Biology subjects

Oz, O.

Publications and source records attributed to Oz, O..

3 recordsLinked to original sources

bioRxiv2026

Internet-delivered cognitive behavioral therapy is associated with distinct blood small RNA profiles in panic disorder

Panic disorder associates with altered fear circuitry, autonomic dysregulation and stress-related immune perturbations, yet its molecular and treatment-response signatures remain poorly defined. Internet-delivered cognitive behavioral therapy (iCBT) is an effective first-line treatment with unexplained outcome variations across individuals. Here, we report altered profiles of small non-coding RNAs in peripheral blood mononuclear cells from panic disorder patients before and after iCBT, compared with longitudinally sampled healthy controls. Thirteen top-ranking microRNAs discriminated patients from controls and separated pre- and post-treatment states, both of which differed from controls. Correspondingly, baseline hsa-miR-125b-5p levels were significantly associated with post-iCBT symptom improvement. Transfer RNA-derived fragments (tRFs) showed even greater discriminatory power, with nuclear-Val-3'-tRF family members exhibiting a pronounced post-treatment shift. Pathway analyses of panic disorder-associated and CBT-responsive small RNA targets converged on immune-related pathways, supporting a role in inflammatory mechanisms and highlighting blood small non-coding RNAs as promising biomarkers of panic disorder and its therapeutic response.

molecular biology↗

bioRxiv2021

Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons

The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.

neuroscience↗

bioRxiv2021

Adiponectin Preserves Metabolic Fitness During Aging

Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet (HFD). In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.

cell biology↗