The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 μg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes. The Morris water maze (MWM) was used to assess the spatial learning and memory. Liraglutide decreased levels of hyperphosphorylated tau and NFs in 3 × Tg liraglutide-treated (Tg + LIR) mice, increased ERK phosphorylation, and decreased JNK phosphorylation. Liraglutide also decreased the number of degenerative neurons in the hippocampus and cortex of Tg + LIR mice, and shortened their escape latencies and increased their hidden platform crossings in the MWM task. Liraglutide did not significantly affect the animals' body weight (BW) or fasting blood glucose. Liraglutide can reduce hyperphosphorylation of tau and NFs and reduce neuronal degeneration, apparently through alterations in JNK and ERK signaling, which may be related to its positive effects on AD-like learning and memory impairment.

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Background: Most cetaceans inhabit the hyperosmotic marine environment with only a few species living in freshwater habitats. The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) is the only freshwater subspecies of the genus. Our aim was to study whether the osmoregulation mechanism of the Yangtze finless porpoise is different from the marine subspecies, the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri). We assayed and compared the concentrations of the constituents involved in osmoregulation in the blood and urine in the Yangtze finless porpoise and the East Asian finless porpoise. We also compared the corresponding urine constituents of the porpoises with existing data on fin whales (Balaenoptera physalus) and bottlenose dolphins (Tursiops truncatus). Results: The mean plasma osmolality of Yangtze finless porpoise was significantly lower than that of the marine subspecies (P < 0.01). Similarly, the urine osmolality of Yangtze finless porpoise was also significantly lower than that of its marine counterpart (P < 0.05). However, the urine sodium concentration of freshwater finless porpoise was significantly lower than that in the marine subspecies (P < 0.01), even though their serum sodium has no significant difference. Moreover, the freshwater porpoise has significantly lower urine urea concentration but much higher serum urea than in the marine finless porpoise (P < 0.05). Conclusions: These results suggest that the freshwater finless porpoise does have different osmoregulatory mechanism from marine cetaceans. Conserving sodium by excreting urine with low ion levels may be an essential strategy to maintain the serum electrolyte balance for the freshwater subspecies that also appears to be more susceptible to hyponatremia.