Niemann Pick disease type C1 (NPC) is an autosomal recessive disease characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities to ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage. This transplantation resulted in the recovery of motor function in the Rota Rod test and impaired cholesterol homeostasis leading to increased levels of cholesterol efflux-related genes such as LXRα, ABCA1, and ABCG5 while decreased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase were observed in NPC mice. In the cerebrum, hUCB-MSCs enhanced neuronal cell survival and proliferation, where they directly differentiated into electrically active MAP2-positive neurons as demonstrated by whole-cell patch clamping. In addition, we observed that hUCB-MSCs reduced Purkinje neuronal loss by suppression of inflammatory and apoptotic signaling in the cerebellum as shown by immunohistochemistry. We further investigated how hUCB-MSCs enhance cellular survival and inhibit apoptosis in NPC mice. Neuronal cell survival was associated with increased PI3K/AKT and JAK2/STAT3 signaling; moreover, hUCB-MSCs modulated the levels of GABA/glutamate transporters such as GAT1, EAAT2, EAAT3, and GAD6 in NPC mice as assessed by Western blot analysis. Taken together, our findings suggest that hUCB-MSCs might play multifunctional roles in neuronal cell survival and ameliorating motor deficits of NPC mice.

In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes, on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to 14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and neuroblast differentiation in the SZDG in diabetic rats.

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As the health care system continues to evolve, there will be a shift in the care that physicians are asked to provide: from high-tech to patient-centered, from treatment-focused to prevention-focused. To improve the health of communities, health providers need to apply skills beyond those contained in the traditional biomedical model and must strive to encompass the community-based public health model.Physicians must function effectively within a multidisciplinary team in order to provide optimal health care in a setting of complex needs which far exceed the capacity of any one health discipline to address adequately. Students need first hand experience working with population issues in all learning settings -the hospital, the clinic and the community -to stimulate their interest in a population perspective. The medical education community needs to search for innovative, creative approaches to help the students develop the knowledge skills, and attitudes to practice.Community-oriented primary care (COPC) addresses the need to train practitioners in primary care practice that is community-responsive and that includes a public health perspective. It helps bridge the gap between academic medicine and the community it is designed to serve while fostering linkages among providers and community groups. It provides the structure for the various members of a public health team, often isolated from one another within their own institutions, to share ideas that focus on the need for integrity and simplicity in a community-3) * 교신저자: 이윤환, 아주대학교 의과대학 예방의학교실 지역사회중심의 일차의료(Community-Oriented Primary Care): 미국의 미래지향적인 의학교육 -330 -responsive health care system. But perhaps most importantly, it restores the social contract between medicine and society.

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