Biology subjects

Eyre, B.

Publications and source records attributed to Eyre, B..

6 recordsLinked to original sources

bioRxiv2024

Characterizing vascular function in mouse models of Alzheimer's disease, atherosclerosis, and mixed Alzheimer's and atherosclerosis

SignificanceAlzheimers disease does not occur in isolation and there are many comorbidities associated with the disease - especially diseases of the vasculature. Atherosclerosis is a known risk factor for the subsequent development of Alzheimers disease, therefore understanding how both diseases interact will provide a greater understanding of co-morbid disease progression and aid the development of potential new treatments. AimThe current study characterizes hemodynamic responses and cognitive performance in APP/PS1 Alzheimers mice, atherosclerosis mice, and a mixed disease group (APP/PS1 & atherosclerosis) between the ages of 9 and 12 months. ApproachWhisker-evoked hemodynamic responses and recognition memory were assessed in awake mice, immunohistochemistry to assess amyloid pathology, and histology to characterize atherosclerotic plaque load. ResultsWe observed hemodynamic deficits in atherosclerosis mice (vs Alzheimers, mixed disease or wild-type mice), with reduced short-duration stimulus-evoked hemodynamic responses occurring when there was no concurrent locomotion during the stimulation period. Mixed Alzheimers and atherosclerosis models did not show differences in amyloid beta coverage in the cortex or hippocampus or atherosclerotic plaque burden in the aortic arch vs relevant Alzheimers or atherosclerosis controls. Consistent with the subtle vascular deficits and no pathology differences, we also observed no difference in performance on the novel object recognition task across groups. ConclusionsThese results emphasize the importance of experimental design for characterizing vascular function across disease groups, as locomotion and stimulus duration impacted the ability to detect differences between groups. Whilst atherosclerosis did reduce hemodynamic responses, these were recovered in the presence of co-occurring Alzheimers disease which may provide targets for future studies to explore the potentially contrasting vasodilatory mechanisms these diseases impact.

neuroscience↗

bioRxiv2024

Voluntary locomotion induces an early and remote hemodynamic decrease in the large cerebral veins

SignificanceBehavior regulates dural and cerebral vessels, with spontaneous locomotion inducing dural vessel constriction and increasing stimulus-evoked cerebral hemodynamic responses. It is vital to investigate the function of different vascular network components, surrounding and within the brain, to better understand the role of the neurovascular unit in health and neurodegeneration. AimWe characterized locomotion-induced hemodynamic responses across vascular compartments of the whisker barrel cortex: artery, vein, parenchyma, draining and meningeal vein. ApproachUsing 2D-OIS, hemodynamic responses during locomotion were recorded in 9-12-month-old awake mice: wild-type, Alzheimers disease (AD), atherosclerosis or mixed (atherosclerosis/AD) models. Within somatosensory cortex, responses were taken from pial vessels inside the whisker barrel region ([WBR]: "whisker artery" and "whisker vein"), a large vein from the sagittal sinus adjacent to the WBR (draining vein), and meningeal vessels from the dura mater (which do not penetrate cortical tissue). ResultsWe demonstrate that locomotion evokes an initial decrease in total hemoglobin (HbT) within the draining vein before the increase in HbT within WBR vessels. The locomotion event size influences the magnitude of the HbT increase in the pial vessels of the WBR, but not of the early HbT decrease within the draining veins. Following locomotion onset, an early HbT decrease was also observed in the overlying meningeal vessels, which unlike within the cortex did not go on to exceed baseline HbT levels during the remainder of the locomotion response. We show that locomotion-induced hemodynamic responses are altered in disease in the draining vein and whisker artery, suggesting this could be an important neurodegeneration biomarker. ConclusionThis initial reduction in HbT within the draining and meningeal veins potentially serves as a space saving mechanism, allowing for large increases in cortical HbT associated with locomotion. Given this mechanism is impacted by disease it may provide an important target for vascular-based therapeutic interventions.

neuroscience↗

bioRxiv2022

Bidirectional alterations in brain temperature profoundly modulate spatiotemporal neurovascular responses in-vivo: Implications for theragnostics

Neurovascular coupling (NVC) is a mechanism that, amongst other known and latent critical functions, ensures activated brain regions are adequately supplied with oxygen and glucose. This biological phenomenon underpins non-invasive perfusion-related neuroimaging techniques and recent reports have implicated NVC impairment in several neurodegenerative disorders. Yet, much remains unknown regarding NVC in health and disease, and only recently has there been burgeoning recognition of a close interplay with brain thermodynamics. Accordingly, we developed a novel multi-modal approach to systematically modulate cortical temperature and interrogate the spatiotemporal dynamics of sensory-evoked NVC. We show that changes in cortical temperature profoundly and intricately modulate NVC, with low temperatures associated with diminished oxygen delivery, and high temperatures inducing a distinct vascular oscillation. These observations provide novel insights into the relationship between NVC and brain thermodynamics, with important implications for brain-temperature related therapies, functional biomarkers of elevated brain temperature, and in-vivo methods to study neurovascular coupling.

neuroscience↗

bioRxiv2021

The effects of locomotion on sensory-evoked haemodynamic responses in the cortex of awake mice

Investigating neurovascular coupling in awake rodents is becoming ever more popular due, in part, to our increasing knowledge of the profound impacts that anaesthesia can have upon brain physiology. Although awake imaging brings with it many advantages, we still do not fully understand how voluntary locomotion during imaging affects sensory-evoked haemodynamic responses. In this study we investigated how evoked haemodynamic responses can be affected by the amount and timing of locomotion. Using an awake imaging set up, we used 2D-Optical Imaging Spectroscopy (2D-OIS) to measure changes in cerebral haemodynamics within the sensory cortex of the brain during either 2s whisker stimulation or spontaneous (no whisker stimulation) experiments, whilst animals could walk on a spherical treadmill. We show that locomotion alters haemodynamic responses. The amount and timing of locomotion relative to whisker stimulation is important, and can significantly impact sensory-evoked haemodynamic responses. If locomotion occurred before or during whisker stimulation, the amplitude of the stimulus-evoked haemodynamic response was significantly altered. Therefore, monitoring of locomotion during awake imaging is necessary to ensure that conclusions based on comparisons of evoked haemodynamic responses (e.g., between control and disease groups) are not confounded by the effects of locomotion.

neuroscience↗

bioRxiv2020

Assessment of Neurovascular Coupling & Cortical Spreading Depression in Mixed Models of Atherosclerosis & Alzheimer's Disease

Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in preparations that modelled Alzheimers disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9-12m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, levels of oxyhaemoglobin & deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3x fold increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimers-related amyloid-plaques.

neuroscience↗

bioRxiv2019

Seasonal and spatial controls on N2O concentrations and emissions in low-nitrogen estuaries: Evidence from three tropical systems

Estuarine N2O emissions contribute to the atmospheric N2O budget, but little is known about estuary N2O fluxes under low dissolved inorganic nitrogen (DIN) conditions. We present high-resolution spatial surveys of N2O concentrations and water-air fluxes in three low-DIN (NO3 - < 30 {micro}mol L-1) tropical estuaries in Queensland, Australia (Johnstone River, Fitzroy River, Constant Creek) during consecutive wet and dry seasons. Constant Creek had the lowest concentrations of dissolved inorganic nitrogen (DIN; 0.01 to 5.4 {micro}mol L-1 of NO3 - and 0.09 to 13.6 {micro}mol L-1 of NH4+) and N2O (93-132% saturation), and associated lowest N2O emissions (- 1.4 to 8.4 {micro}mol m-2 d-1) in both seasons. The other two estuaries exhibited higher DIN inputs and higher N2O emissions. The Johnstone River Estuary had the highest N2O concentrations (97-245% saturation) and emissions (- 0.03 to 25.7 {micro}mol m-2 d-1), driven by groundwater inputs from upstream sources, with increased N2O input in the wet season. In the Fitzroy River Estuary, N2O concentrations (100-204% saturation) and emissions (0.03-19.5 {micro}mol m-2 d-1) were associated with wastewater inputs, which had a larger effect during the dry season and were diluted during the wet season. Overall N2O emissions from the three tropical estuaries were low compared to previous studies, and at times water-air N2O fluxes were actually negative, indicating that N2O consumption occurred. Low water column NO3 - concentration (i.e. < 5 {micro}mol L-1) appears to promote negative water-air N2O fluxes in estuary environments; considering the number of estuaries and mangrove creeks where DIN falls below this threshold, negative water-air N2O fluxes are likely common.

biochemistry↗