DSCAM's Expression Changes In The Brain Of APP Transgenic Mouse

Background & ObjectiveDown's syndrome phenotype is determined by chromosome 21 specific gene control region which is the critical region of Down's syndrome. In DS critical region, the increase of genes causing overexpression of its product is considered to be the reason causing clinical manifestations of DS. Neuropathological studies in DS have found including the congenital or acquired deformities and correlative changes in the early appearance of dementia. The former includes the decreases of granulosa cells in cerebral cortex, which is may associated with the type of the aspinous astrocytes, and the decrease of dendritic spines and anomaly spinous structure of neuron in infancy and adulthood, the latter takes the senile plaque in cortex of prefrontal and hippocampus and neurofibrillary tangles (NFT)as representatives. Excess of the above genes may explain some of the changes, while the other unrecognized genes in Down syndrome critical region (DSOR) may be involved in the disease process of DS. A new gene called the Down syndrome adhesion molecule (DSCAM) was identified in DSOR, it located on chromosome 21q22. The molecule has the homologous sequence with Immunoglobulin superfamily (IgSF) members, which suggests its functions as a adhesion molecules. Study found that DSCAM was expressed in most of the developing nervous system, which suggested that it may participate the neuronal migration, proliferation, differentiation, growth and development, maintenance, connection, axon guidance and to find the target function, the mutual recognition between synaptics and self-avoidance, it also suggested overexpression of DSCAM may related to presenile dementia, mental retardation and the peripheral Nerves defects in DS patients. Thus far, there is no proven link between genes in the DSCAM and the mental and behavioral abnormalities associated with dementia in Alzheimer's disease (AD). In this study, through immunohistochemistry, immunofluorescence, Western Blot and RT-PCR, we explored the role of DSCAM in AD by examining its expression in the brain of an AD animal model—C57BL/6J-APP mice, and though comparing with negative control mice to explore the role of DSCAM in dementia and abnormal behavior of APP transgenic mice.Materials and MethodsWith immunohistochemistry, immumofluorescence, Western Blot and RT-PCR, the expression of DSCAM in the brains of APP positive transgenic mice (aged newborn, 1m,3m,6m,12m) was detected, especially the expression pattern of location and strength in cerebellum and cerebral cortex. The control groups are brains of negative mice (aged newborn, 1m,3m,6m,12m).ResultsWe have found that DSCAM is widely expressed in the cerebellar purkinje cell, the cerebral cortex, the hippocampal pyramidal cell layer of Ammon's horn, the granular layer of the dentate gyrus, and the thalamus and brain stem's neurons in APP positive transgenic mice. In the cerebellum, there isn't a noticeable distinction for the expression of DSCAM in newborn and 1 month old mice(P>0.05); the expression of DSCAM in the 3 month old mice is greater than the 1 month mice(P<0.05); there isn't a noticeable difference for the expression of DSCAM in 3 month and 6 month mice(P>0.05); at 12 months of age, the expression levels appear to decrease(P< 0.05). At 3 months and 6 months of age, the expression levels are remarkably higher than the control groups in cerebellum(P<0.05). We also demonstrated that the expression of DSCAM in the cerebral cortex of APP transgenic mice increased with age to a peak at 3 months old (P<0.05). There was no difference in DSCAM expression between 3-month-old and 6-month-old mice (P>0.05). The cerebral cortex expression levels of DSCAM in the APP transgenic mice were all higher than their respective levels in the age-matched wild types (P<0.05)ConclusionsDSCAM presents to overexpression in APP transgenic mice cerebellum and cerebral cortex. As a result, we suppose that DSCAM's overexpression may contribute to the defects in the ability of motion and motion coordination, learning and memory as a cell adhesion molecule.