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Perez, R. A.

Publications and source records attributed to Perez, R. A..

3 recordsLinked to original sources

Gelsolin protects mitochondria and regulates inflammation during Legionella pneumophila infection

Legionella pneumophila (L. pneumophila) is the causative agent of Legionnaires' disease, a severe bacterial pneumonia. Difficulty in diagnosing Legionnaires' disease leads to an underreporting of cases and delayed treatment. Rapid-acting, broad-spectrum therapies are needed to treat pathology while avoiding antibiotic resistance. We showed that gelsolin knockout (gsn-/-) mice succumb more quickly to severe L. pneumophila infection despite no difference in bacterial loads in the lung compared to wild type mice. There is an increase in CXCL1/KC production from macrophages from gsn-/- mice, which is accompanied by increased neutrophils and apoptosis in their lungs. Neutrophils lacking gelsolin produce fewer neutrophil extracellular traps, and their mitochondrial capacity is diminished in response to L. pneumophila. Gelsolin is required for maintaining mitochondrial network morphology and respiration in L. pneumophila infected macrophages. When given recombinant gelsolin protein, gsn-/- mice survive significantly longer during severe L. pneumophila infection, with reduced lung pathology, and the inflammatory signature of their macrophages was reduced in vitro. Together, gelsolin protects mice during severe L. pneumophila infection, dampens inflammation, promotes mitochondrial health, and maintains neutrophil function.

immunology↗

Macroscale dynamics of EEG microstates determine the periodic and aperiodic features of the neural power spectrum

The global signal characteristics of scalp-recorded electroencephalography (EEG) are composed of periodic oscillatory rhythms and aperiodic broadband fluctuations that together constitute the neural power spectrum. Spectral decomposition of these features has long served as the primary window into the macroscale characteristics of human brain activity. However, prevailing interpretations of spectral features lack a unifying mechanistic framework and often conflate activity resulting from distinct neural sources. Here, we propose that the primary periodic rhythms and majority share of broadband spectral power within the brains dominant frequencies originate from the brain network architecture responsible for generating EEG microstates. These microstates consist of a small repertoire of quasi-stable topographic voltage configurations that each reflect the momentary functional state of the cortex, and it is their dynamics that generate periodic and aperiodic spectral features. To computationally test this generating mechanism, we isolated and removed the spatial projections of microstates from high-density EEG using orthogonal subspace projection applied to both the surface scalp recordings and their modeled cortical generators. Spectral parameterization of the residual power spectral density revealed that removing seven distinct microstates strongly attenuated alpha and theta rhythms and features of the aperiodic 1/f background. Selectively removing specific topographic configurations also demonstrated that each microstate possesses independent oscillatory generators and unique 1/f aperiodic structures. Together, our findings suggest that dominant periodic and aperiodic spectral features are more accurately understood as the frequency-domain expressions of the distributed brain networks generating EEG microstates.

neuroscience↗

Modulation of microRNA-502-3p significantly influences synaptic activity, dendritic spine density and mitochondrial morphology in the mice brain

Synapse dysfunction is the root cause of Alzheimers disease (AD). Uninterrupted and regulated synapse action is crucial to maintain healthy brain function. Our previous study discovered microRNA-502-3p (miR-502-3p), a synapse-specific miRNA, highly expressed at the AD synapses. Further, in vitro studies unveiled the biological relevance of miR-502-3p in modulating GABA receptor function, synaptic activity and mitochondrial morphology. Current study focuses to investigate the role of miR-502-3p in vivo using stereotaxic injection of miR-502-3p overexpression (OE) and suppression (sponge) lentivirus (LV) into the hippocampus of C57BL/6 wild-type (WT) mice. MiR-502-3p OE and sponge LV were characterized by transducing HT22 cells followed by QRT-PCR and miRNAScope analysis of miR-502-3p. MiR-502-3p OE LV showed a very high-fold upregulation and sponge LV showed significant reduction in miR-502-3p levels. MiR-502-3p OE and sponge LV were injected into three months old WT mice brain hippocampus. Overexpression and suppression effects of miR-502-3p were studied on synaptic proteins, synapse number, mitochondrial morphology and dendritic spine density at eight-weeks post-injection. Mice injected with miR-502-3p OE LV showed reduced levels of synaptic proteins, diminished synapse formation, defective mitochondrial morphology and reduced dendritic spine density relative to control LV treated mice. While mice treated with sponge LV showed elevated levels of synaptic proteins, augmented synapses, improved mitochondrial morphology and elongated dendrites and spine density. Our in vivo study unveiled translational abilities of miR-502-3p to restore synapse dysfunction in AD and other neurological disorders.

neuroscience↗