Biology subjects

Counts, S. E.

Publications and source records attributed to Counts, S. E..

5 recordsLinked to original sources

bioRxiv2026

Aberrant neuronal cell cycle re-entry induces late-onset Alzheimer's disease relevant neuropathological and gene expression changes

Aberrant neuronal cell cycle re-entry (NCCR) is an alternative pathogenic mechanism in Alzheimer disease (AD) that has gained substantial support in the literature. The pathogenic role of ectopic NCCR is supported by our past work demonstrating that SV40T-mediated NCCR in adult mice can induce numerous pathologies associated with AD. Since NCCR is chronically induced for an extended period in the mouse model which gives rise to numerous pathologies including neuroinflammation, many of these neuropathological changes could simultaneously participate in driving disease progression. We hypothesized that the NCCR is a primary pathogenic driver and that halting this disease process at a later age could be sufficient for preventing the progression of AD-related pathologies. Here we show that modulation of NCCR at a later age prevents the progression of AD pathologies, including Abeta; and tau pathologies. Furthermore, functional genomics analysis demonstrates the late-onset AD (LOAD)-relevance of NCCR. Our findings suggest that our NCCR mouse model could help identify novel therapeutic targets that could aid in preventing AD progression.

neuroscience↗

bioRxiv2026

MicroRNA-181 influences Alzheimer's risk by regulating neprilysin and microtubule-associated tau pathways, offering a novel target

Alzheimers disease (AD) is characterized by amyloid-{beta} (A{beta}) peptide plaques and neurofibrillary tangles from hyperphosphorylated tau, though factors linking amyloid and tau pathology remain unclear. We investigated whether microRNA-181d-5p (miR-181d) associates with AD-related brain changes and regulates neprilysin and tau. Modeling miR-181d across individuals with no cognitive impairment, mild cognitive impairment, and AD revealed region- and sex-specific associations. Higher miR-181d levels associated with greater AD probability in the temporal lobe and cerebellum, and lower probability in the posterior cingulate cortex of males; miR-181c attenuated these probabilities. SNPs near MIR181 associated with altered entorhinal cortical thickness. In cellular models, miR-181 reduced neprilysin 3'-UTR activity, mRNA, protein, and enzymatic activity, while increasing tau mRNA and protein. Neprilysin diminution impairs A{beta} clearance and elevates tau, contributing to AD. RNA sequencing identified miR-181d-responsive neurodegenerative pathways. These findings identify miR-181 as a regulator of AD-relevant amyloid and tau pathways, providing novel targets. TeaserMiRNA-181 is a key regulator of Alzheimers risk through its effects on neprilysin and tau proteins, a novel potential target.

neuroscience↗

bioRxiv2025

Burnout in nurses and biomarkers of stress, inflammation and neuroplasticity.

Burnout is an occupational challenge to the health, performance, and retention of healthcare personnel. The objective of this cross-sectional study was to further our understanding of the association between burnout, work, coping, and cognitive impairment as it relates to neuroendocrine, inflammatory, and neuroplastic disease mechanisms. One hundred hospital- based registered nurses responded to a validated survey addressing employment and work characteristics, coping, and cognitive impairment, and a one-item, burnout scale. In addition, they all provided blood samples. Nineteen percent of the nurses reported symptoms of evolving burnout and an additional 12% reported established burnout. Severity of burnout was inversely associated with self-rated energy (p<.001), ability to concentrate (p<.001), and positively associated with stressed at work (p<.001), but not with workplace cognitive impairment. The anti-inflammatory and pro-energetic biomarker interleukin-10 was elevated in respondents in the combined two highest burnout categories (mean 2.81, S.E.M. 0.26 pg/mL) vs. a median of 2.09 pg/mL in the no-burnout category (p<.02). When biomarkers in blood were regressed on severity of burnout, concentration of the anabolic hormone dehydroepiandrosterone-sulfate (standardized beta -.73, p=.007) and the neuronal strain biomarker neurofilament light chain (-.79, p=.01) inversely predicted burnout. In contrast, the ability to cope with a tough situation at work was positively associated with burnout (.75, p=.02). The study not only confirms the association between burnout and self-reported individual and work-related adverse outcomes but, importantly, burnout-relevant neuroendocrine, inflammatory, and neuronal biomarkers. Nurses suffering from burnout might exhibit dysfunctional coping resulting in decreased recognition of low energy, which accelerates the burnout process. It is proposed that assessment of biological disease mechanisms should play a larger role in both scholarly and clinical burnout work.

neuroscience↗

bioRxiv2024

Human microRNA-153-3p targets specific neuronal genes and is associated with the risk of Alzheimer's disease.

Alzheimers disease (AD) is a progressive degenerative disease characterized by a significant loss of neurons and synapses in cognitive brain regions and is the leading cause of dementia worldwide. AD pathology comprises extracellular amyloid plaques and intracellular neurofibrillary tangles. However, the triggers of this pathology are still poorly understood. Repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF), a transcription repressor of neuronal genes, is dysregulated during AD pathogenesis. How REST is dysregulated is still poorly understood, especially at the post-transcriptional level. MicroRNAs (miRNAs), a group of short non-coding RNAs, typically regulate protein expression by interacting with target mRNA transcript 3-untranslated region (UTR) and play essential roles in AD pathogenesis. Herein, we demonstrate that miR-153-3p reduces REST 3-UTR activities, mRNA, and protein levels in human cell lines, along with downregulating amyloid-{beta} precursor protein (APP) and -synuclein (SNCA). We determine by mutational analyses that miR-153-3p interacts with specific targets via the seed sequence present within the respective mRNA 3UTR. We show that miR-153-3p treatment alters the expression of these specific proteins in human neuronally differentiated cell lines and human induced pluripotent stem cells and that miR-153-3p is itself dysregulated in AD. We further find that single nucleotide polymorphisms (SNPs) within 5kb of the MIR153-1 and MIR153-2 genes are associated with AD-related endophenotypes. Elevation of miR-153-3p is associated with a reduced probability of AD, while elevated REST may associate with a greater probability of AD. Our work suggests that a supplement of miR-153-3p would reduce levels of toxic protein aggregates by reduced expression of APP, SNCA and REST expression, all pointing towards a therapeutic and biomarker potential of miR-153-3p in AD and related dementias.

neuroscience↗

bioRxiv2022

Novel inductively-coupled ear-bars (ICEs) for fMRI signal enhancement in rat entorhinal cortex

Entorhinal cortex (EC) is a potential target of deep brain stimulation in Alzheimers disease (AD) and fMRI can enable whole-brain dynamic mapping noninvasively. However, it remains challenging to study EC-based fMRI connectivity in rodents due to image signal loss and the lower sensitivity of the surface coil ring or array coil for deep brain areas. To reduce the magnetic susceptibility artifacts driven signal loss issue, we introduced baby cream into the middle ear. To improve detection sensitivity, we implemented novel inductively-coupled ear-bars (ICEs) in the 7 T Bruker scanner, which resulted in an approximately 2-fold signal-to-noise ratio (SNR) increase in EC over the conventional surface array. The ICE can be conveniently utilized as an add-on device, with no modulation to the scanner interface. To demonstrate the applicability of ICEs for both task and resting-state (rs) fMRI, whole-brain echo-planar imaging (EPI) was performed in anesthetized rats modeling AD mixed dementia. Seed-based rs-fMRI connectivity maps emanating from the left entorhinal cortex demonstrated its connectivity to the hippocampus, piriform cortex, septal nuclei, and prefrontal cortex. Hence, this work demonstrates an optimized procedure for ICE by acquiring large scale networks emanating from a seed region that was not easily accessible by conventional MRI detectors, enabling better observation of EC-based brain fMRI connectivity studies with a higher signal-to-noise ratio in rodent models of dementia.

neuroscience↗