Biology subjects

Ribera, A.

Publications and source records attributed to Ribera, A..

4 recordsLinked to original sources

bioRxiv2026

Reinforced Hippocampus-Accumbens pathway marks a shift towards cognitive decline in aging

Aging triggers early functional alterations in brain circuits that precede cognitive impairment, yet the underlying mechanisms remain unclear. Spatial navigation and memory, among the earliest affected, depend on hippocampus and downstream targets such as the nucleus accumbens (NAc), which integrates spatial and motivational information to guide goal-directed behaviors. Here we identify age-related, sex-dependent changes of the dorsal hippocampus-NAc (dHPC[->]NAc) pathway. Combining optogenetics with electrophysiology, chemogenetics, and behavioral analyses in mice, we show that aging shifts excitation-inhibition balance in dorsal CA1 toward pyramidal neuron hyperexcitability, strengthening hippocampal outputs. This selectively enhances synaptic drive onto D1 receptor-expressing medium spiny neurons and involves a previously unrecognized long-range parvalbumin-expressing glutamatergic projection. Reducing dHPC[->]NAc excitability improves memory in aged mice. In humans, fMRI reveals heightened posterior hippocampal activity and stronger pHPC-NAc coupling during navigation. Together, we uncover a targetable pathway acting in an intervention-sensitive window of aging to correct negative cognitive trajectories.

neuroscience↗

bioRxiv2025

Bdnf-Ntrk2 Signaling Promotes but is not Essential for Spinal Cord Myelination in Larval Zebrafish

Myelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.

developmental biology↗

bioRxiv2022

Age-dependent NMDA receptor function is regulated by the Amyloid Precursor Protein

N-methyl-D-aspartate receptors (NMDARs) are critical for the maturation and plasticity of glutamatergic synapses. In the hippocampus, NMDARs mainly contain GluN2A and/or GluN2B regulatory subunits. The amyloid precursor protein (APP) has emerged as a putative regulator of NMDARs, but the impact of this interaction to their function is largely unknown. By combining patch-clamp electrophysiology and molecular approaches, we unravel a dual mechanism by which APP controls GluN2B-NMDARs, depending on the life stage. We show that APP is highly abundant specifically at the postnatal postsynapse. It interacts with GluN2B-NMDARs, controlling its synaptic content and mediated currents, both in infant mice and primary neuronal cultures. Upon aging, the APP amyloidogenic derived C-terminal fragments, rather than APP full length, contribute to aberrant GluN2B-NMDAR currents. Accordingly, we found that the APP processing is increased upon aging, both in mice and human brain, and interfering with this mechanism normalized the aberrant currents. While the first mechanism might be essential for synaptic maturation during development, the latter could contribute to age-related synaptic impairments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/500736v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1c4d540org.highwire.dtl.DTLVardef@18c7b67org.highwire.dtl.DTLVardef@1f9e482org.highwire.dtl.DTLVardef@109274f_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefRajao-Saraiva et al. identified the APP full-length protein as a regulator of glutamatergic transmission in immature synapses, by controlling GluN2B synaptic content and mediated currents during postnatal development. Upon aging, the APP amyloidogenic derived C-terminal fragments, rather than APP full length, contribute to aberrant GluN2B-NMDAR currents. Our work highlights the importance of keeping APP processing under tight control, to ensure the normal functioning of glutamatergic synapses, being particularly relevant to understand age-related synaptic impairments and AD.

neuroscience↗

bioRxiv2018

Non-intravenous, carbapenem-sparing antibiotics for the treatment of bacteremia due to ESBL or AMP-C β-lactamase: A propensity score study

IntroductionCarbapenems are considered the treatment of choice for extended-spectrum {beta}-lactamase (ESBL) or Amp-C {beta}-lactamase-producing Enterobacteriaceae bacteremia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited.\n\nObjectiveTo compare the 30 day-mortality and clinical failures associated with the use of carbapenems vs an alternative non-intravenous antibiotic for the definitive treatment of ESBL/Amp-C positive Enterobacteriaceae bacteremia.\n\nMethodsThis is a 12-year retrospective study (2004 - 2015) including all patients with bacteremia due to ESBL/Amp-C-producing Enterobacteriaceae. Given the lack of randomization of the initial therapies, a propensity score for receiving carbapenems was calculated.\n\nResultsThere were 1115 patients with a first episode of bacteremia due to E. coli or K. pneumoniae, of which 123 were ESBL/Amp C-positive (11%). There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (cotrimoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared to the carbapenem group, patients treated with the alternative regimen had a shorter hospital stay (median [IQR]: 7 days [5-10] vs 12 days [9-18], p<0,001). The use of an alternative non-IV treatment did not increase mortality (OR 27; 95% CI 0.05-1.61; p=.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95; 95% CI (0.9426.01, p=.059).\n\nConclusionAlternative non-IV carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/Amp-C-positive Enterobacteriaceae bloodstream infections, allowing a reduction in carbapenem use. The use of cotrimoxazole in this setting has shown favourable results.\n\nSome of the data contained in this article were presented at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and at the 28th International Congress of Chemotherapy Meeting (ICC), San Diego, USA, 2015.

pathology↗