Amorim, D. R. | Search bioRxiv

bioRxiv2025

Upregulation of voltage-gated potassium channels in peripheral blood mononuclear cells: a new approach to multiple sclerosis treatment

Multiple sclerosis (MS) involves immune dysregulation and abnormal ion channel function. This study investigated the expression and function of voltage-gated potassium (Kv) channel isoforms (Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3, Kv7.2) in peripheral blood mononuclear cells (PBMCs) and lymphocytes from MS patients (remittent-recurrent) compared to controls. We found an upregulation of in six out of seven Kv isoforms in PBMCs from MS patients, with sex-specific differences observed (female showing a more pronounced upregulation of specific isoforms). Electrophysiological analysis of CD3+ T lymphocytes showed no significant differences, while CD19+ B lymphocytes displayed a notable decrease in outward current density. These findings suggest potential variations in Kv channel function across immune cell types and highlight the need for further exploration of their roles in MS pathogenesis, particularly within B lymphocytes and considering sex-based considerations.

molecular biology↗

bioRxiv2024

Multisensory gamma stimulation enhances adult neurogenesis and improves cognitive function in a mouse model of Down syndrome

Down syndrome (DS) has been linked with deficits in hippocampal dependent cognitive tasks and adult neurogenesis, yet treatment options are still very limited. We and others previously showed that a non-invasive multisensory gamma stimulation using light and sound at 40 Hz ameliorated Alzheimers disease pathology and symptoms in mouse models. In this study, we tested the effects of 40 Hz multisensory stimulation in the Ts65Dn mice, a mouse model of DS. For three weeks, mice were exposed daily to one hour of stimulation or one hour of ambient light and sound. Mice receiving the stimulation showed improved object recognition and spatial working memory. Using single nuclei RNA-seq and experimental validations in mouse hippocampal samples, we identified underlying expression changes in gene regulatory networks and demonstrated increased adult neurogenesis and reorganization of synapses as potential mechanisms for these improved cognitive phenotypes. Together, our data reveal a novel effect of multisensory gamma stimulation on adult neurogenesis and beneficial effects of 40 Hz treatment on cognitive function in DS model mice. Significance StatementWe present strong evidence, using a well-characterized mouse model, that the cognitive and neurogenesis deficits in Down syndrome can be improved through non-invasive multi-sensory gamma stimulation. Employing a systems biology approach, we provide extensive hippocampal single-cell resolution gene expression signatures and changes in gene regulatory networks in response to sensory gamma stimulation.

neuroscience↗