ABSTRACT
Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.
ABSTRACT
BACKGROUND: The regeneration and repair of skeletal muscle after injury relies on the new nucleus formed through muscle satellite cell proliferation. However, there are few reports on the relationship between the skeletal muscle cell proliferation and the vimentin expression.OBJECTIVE: To explore the relationship between the skeletal muscle cell proliferation and the vimentin expression, as well as the mechanism underlying the repair of exercise-induced skeletal muscle micro-injury. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was done at the Sports Human Science Experimental Center in Hunan Normal University between December 2007 and September 2008. MATERIALS: A total of 50 male SD rats, aged 8 weeks, were randomly divided into a control group and a training group which were subdivided in to four groups at the time points of immediate post-exercise, hour 3, hour 24 and hour 48 post-exercise, with 10 ones in each of the five groups.METHODS: Rats in the training group underwent 3 days of repetitive exhausting eccentric exercise on a treadmill of-16° slope at the speed of 16 m/min. Rats in the control group underwent no running. MAIN OUTCOME MEASURES: Rats in the training group was taken for measurement immediate, 3 hours, 24 hours and 48 hours post-exercise respectively. Immunohistochemistry was adopted to determine the proliferating coil nuclear antigen (PCNA) A expression and the vimentin expression in medial head of triceps brachii muscle cells in each group at different phases of repair.RESULTS: The skeletal muscle cell showed sequentially-changed proliferation. The proliferation index of the training group was significantly higher than that of the control group immediately post-exercise. At hour 24 post-exercise, it reached the peak. Hour 48 post-exercise saw the decreased proliferation. The expression of vimentin also exhibits a sequential change after exercise. Moreover, its immunoreaction score changed with time in the same direction with the proliferation index, but there is no correlation between the two.CONCLUSION: Three days of repeated exhausting eccentric exercise can induce the sequential changes of skeletal muscle cell proliferation and vimentin expressions. Vimentin expression has some kinds of correlations with skeletal muscle cell proliferation, but it is not the only factor that matters.
ABSTRACT
With the reformation of university education system,cultivating technological talents and creative talents is proposed,so the laboratory teaching in sports anatomy reformation is imperative.The laboratory teaching in sports anatomy is based on anatomical knowledge,relied on the sport practice.Its goal is to solve the practical problem in P E Work.At present,experimental class hour is limited and the experiment content does not accord with its major,and the experiment examination method is not reasonable.This paper puts forward reforming the experimental class hours,changing experiment items and reforming the examine method,which will drive the innovation of sports anatomy course system