Timing and Duration of Prediabetic Metabolic Dysfunction Differentially Impact Cerebral Perfusion, Vascular...

Area of Science:

• Neuroscience
• Metabolic Research
• Vascular Biology

Background:

• Obesity is a significant risk factor for metabolic dysfunction and cognitive decline.
• The impact of obesity's age of onset and sex on neurovascular health is not well understood.

Purpose of the Study:

• To investigate how the timing and duration of diet-induced obesity affect metabolism, cognition, and cerebrovascular perfusion in male and female mice.
• To identify potential vascular mechanisms linking early metabolic stress to cognitive impairment.

Main Methods:

• Induction of diet-induced obesity in mice using a high-fat diet.
• Assessment of body weight, glucose regulation, recognition memory, and spatial working memory.
• Analysis of cerebrovascular perfusion, cortical blood flow, and hippocampal vascular complexity (branch points, vessel diameter).

Main Results:

• High-fat diet increased body weight and impaired glucose regulation, more so in females.
• Obesity selectively impaired recognition memory but not spatial working memory.
• Early-life obesity led to reduced cortical perfusion and decreased hippocampal vascular complexity, correlating with memory deficits.

Conclusions:

• Early-life obesity represents a critical window of vulnerability for developing long-term neurovascular and cognitive dysfunction.
• Vascular alterations, particularly in the hippocampus, may mediate the link between early metabolic stress and cognitive impairment.