A5035769501- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Cholinesterase and Neurodegenerative Diseases
- Stress Responses and Cortisol
- Neurological disorders and treatments
- Laser Applications in Dentistry and Medicine
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- 3D Printing in Biomedical Research
- Anesthesia and Neurotoxicity Research
- Nerve injury and regeneration
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Inflammasome and immune disorders
- Biochemical effects in animals
- Adipose Tissue and Metabolism
- Olfactory and Sensory Function Studies
- Cancer-related gene regulation
- Parkinson's Disease Mechanisms and Treatments
Departament de Salut
2020-2025
Universitat de Barcelona
2019-2025
Biomedical Research Networking Center on Neurodegenerative Diseases
2019-2025
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2019-2025
Centro de Investigación Biomédica en Red
2024-2025
Instituto de Salud Carlos III
2024
Lund University
2020
It has been well documented that neurotrophins, including brain-derived neurotrophic factor (BDNF), are severely affected in Alzheimer9s disease (AD), but their administration faces a myriad of technical challenges. Here we took advantage the early astrogliosis observed an amyloid mouse model AD (5xFAD) and used it as internal sensor to administer BDNF conditionally locally. We first demonstrate relevance release from astrocytes by evaluating effects coculturing WT neurons BDNF-deficient...
The hippocampus is important for memory formation and severely affected in the brain with Alzheimer disease (AD). Our understanding of early pathogenic processes occurring hippocampi AD limited due to tissue unavailability. Here, we report a chemical approach rapidly generate free-floating hippocampal spheroids (HSs), from human induced pluripotent stem cells. When used model AD, both APP atypical PS1 variant HSs displayed increased Aβ42/Aβ40 peptide ratios decreased synaptic protein levels,...
Abstract Astrocytes have emerged as crucial regulators of neuronal network activity, synapse formation, and underlying behavioral cognitive processes. Despite some pathways been identified, the communication between astrocytes neurons remains to be completely elucidated. Unraveling this is design potential treatments for neurological disorders like temporal lobe epilepsy (TLE). The BDNF TrkB molecules very promising therapeutic targets. However, their modulation can accompanied by several...
N6-methyladenosine (m6A) regulates many aspects of RNA metabolism and is involved in learning memory processes. Yet, the impact a dysregulation post-transcriptional m6A editing on synaptic impairments neurodegenerative disorders remains unknown. Here we investigated methylation pattern hippocampus Huntington's disease (HD) mice potential role modification HD cognitive symptomatology. modifications were evaluated subjected to hippocampal training task through immunoprecipitation sequencing...
In the last two decades, microglia have emerged as key contributors to disease progression in many neurological disorders, not only by exerting their classical immunological functions but also extremely dynamic cells with ability modulate synaptic and neural activity. This behavior, together heterogeneous roles response diverse perturbations brain parenchyma has raised idea that activation is more than anticipated understanding molecular mechanisms underlying microglial states essential...
Chronic stress is an important risk factor for the development of major depressive disorder (MDD). Recent studies have shown microbiome dysbiosis as one pathogenic mechanisms associated with MDD. Thus, it to find novel non-pharmacological therapeutic strategies that can modulate gut microbiota and brain activity. One such strategy photobiomodulation (PBM), which involves non-invasive use light.
RTP801/REDD1 is a stress-regulated protein whose upregulation necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson's Huntington's disease models ameliorates the pathological phenotypes. In context of Alzheimer's (AD), coding gene for RTP801, DDIT4, responsive Aβ modulates its cytotoxicity vitro. Also, RTP801 mRNA levels are increased AD patients' lymphocytes. However, involvement pathophysiology has not been yet tested. Here, we demonstrate that postmortem...
Chronic stress is a core risk factor for developing myriad of neurological disorders, including major depression. The chronicity such can lead to adaptive responses or, on the contrary, psychological maladaptation. hippocampus one most affected brain regions displaying functional changes in chronic stress. Egr1, transcription involved synaptic plasticity, key molecule regulating hippocampal function, but its role stress-induced sequels has been poorly addressed. Emotional and cognitive...
Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30% of affected individuals frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as potential safe therapeutic option alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects not yet fully...
Major depressive disorder (MDD) is a common with variety of symptoms including mood alterations, anhedonia, sleep and appetite disorders, cognitive disturbances. Stressful life events are among the strongest risk factors for developing MDD. At cellular level, chronic stress results in modification dendritic spine morphology density. Here, we study role Pyk2 development depressive-like induced by model unpredictable mild (CUMS). non-receptor calcium-dependent protein-tyrosine kinase highly...
The characterization of highly conserved but poorly understood genes often reveals unexpected biological roles, advancing our understanding disease mechanisms. One such gene is Mammalian TatD DNase domain containing 1 ( Tatdn1 ), the mammalian homolog bacterial Twin‐arginine translocation D (TatD), a protein proposed to have roles either in DNA degradation or quality control unicellular organisms. Despite its association with different pathologies, including several cancer types and...
Motor skills learning is classically associated with brain regions including cerebral and cerebellar cortices basal ganglia nuclei. Less known about the role of hippocampus in acquisition storage motor skills. Here, we show that mice receiving a long-term training accelerating rotarod display marked hippocampal transcriptional changes reduced pyramidal neurons activity CA1 region when compared naive mice. Then, use which neural ensembles are permanently labeled an <i>Egr1</i>...
Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related stress, Huntington's disease, Alzheimer's disease. All these disorders are accompanied by different types of impairments sociability, which recently linked improper mitochondrial function. We hypothesize that Pyk2, regulates mitochondria, could associated with the regulation dynamics social skills. In present manuscript, we report a reduction levels mouse pyramidal neurons hippocampus...
ABSTRACT The alterations in the basal ganglia circuitry associated with motor symptoms Huntington’s Disease (HD) have been extensively investigated. Yet, specific contribution of direct and indirect striatal output pathways from dorsolateral (DLS) dorsomedial striatum (DMS) to dysfunction is still not fully understood. Here, using symptomatic R6/1 male mouse model HD, strong functional connectivity between DMS DLS regions rest brain were observed by fMRI, particularly pronounced DLS. Then,...
Glycogen synthase kinase 3β (GSK3β) is a core protein, with relevant role in many neurodegenerative disorders including Alzheimer’s disease. The enzyme has been largely studied as potential therapeutic target for several neurological diseases. Unfortunately, preclinical and clinical studies GSK3β inhibitors have failed due to reasons such excessive toxicity or lack of effects human subjects. We previously reported that meridianins are potent without altering neuronal viability. In the...
Summary Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs mouse a controlled spatio-temporal manner two different scenarios: development, and adult stages context of neurodegeneration. Embryonic induction perturbed cell identity both progenitors neurons, transient low-level expression is tolerated by these cells during development. Under conditions, led to expanded neurogenesis,...
The alterations in the basal ganglia circuitry are core pathological hallmark Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences striatum is able reverse symptoms HD mice. However, specific contribution direct indirect striatal output pathways from dorsolateral (DLS) dorsomedial (DMS) phenotype still not clear. Here, we aim uncover contributions these subcircuits control wild type (WT) mice...
The role of the WDFY1 protein has been studied as a TLR3/4 scaffold/recruiting in immune system and different oncogenic conditions, however, its function brain remains poorly understood. We have found that mice devoid Helios (He-/- mice), transcription factor specifically expressed during development cells central nervous system, there is permanent sustained increase Wdfy1 gene expression striatum hippocampus. Interestingly, we observed levels were also increased hippocampus dorsolateral...
Abstract Background Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum major hallmark disease. Approximately 30% those inputs come from thalamic nuclei. Foxp2 transcription factor involved in cell differentiation and reported low patients with HD. However, role thalamus HD remains unexplored. Methods We used two different mouse models HD, R6/1 HdhQ111 mice, to demonstrate consistent reduction context vivo...
RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's (HD). RTP801 downregulation ameliorates behavioral abnormalities mouse models of these disorders. In HD, mediates mutant huntingtin (mhtt) toxicity vitro its human iPSCs, postmortem putamen samples, striatal synaptosomes from the disease. Here, we investigated role hippocampal pathophysiology HD. We found that hippocampus HD patients...
Schizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 IKZF2, classic immune-related transcription factors (TFs), were both downregulated patients peripheral blood mononuclear cells (PBMCs) but not their brain. generated new mutant mouse model with reduction Ikzf1 Ikzf2 to study impact those changes. Such mice developed deficits three dimensions (positive-negative-cognitive)...