Biology subjects

Rafiq, A. M.

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

3 recordsLinked to original sources

bioRxiv2026

UP-REGULATION OF SYNAPTOBREVIN-2 TO DELAY AGE-RELATED COGNITIVE IMPAIRMENT

The slowing of executive function and memory impairment are the leading hallmarks of cognitive decline with age. The exact cause of this change is unknown and is the focus of aging research. Expression levels of Vesicle Associated Membrane Protein 2 (VAMP2)/Synaptobrevin-2 (syb2) are decreased with age. Here we report results from a novel transgenic mouse model (TgV2) that overexpresses syb2. We hypothesized that overexpression of syb2 improves synaptic function during aging, thus it delays dementia. Aged TgV2 mice, which maintained syb2 levels, performed better in spatial memory tests than 2-year-old WT control mice, which had lost half of syb2 due aging. In hippocampal CA1 synapses of aged TgV2 mice, long-term potentiation was increased. These effects of maintained syb2 levels were beneficial for both males and females providing improved synaptic plasticity. These results indicate that overexpression of syb2 supports cognitive function throughout the aging process and better resist age-related synaptic dysfunction.

neuroscience↗

bioRxiv2024

Altered Copper Transport in Oxidative Stress-Dependent Brain Endothelial Barrier Dysfunction Associated with Alzheimer's Disease

Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimers Disease (AD), which is characterized by beta-amyloid (A{beta}) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in A{beta}42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A and/or ATP7B were downregulated in the hippocampus of AD mouse models, and in A{beta}42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, A{beta}42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function in hBMEC (measured by transendothelial electrical resistance), and tyrosine phosphorylation of VE-cadherin were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that A{beta}42 promotes ROS-dependent brain endothelial barrier dysfunction and VE-Cadherin phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD. HighlightsO_LIUpregulation of the Cu importer CTR1 and downregulation of the Cu exporter ATP7A in the hippocampus of AD mouse models C_LIO_LIA{beta}42 increases CTR1 expression while reduces ATP7A and ATP7B levels in human brain microvascular ECs. C_LIO_LIA{beta}42 triggers increased reactive oxygen species (ROS) production in human brain microvascular ECs through a CTR1- and Cu-dependent manner. C_LIO_LIA{beta}42 induces endothelial barrier dysfunction in human brain microvascular ECs through a CTR1-Cu-ROS-pendent manner. C_LI

neuroscience↗

bioRxiv2018

Temperate grass allergy season defined by spatio-temporal shifts in airborne pollen communities

Grass pollen is the worlds most harmful outdoor aeroallergen and sensitivity varies between species. Different species of grass flower at different times, but it is not known how airborne communities of grass pollen change in time and space. Persistence and high mobility of grass pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass pollen does not persist for an extended time in the air, shifting pollen communities would be predicted throughout the summer months. Here, using targeted high throughput sequencing, we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, throughout the grass allergy season. All grass genera displayed discrete, temporally restricted peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition of grass pollen exposure changes substantially across the allergy season. By developing more refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-economic benefits.

ecology↗