Biology subjects

Ghasemlou, N.

Publications and source records attributed to Ghasemlou, N..

4 recordsLinked to original sources

bioRxiv2026

Disease progression shapes circadian and locomotor disruption in a model of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system featuring a wide range of debilitating symptoms. Wearable activity recording devices have recently been adopted to improve symptom monitoring in MS, capturing symptoms related to sleep/wake cycles, circadian disruption, and fatigue. However, comparable measures of activity have yet been established in pre-clinical models of MS, the most widely used being experimental autoimmune encephalomyelitis (EAE). We therefore sought to characterize changes in continual home-cage activity over the course of EAE, and establish whether home-cage monitoring can be used as an observer-independent measure of disease progression. Our results showed that locomotor activity in the mid-active/dark phase was most severely affected by EAE. Disrupted circadian (24-hour) activity was observed during the peak and onset stages of disease. Bout activity analysis revealed >40-minute long activity bouts as a sensitive indicator of non-motor symptoms independent of clinical score-based motor deficits. Current assessment of disease progression in EAE relies on clinical scores, which primarily assess motor deficits through visual observation prone to observer bias. Various computed activity parameters were found to be altered during key disease stages, suggesting that a combination of activity measures can serve as objective indicators of disease progression. Overall, our results show that home-cage activity effectively captures signs of non-motor symptoms in the EAE model of MS and can serve as an observer-independent measure of EAE disease progression.

animal behavior and cognition↗

bioRxiv2025

Nociceptor clock genes control excitability and pain perception in a sex- and time-dependent manner

Nociception is critical for pain perception and survival and begins with the activation of nociceptors, specialized sensory neurons located in the dorsal root ganglia (DRGs). Both sex and circadian rhythms, governed by clock genes, seem to play a significant role in modulating pain perception. However, the potential interaction between circadian rhythms and sex differences in nociception at the peripheral level has been largely overlooked. Here, we first report that DRGs from mice express clock genes in a time- and sex-dependent manner. Using whole-cell recordings in whole-mounted DRGs and optogenetic stimulation of Nav1.8-expressing neurons, we demonstrate that male nociceptors exhibit reduced excitability during the night, while female nociceptor excitability remains stable across time points. Disruption of the core clock gene Bmal1 in Nav1.8-expressing neurons not only diminished nociceptor activity but also abolished the nighttime reduction in heat sensitivity, highlighting a pivotal role for the molecular clock in regulating nociception. Transcriptomic analyses, voltage-clamp recordings, and pharmacological experiments identified the voltage-gated chloride channel ClC-2, controlled by Bmal1, as a key mediator for the observed fluctuations in male nociceptor excitability. This work opens new avenues for chronobiology-inspired strategies in pain management tailored to sex-specific mechanisms.

neuroscience↗

bioRxiv2024

Chronobiological rhythms control of site- and cell-specific miRNA and mRNA genes and networks across the central nervous system

Biological rhythms control gene expression, but effects on central nervous system (CNS) cells and structures remain undefined. While circadian (24-hour) rhythms are most studied, many genes have periods of greater and less than 24-hours; these fluctuations can be both site- and cell-specific. Identifying patterns of gene rhythmicity across the CNS is necessary for both the study of chronobiology and to make sense of data obtained in the laboratory. We now identify cycling mRNAs, miRNAs, gene networks and novel mRNA-miRNA co-expression pairs in the cortex, hypothalamus, and corpus striatum using high-dimensional datasets. A searchable catalogue (https://www.ghasemloulab.ca/chronoCNS) was created to help refine the analysis of cellular/molecular rhythmicity across the CNS. Immunofluorescence was also used to confirm the rhythmicity of key targets across cells in these structures, with strong cycling signatures in resting oligodendrocytes. Our study sheds light on the contribution of circadian, ultradian, and infradian rhythms and mRNA-miRNA interactions to CNS function.

neuroscience↗

bioRxiv2018

γδ T cells do not contribute to peripheral inflammatory pain

Circulating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are {gamma}{delta} T cells, which serve important roles in infection and disease. Using a transgenic mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of inflammatory pain were used: intraplantar injection of formalin and incisional wound (as models of acute inflammatory pain) and intraplantar injection of complete Freunds adjuvant (as a model of chronic inflammatory pain). Our results show that absence of these cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that {gamma}{delta} T cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.

neuroscience↗