Biology subjects

Paz, V.

Publications and source records attributed to Paz, V..

4 recordsLinked to original sources

bioRxiv2025

A molecular convergence in the triad of Parkinson's disease, depressive disorder and gut health is revealed by the inflammation-miRNA axis

BackgroundParkinsons disease (PD) is a multisystem disorder frequently comorbid with non-motor symptoms like depressive disorder (DD) and gastrointestinal (GI) dysfunction. Chronic neuroinflammation and disruption of the gut-brain axis are implicated as shared pathological drivers, but the precise molecular mechanisms connecting these conditions remain elusive. We hypothesized that a common microRNA (miRNA)-mediated inflammatory profile underlies this clinical triad, representing a point of pathological convergence. MethodsWe analyzed the expression of a panel of inflammatory bowel disease (IBD)-associated miRNAs, key inflammatory markers, and glial response in postmortem brain tissue (dorsolateral prefrontal cortex and caudate nucleus) from patients with PD, DD, and matched healthy controls. To investigate causality and gut-brain axis involvement, two mouse models were used: (i) PD-associated -synucleinopathy was induced in dorsal raphe serotonin (5-HT) neurons; and (ii) DD-like based on corticosterone (CORT)-induced stress. Mice were assessed for depressive-like behaviors and GI dysmotility, and their brain (medial prefrontal cortex and caudate-putamen) and ileum tissues were analyzed for the same molecular markers. ResultsWe identified a conserved miRNA pattern in the brains of both PD and DD patients, characterized by the significant downregulation of miR-199a-5p and miR-219a-5p and the upregulation of miR-200a-3p. This dysregulation was strongly associated with a pro-inflammatory state, as evidenced by increased expression of TNF, IFN-{gamma}, and NF{kappa}B1, as well as changes in the glial response. Mice with -synucleinopathy in the 5-HT system exhibited a depression-like phenotype and reduced intestinal motility, accompanied by increased Iba1 and GFAP signal. Comparable effects were observed in mice subjected to CORT-induced stress. Notably, the same pattern of miRNAs and inflammatory cytokines observed in the human brain was replicated in the brain and ileum of DD-PD-like mice, providing direct evidence of a parallel pathological process spanning the gut-brain axis. ConclusionThis study identifies a specific miRNA-inflammatory axis as a common molecular mechanism connecting the pathophysiology of PD, DD, and gut dysfunction. This pattern represents a critical point of convergence that drives a shared, bidirectional inflammatory cascade along the gut-brain axis. Targeting this miRNA triad could provide a new therapeutic approach for addressing the motor, psychiatric, and GI symptoms of these interconnected disorders simultaneously.

neuroscience↗

bioRxiv2025

Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype

Anxiety and depression are common in Parkinsons disease (PD), affecting quality of life. Aggregates of -synuclein (-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human -Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with -Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.

neuroscience↗

bioRxiv2019

Neural signals relating future cooperation from prisoner’s dilemma feedback are outcome-contingent

Electing whether to cooperate with someone else is well typified in the iterated prisoners dilemma (iPD) game, although the neural processes that unfold after its distinct outcomes have been only partly described. Recent theoretical models emphasize the ubiquity of intuitive cooperation, raising questions on the neural timelines involved. We studied the outcome stage of an iPD with electroencephalography (EEG) methods. Results showed that neural signals that are modulated by the iPD outcomes can also be indicative of future choice, in an outcome-dependent manner: (i) after zero-gain suckers payoffs (unreciprocated cooperation), a participants decision thereafter may be indicated by changes to the feedback-related negativity (FRN); (ii) after one-sided non-cooperation (participant gain), by the P3; (iii) after mutual cooperation, by late frontal delta-band modulations. Critically, faster choices to reciprocate cooperation were predicted, on a single-trial basis, by P3 and frontal delta modulations at the immediately preceding trial. Delta band signaling is considered in relation to homeostatic regulation processing in the literature. The findings relate feedback to decisional processes in the iPD, providing a first neural account of the brief timelines implied in heuristic modes of cooperation.

neuroscience↗

bioRxiv2019

Oropouche virus cases identified in Ecuador using an optimised rRT-PCR informed by metagenomic sequencing

Oropouche virus (OROV) is responsible for outbreaks of Oropouche fever in parts of South America. We recently identified and isolated OROV from a febrile Ecuadorian patient, however, a previously published rRT-PCR assay did not detect OROV in the patient sample. A primer mismatch to the Ecuadorian OROV lineage was identified from metagenomic sequencing data. We report the optimisation of an rRT-PCR assay for the Ecuadorian OROV lineage, which subsequently identified a further five cases in a cohort of 196 febrile patients. We isolated OROV via cell culture and developed an algorithmically-designed primer set for whole-genome amplification of the virus. Metagenomic sequencing of the patient samples provided OROV genome coverage ranging from 68 - 99%. The additional cases formed a single phylogenetic cluster together with the initial case. OROV should be considered as a differential diagnosis for Ecuadorian patients with febrile illness to avoid mis-diagnosis with other circulating pathogens.

genomics↗