Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice.

Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-ß (Aß) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aß plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aß levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice.

Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint. Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests. These antidepressant and nootropic effects of cotinine were associated with an increase in the synaptophysin expression, a commonly used marker of synaptic density, in the hippocampus as well as the prefrontal and entorhinal cortices of restrained mice. The beneficial effects of cotinine in preventing various consequences of chronic stress were underscored by the inhibition of the glycogen synthase kinase 3 ß in the hippocampus and prefrontal cortex. Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse.

Implementing a community-supported school-based influenza immunization program.

School-based influenza immunization programs are increasingly recognized as a key component of community-based efforts to control annual influenza epidemics. Computer modeling suggests that immunizing 70% of schoolchildren could protect an entire community from the flu. Most of the school-based influenza immunization programs described in the literature have had support from industry or federal grants. This article describes a program that used only community resources to administer live, attenuated influenza vaccine supplied by the state health department. Beginning in 2006, the Alachua County Health Department and school system, working in collaboration with the University of Florida, began exploration of a non-mandatory community-wide school-based influenza immunization program, with the goal of achieving high levels of immunization of the ~22,000 public and private pre-K through grade 8 students in the county. In 2009-10 the program was repeated. This report describes the procedures developed to achieve the goal, the barriers that were encountered, and solutions to problems that occurred during the implementation of the program. Preliminary data suggest that the crude immunization rate in the schools was approximately 55% and that at least 10% more students were immunized by their health providers. At an operational level, it is possible to achieve high immunization rates if the stakeholders share a common vision and there is extensive community involvement.