Alzheimer’s disease (AD) is an incurable neurodegenerative disease and the most common form of dementia, and AD and type II diabetes (DM II) are two of the most common diseases of aging. Numerous studies demonstrate DM II with increased risk for dementia, however, the mechanisms linking DM II and AD have not been fully elucidated. There is increasing evidence suggesting that cerebral vascular dysfunction plays an important role in the development of AD. T2DN rat is a DM II rat model that exhibits diabetic nephropathy. The present study examines whether aged T2DN rat is associated with cognitive impairment, and whether autoregulation of cerebral blood flow (CBF) is impaired that contributes to AD. The levels of glucose (422 ± 32 vs. 94 ± 3 mg/dL) and glycated hemoglobin (HbA
1c
, 11.5 ± 0.2 vs. 4.3 ± 0.1%) were higher in 12-18 months old T2DN than in age matched SD control rats. CBF rose by 137 ± 15% and 36 ± 5%, respectively, in T2DN and SD rats when MAP was increased from 100 to 180 mmHg. Aged T2DN rats exhibited BBB leakage and “AD” like cerebral vascular remodeling. The expression of Amyloid β 42 (Aβ
4
2
), p-tau (S416), GFAP and IL-1 beta were significantly higher in the brains of T2DN vs. SD rats. T2DN rats also exhibited learning and memory dysfunction as the short term (2-hour; T2DN 96 ± 12 vs. SD 13 ± 3 seconds) and long term (24-hour; T2DN 105 ± 15 vs. SD 8 ± 2 seconds) latency of escape were longer in an eight-arm water maze test, and spent less time in the target arm 48 hours after training (T2DN 3.4 ± 2.6 vs. SD 45.0 ± 1.7%). These findings indicate that T2DN is a new type II diabetic rat model. Elderly T2DN rat is associated with an impaired autoregulation of CBF, glial activation and inflammation which may contribute to the development of cognitive impairment and AD.
Sevoflurane Induces Exaggerated and Persistent Cognitive Decline in a Type II Diabetic Rat Model by Aggregating Hippocampal Inflammation
