Diabetes increases the risk of Alzheimer’s disease (AD). The pathological hallmarks for AD brains are extracellular amyloid plaques formed by β-amyloid peptide (Aβ) and intracellular neurofibrillary tangles consisting of hyperphosphorylated tau protein. This study was designed to determine AD-like brain changes in mice modeling for type 2 diabetes. The effects of metformin on these changes also were studied. Seven-week old male db/db mice received intraperitoneal injection of 200 mg kg−1 d−1 metformin for 18 weeks. They were subjected to Barnes maze at an age of 21 weeks and fear conditioning at an age of 24 weeks to assess their cognitive functions. Hippocampus was harvested after these tests for biochemical evaluation. The db/db mice had more tau phosphorylated at S396 and total tau in their hippocampi than their non-diabetic control db+ mice. Activated/phosphorylated c-jun N-terminal kinase (JNK), a tau kinase, was increased in the db/db mouse hippocampus. Metformin attenuated the increase of total tau, phospho-tau and activated JNK. The db/db mice had increased Aβ levels. Metformin attenuated the reduction of synaptophysin, a synaptic protein, in the db/db mouse hippocampus. Metformin did not attenuate the impairments of spatial learning and memory as well as long-term hyperglycemia in the db/db mice. Our results suggest that the db/db mice have multiple AD-like brain changes including impaired cognitive functions, increased phospho-tau and Aβ as well as decreased synaptic proteins. Activation of JNK may contribute to the increased phospho-tau in the db/db mice. Metformin attenuates AD-like biochemical changes in the brain of these mice.

Patients undergoing elective THR under neuraxial anesthesia seem to have better outcomes than those under GA.

Post-operative cognitive dysfunction (POCD) is a clinical phenomenon characterized with cognitive decline in patients after anesthesia and surgery. It has been shown that interleukin-1β (IL-1β) contributes to the cognitive impairment of mice after surgery and isoflurane anesthesia. This study is designed to determine whether isoflurane alone increases inflammatory cytokines and causes cell injury and cognitive impairment. Four-month-old male Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Two weeks later, rats were subjected to Barnes maze and fear conditioning tests. Although animals exposed to or non-exposed to isoflurane developed spatial learning, animals exposed to isoflurane had significant impairments in long-term spatial memory assessed by Barnes maze. They also had impaired hippocampus-dependent learning and memory in fear conditioning test. IL-1β in the hippocampus was increased at 6 h after isoflurane exposure. Isoflurane also increased activated caspase 3 in the hippocampus and decreased the neuronal density in the CA1 region. However, isoflurane did not change the amount of β-amyloid peptide in the cerebral cortex at 29 days after isoflurane exposure when cognitive impairment was present. These results suggest that isoflurane increases inflammatory cytokine expression and causes cell injury in the hippocampus, which may contribute to isoflurane-induced cognitive impairment in rats.