Biology subjects

Tadros, M. A.

Publications and source records attributed to Tadros, M. A..

3 recordsLinked to original sources

bioRxiv2024

Anatomical and functional studies of isolated vestibular neuroepithelia from Meniere's Disease patients

Surgical removal of vestibular end organs is a final treatment option for people with intractable Menieres Disease. We describe the use of surgically excised vestibular neuroepithelium from patients with Menieres Disease for 1) anatomical investigation of hair cell and nerve fibres markers using immunohistochemistry and 2) functional studies using electrophysiological recordings of voltage-activated currents. Our data shows considerable reduction in and disorganization of vestibular hair cells in the cristae ampullares while nerve fibres are in contact with remaining sensory receptors but appear thin in regions where hair cells are absent. Electrophysiological recordings of voltage-activated potassium currents from surviving hair cells demonstrate normal activity in both type I and type II vestibular hair cells. In addition, current-voltage plots from type I vestibular hair cells are consistent with the presence of a surrounding calyx afferent terminal. These data indicate surviving hair cells in Menieres Disease patients remain functional and capable of transmitting sensory information to the central nervous system. Determining functionality of vestibular receptors and nerves is critical for vestibular implant research to restore balance in people with Menieres Disease. Summary StatementThis study shows, that while there is significant hair cell loss in Menieres Disease patients, surviving type I and type II vestibular hair cells have normal voltage-activated conductances.

neuroscience↗

bioRxiv2023

Autonomic regions of the brainstem show a sex-specific inflammatory response to systemic neonatal lipopolysaccharide

Early life inflammation has been linked to long-term deficits in the central nervous system in relation to behavioural disorders, but it is now becoming more apparent it can also lead to autonomic dysfunction. The brainstem contains all critical control centres for autonomic homeostasis, so we used the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the autonomic regions of the brainstem. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with sacrifices made on postnatal days 7 and 90. At both timepoints inflammatory mediators were assessed in the brainstem via RT-qPCR and microglia were characterised by immunofluorescence in the autonomic regions of the brainstem. In the brainstem there was a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators at baseline. AT both ages, microglial morphology had a significant change to branch length and soma size in a sex-specific manner, which strongly indicate a significant effect of neonatal immune activation. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant impact on the brainstem in adulthood.

neuroscience↗

bioRxiv2023

Sex-specific developmental changes in spinal cord pain pathways following neonatal inflammation

Early-life inflammation can have long lasting impact on pain processing and pain behaviours. For example, we have shown neonatal inflammation can result in changes within spinal neuronal networks and altered flinching of the hind paw following formalin injection three weeks later. This suggests mechanisms for altered pain behaviours lie in first and second order neurons in the pain neuroaxis. Exactly how these changes progress during postnatal development is not known. Accordingly, we investigated neuroinflammatory markers in sensory neurons (dorsal root ganglia; DRGs) and spinal cords of Wistar rats (both sexes) after early life inflammation. Rats were injected with LPS or saline on postnatal days (P) 3 and 5. DRGs and spinal cords (SC) were isolated on P7, 13 and 21, and the expression of six inflammatory mediators were quantified via RT-qPCR. In the DRG, four proinflammatory mediators were elevated in P7 rats exposed to LPS. By P13, only two proinflammatory agents were elevated, whereas at P21 the levels of all six inflammatory mediators were similar between LPS and saline-treated rats. There were no sex-specific differences in the expression profile of any mediator in DRGs. In the spinal cord this expression profile was reversed with no change in inflammatory mediators at P7, elevation of two at P13 and four at P21 in LPS treated rats. Interestingly, these differences were greater in the spinal cords of female rats, indicating sex-specific modulation of neuroinflammation even at these early stages of postnatal development. The increased inflammatory mediator profile in the spinal cords of P21 LPS-treated rats was accompanied by sex-specific modulation of astrocytic (GFAP) activation, with females showing an increase and males a decrease in GFAP following LPS exposure. Together, these data indicate sensory neurons are more susceptible to acute inflammation whereas inflammation in the spinal cord is delayed. The sex-specific modulation of inflammation during critical phases of development may help explain altered pain behaviours in adult males and females.

neuroscience↗