo , and also MC65 human neuroblastoma that conditionally overexpresses 99‐residue carboxyl‐terminal...
The possible implication of transcription factor EB (TFEB) as a therapeutic target in Parkinson's disease has gained momentum since it was discovered that TFEB controls lysosomal biogenesis and autophagy its activation might counteract impairment protein aggregation. However, the majority putative direct targets described to date is linked range biological processes are not related lysosomal-autophagic system. Here, we assessed effect overexpressing with an adeno-associated viral vector...
Progressive neuronal death in monoaminergic nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks Parkinson's disease (PD). Given that may be an early mediator the pathological cascade ultimately leads to neurodegeneration, decreased synthesis will abate neurotoxicity if delivered key affected neurons.We used a non-viral gene therapy based on new indatraline-conjugated antisense oligonucleotide (IND-ASO) disrupt mRNA transcription selectively monoamine neurons...
Elevation of energy metabolism and disturbance astrocyte number/function in the ventral anterior cingulate cortex (vACC) contributes to pathophysiology major depressive disorder (MDD). Functional hyperactivity vACC may result from reduced astrocytic glutamate uptake increased neuronal excitation. Here we tested this hypothesis by knocking-down transporter GLAST/GLT-1 expression mouse infralimbic (IL, rodent equivalent vACC) or prelimbic (PrL) cortices using RNAi strategies. Unilateral siRNA...
Abstract Anxiety and depression affect 35–50% of patients with Parkinson’s disease (PD), often precede the onset motor symptoms, have a negative impact on their quality life. Dysfunction serotonergic (5-HT) system, which regulates mood emotional pathways, occurs during premotor phase PD contributes to variety non-motor symptoms. Furthermore, α-synuclein (α-Syn) aggregates were identified in raphe nuclei early stages disease. However, there are very few animal models PD-related...
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Abstract Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in origin mental disorders. Deficits GABAergic system prominently contribute to these alterations. Nav1.1 a voltage-gated Na+ channel critical for normal activity. Here, we studied role PFC its potential relationship with aetiology Dysfunction activity medial (mPFC) adolescent mice enhanced local excitation/inhibition ratio, resulting epileptic activity, cognitive deficits...
Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of 5-HT1A receptor (5-HT1AR). Given very low in-vitro affinity most APDs for 5-HT1ARs and large co-expression 5-HT2A receptors (5-HT2ARs) PFC, this might result from imbalance 5-HT1AR 5-HT2AR after blockade these APDs, which they show high affinity. Here we tested hypothesis examining dependence APD-induced DA medial PFC (mPFC) on...
The superior efficacy of atypical vs. classical antipsychotic drugs to treat negative symptoms and cognitive deficits in schizophrenia appears related their ability enhance mesocortical dopamine (DA) function. Given that noradrenergic (NE) transmission contributes cortical DA output, we assessed the NE-targeting modulate release medial prefrontal cortex (mPFC) nucleus accumbens (NAc), with aim selectively increasing DA. Extracellular was measured using brain microdialysis rat mPFC NAc after...
Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting serotonin transporter (SERT). As result, ~80% patients show recurrent or chronic depression, resulting in poor quality life increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used evoke antidepressant-like responses experimental animals. However, main limitation for medical use RNAi is extreme...