Biology subjects

Barrio-Alonso, E.

Publications and source records attributed to Barrio-Alonso, E..

3 recordsLinked to original sources

bioRxiv2025

Astrocytic RNA degradation suppresses calcium signaling to support synapse function and restrain anxiety

How astrocytes achieve their diverse roles in the brain at the molecular level is poorly understood. In this study, we leverage mouse models, electrophysiology, calcium imaging, behavioral assays, and bioinformatic approaches to demonstrate that astrocyte activity and astrocyte-mediated mouse behavior depends on the highly conserved and selective RNA turnover pathway-nonsense-mediated RNA decay (NMD). Conditional deletion of the core NMD gene, Upf2, in mature astrocytes leads to enhanced basal Ca2+ signaling coupled with synapse dysfunction and elevated anxiety. Restoring basal Ca2+ signaling in NMD-deficient astrocytes rescued synaptic transmission and minimized anxiety-associated behavior. Molecular bioinformatic analysis identified specific NMD target transcripts in astrocytes as candidates influencing calcium signaling pathways and neuro-glia interactions that support brain function. Our study is the first to demonstrate specific roles for NMD in astrocytes.

neuroscience↗

bioRxiv2021

Astrocytes derived from ASD patients alter behavior and destabilize neuronal activity through aberrant Ca2+ signaling

The cellular mechanisms of Autism Spectrum Disorder (ASD) are poorly understood. Cumulative evidence suggests that abnormal synapse function underlies many features of this disease. Astrocytes play in several key neuronal processes, including the formation of synapses and the modulation of synaptic plasticity. Astrocyte abnormalities have also been identified in the postmortem brain tissue of ASD patients. However, it remains unclear whether astrocyte pathology plays a mechanistic role in ASD, as opposed to a compensatory response. To address this, we strategically combined stem cell culturing with transplantation techniques to determine disease specific properties inherent to patient derived astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. These in vivo phenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neurons in vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+ fluctuations in chimeric brains. Genetic modulation of evoked Ca2+ responses in ASD astrocytes modulates behavior and neuronal activity deficits. Thus, we determine that ASD patient astrocytes are sufficient to induce repetitive behavior as well as cognitive deficit, suggesting a previously unrecognized primary role for astrocytes in ASD.

neuroscience↗

bioRxiv2018

Checkpoint signaling abrogation after cell cycle reentry reveals that differentiated neurons are mitotic cells

Mitotic activity associated to neuron cell-death instead of cell-division is reported in neurodegenerative diseases. However, why mitotic activity can take place in supposedly postmitotic neurons and how it is associated to cell-death remains largely unexplained. To address these questions, we have studied the response of primary neurons to oncogenic deregulation using a fusion protein based on truncated Cyclin E and Cdk2. Oncogenic Cyclin E/Cdk2 elicits mitotic checkpoint signaling, resulting in cell-cycle arrest and cell-death. However, as in mitotic cells, checkpoint suppression enables oncogenic cell-cycle progression and neuronal division. Further, neurons actively adapt to the cell-cycle by losing and reforming the axon initial segment, which integrates synaptic inputs to sustain action potentials. We conclude that neurons are mitotic cells in a reversible quiescent-like state, which is falsely portrayed as irreversible by mitotic checkpoints. In extension, neuronal death in lieu of cell-division reflects oncosuppressive checkpoint signaling.

neuroscience↗