Biology subjects

Khan, H. F.

Publications and source records attributed to Khan, H. F..

3 recordsLinked to original sources

bioRxiv2025

An integrative framework linking molecular signatures and locomotory phenotypes in space-induced sarcopenia

Age-related skeletal muscle deterioration, referred to as sarcopenia, poses significant risks to astronaut health and mission success during spaceflight, yet its multisystem drivers remain poorly understood. While terrestrial sarcopenia manifests gradually through aging, spaceflight induces analogous musculoskeletal decline within weeks, providing an accelerated model to study conserved atrophy mechanisms. Here, we introduced an integrative framework combining cross-species genetic analysis with physiological modeling to understand mechanistic pathways in space-induced sarcopenia. By analyzing rodent and human datasets, we identified conserved molecular pathways underlying microgravity-induced muscle atrophy, revealing shared regulators of neuromuscular signaling including pathways related to neurotransmitter release and regulation, mitochondrial function, and synaptic integration. Building upon these molecular insights, we developed a physiologically grounded central pattern generator model that reproduced spaceflight-induced locomotion deficits in mice. This multi-scale approach established mechanistic connections between transcriptional changes and impaired movement kinetics while identifying potential therapeutic targets applicable to both spaceflight and terrestrial aging-related muscle loss.

systems biology↗

bioRxiv2025

Synaptic phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein aggregation

Cortical dysfunction is increasingly recognized as a major contributor to the non-motor symptoms associated with Parkinsons disease (PD) and other synucleinopathies. Although functional alterations in cortical circuits have been observed in preclinical PD models, the underlying molecular mechanisms are unclear. To bridge this knowledge gap, we investigated tissue-level changes in the cortex of rats and mice treated with alpha-synuclein (aSyn) seeds using a multi-omics approach. Our study revealed significant phosphoproteomic changes, but not global proteomic or lipid profiling changes, in the rat sensorimotor cortex 3 months after intra-striatal injection with aSyn preformed fibrils (PFFs). Gene ontology analysis of the phosphoproteomic data revealed that PFF administration impacted pathways related to synaptic transmission and cytoskeletal organization. Similar phosphoproteomic perturbations were observed in the sensorimotor cortex of mice injected intrastriatally or intracortically with aSyn PFFs. Functional analyses demonstrated increased neuronal firing rates and enhanced spike-spike coherence in the sensorimotor cortex of PFF-treated mice, suggesting that aSyn seeds induced cortical circuit dysfunction. Bioinformatics analysis of the altered phosphosites indicated the involvement of several kinases, including casein kinase-2 (CK2) and Protein Kinase A (PKA). Enrichment of kinase-activating pT/pY MAPK (ERK) phosphosites revealed apparent engagement of the ERK signaling cascade and led to the identification of pERK1/2-positive intraneuronal granulovacuolar body (GVB)-like structures specifically in aggregate-bearing neurons. Collectively, these findings highlight the importance of phosphorylation-mediated signaling pathways in the cortical response to aSyn pathology spread in PD and related synucleinopathies, setting the stage for developing new therapeutic strategies.

neuroscience↗

bioRxiv2024

A TRANSLAMINAR SPACETIME CODE SUPPORTS TOUCH-EVOKED TRAVELING WAVES

Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we performed simultaneous electrophysiology and two-photon calcium imaging through transparent NeuroGrids and mapped touch-evoked cortical traveling waves and their underlying microcircuit dynamics. In awake mice, both passive and active whisker touch elicited traveling waves within and across barrels, with a fast early component followed by a variable late wave that lasted hundreds of milliseconds post-stimulus. Strikingly, late-wave dynamics were modulated by stimulus value and correlated with task performance. Mechanistically, the late wave component was i) modulated by motor feedback, ii) complemented by a sparse ensemble pattern across layer 2/3, which a balanced-state network model reconciled via inhibitory stabilization, and iii) aligned to regenerative Layer-5 apical dendritic Ca2+ events. Our results reveal a translaminar spacetime pattern organized by cortical feedback in the sensory cortex that supports touch-evoked traveling waves. GRAPHICAL ABSTRACT AND HIGHLIGHTS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/593381v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@c98840org.highwire.dtl.DTLVardef@1105364org.highwire.dtl.DTLVardef@d2f2c9org.highwire.dtl.DTLVardef@1418744_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIWhisker touch evokes both early- and late-traveling waves in the barrel cortex over 100s of milliseconds C_LIO_LIReward reinforcement modulates wave dynamics C_LIO_LILate wave emergence coincides with network sparsity in L23 and time-locked L5 dendritic Ca2+ spikes C_LIO_LIExperimental and computational results link motor feedback to distinct translaminar spacetime patterns C_LI

neuroscience↗