Search bioRxiv⌕ Search

Biology subjects

Krishnamoorthy, R.

Publications and source records attributed to Krishnamoorthy, R..

2 recordsLinked to original sources

Changes in peripheral sensory afference do not alter predictive motor planning: evidence from carpal tunnel syndrome

Anticipatory control organises motor output prior to predictable perturbations and is expressed in multi-digit tasks as anticipatory synergy adjustments (ASAs), which coordinate digit forces before movement onset. Whether such feedforward coordination depends on peripheral sensory input remains unclear. Carpal tunnel syndrome provides a model of altered median nerve afference with within-subject restoration following surgical decompression. We quantified ASA onset and amplitude in eleven individuals with carpal tunnel syndrome performing a multi-finger grasp-and-release task before and three weeks after decompression surgery. Postoperatively, sensory function improved, and total grip force decreased significantly across task phases, indicating more efficient force regulation. In contrast, ASA onset timing and amplitude were unchanged. Equivalence testing confirmed that pre- and post-operative ASA measures fell within predefined bounds of practical equivalence. These findings demonstrate a central-peripheral dissociation: feedback-mediated grip force scaling is sensory-dependent and rapidly recalibrates following afferent restoration, whereas feedforward synergy coordination remains stable despite months of degraded peripheral input. The preserved ASA suggests that central motor planning circuits maintain anticipatory coordination through efferent copy or cerebellar-mediated internal models that do not require continuous peripheral recalibration. This resilience may reflect the brains ability to maintain predictive motor planning despite chronic sensory degradation, with implications for understanding compensatory mechanisms in peripheral neuropathies and the limits of sensory-dependent motor adaptation.

neuroscience↗

Amyloid beta aggregation promoted by iron leads to neuronal loss in an ex vivo model of Alzheimer's disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta (A{beta}) plaques and neurofibrillary tangles. Despite well-established iron accumulation in the AD brain, its role in exacerbating A{beta} toxicity is often overlooked in therapeutic research. We developed a 3D ex vivo organotypic brain slice cultures (OBSC) with A{beta} monomers and ferric citrate to mimic A{beta} deposits and iron overload to investigate the impact of excess iron on A{beta} toxicity in pig and human brains. Light and electron microscopy, biochemical assays, and multiple regression modeling were employed to assess iron-mediated A{beta} toxicity in neurons and glial cells. We show that OBSC offer a close approximation of in vivo morphological and physiological properties and can retain both neurons and glial cells for extended periods, and respond to experimental manipulations. We show that iron promotes A{beta} fibrillization into long fibrils, with this process further influenced by temperature. A{beta} selectively accumulated in neurons, leading to their death, sparing glial cells. In contrast, Iron, though generally toxic to neurons, exhibited unspecific cytotoxicity. Notably, the combined presence of A{beta} and iron synergistically increased neuronal death while reducing glial cell loss. Correlation analysis revealed that this synergic interaction enhances the toxicity of each other in a mutual fashion - A{beta} directs the neuronal toxicity while iron promotes A{beta} fibrillization, leading to targeted neuronal loss. In conclusion, our findings emphasize the critical role of excess iron and A{beta} in driving neuronal death in AD, underlining the importance of targeting iron accumulation along with A{beta} clearance but also addressing in future AD therapies, while also supporting our OBSC model as a valuable platform for studying the same.

neuroscience↗