Sex differences in the effects of high fat diet on underlying neuropathology in a mouse model of VCID.

BACKGROUND: Damage to the cerebral vasculature can lead to vascular contributions to cognitive impairment and dementia (VCID). A reduction in blood flow to the brain leads to neuropathology, including neuroinflammation and white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is a risk factor for VCID which may be sex-dependent (female bias). METHODS: We compared the effects of mid-life metabolic disease between males and females in a chronic cerebral hypoperfusion mouse model of VCID. C57BL/6J mice were fed a control or high fat (HF) diet starting at ~ 8.5 months of age. Three months after diet initiation, sham or unilateral carotid artery occlusion surgery (VCID model) was performed. Three months later, mice underwent behavior testing and brains were collected to assess pathology. RESULTS: We have previously shown that in this VCID model, HF diet causes greater metabolic impairment and a wider array of cognitive deficits in females compared to males. Here, we report on sex differences in the underlying neuropathology, specifically white matter changes and neuroinflammation in several areas of the brain. White matter was negatively impacted by VCID in males and HF diet in females, with greater metabolic impairment correlating with less myelin markers in females only. High fat diet led to an increase in microglia activation in males but not in females. Further, HF diet led to a decrease in proinflammatory cytokines and pro-resolving mediator mRNA expression in females but not males. CONCLUSIONS: The current study adds to our understanding of sex differences in underlying neuropathology of VCID in the presence of a common risk factor (obesity/prediabetes). This information is crucial for the development of effective, sex-specific therapeutic interventions for VCID.

Reduced blood flow to the brain resulting from damaged blood vessels can lead to vascular dementia. Neuroinflammation and white matter damage are characteristics of vascular dementia. Middle-age is a time when obesity and prediabetes can increase risk for vascular dementia. This increase in risk is greater for women. A high fat diet causes obesity and prediabetes in mice. We compared the effects of diet-induced obesity in middle-age between males and females in a mouse model of vascular dementia. We have previously shown that a high fat diet causes greater obesity and prediabetes and a wider array of learning and memory problems in females compared to males. Here, we report on sex differences in the damage to the brain. White matter was negatively impacted by vascular dementia in males and high fat diet in females, with more severe prediabetes correlating with less white matter markers in females only. High fat diet led to an increase in activation of microglia (immune cells in the brain) in males but not in females. High fat diet also led to a decrease in pro-inflammatory and pro-resolving mediators expression in females but not males. The current study adds to our understanding of sex differences in underlying damage to the brain caused by vascular dementia in the presence of common risk factors (obesity and prediabetes). This information is needed for the development of effective, sex-specific treatments for vascular dementia.

Longitudinal trends in asthma emergency department visits, pollutant and pollen levels, and weather variables in the Bronx from 2001-2008.

Objective: To evaluate how asthma-related emergency department visits (AREDV), air pollutant levels, pollen counts, and weather variables changed from 2001 to 2008 in the Bronx, NY. Methods: 42,065 daily AREDV values (1 January 2001 to 31 December 2008) were collected using our institution's Clinical Looking Glass software. Daily values of sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), temperature, and humidity were obtained from the National Climatic Data Center's Bronx station. Daily tree pollen counts were obtained from the Armonk counting station near the Bronx. Median values for each variable were analyzed using the Mann-Whitney test to compare 2001-2004 and 2005-2008 values. Simple linear regression examined associations between AREDV and individual pollutants. Due to seasonal variations of the variables, each season was considered separately. Results: There were significant decreases for AREDV, SO2, CO, and humidity for all seasons, and for NO2 in the spring and winter. Significant increases occurred for O3 in the spring, fall, and winter; for temperature in the summer and winter; and for tree pollen in the spring. Significant positive associations were found between AREDV and SO2, CO, NO2, and humidity, respectively, while significant negative associations were found between AREDV and O3 and temperature, respectively. Conclusions: From 2001 to 2008, significant: a) decreases in AREDV, SO2, CO, and humidity for all seasons, and decreases in NO2 for the spring and winter; and b) increases in O3, temperature, and spring tree pollen were observed. By tracking and anticipating environmental and pollutant changes, efforts can be made to minimize AREDV.