Hippocampal overexpression of Down syndrome cell adhesion molecule in amyloid precursor protein transgenic mice

Abstract

Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We previously demonstrated DSCAM overexpression in the cortex of amyloid precursor protein (APP) transgenic mice, suggesting possible regulatory interactions between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent learning and memory. In this preliminary study, we examined age-related changes in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and 12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and age-matched wild type littermates (WTs) using the Morris water maze (MWM). The cellular distribution of hippocampal DSCAM and total expression at both mRNA and protein levels were measured by immunohistochemistry, qRT-PCR, and western blotting, respectively. APP mice exhibited spatial memory deficits in the MWM. Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and protein expression levels were substantially higher in APP mice than WTs at 1 and 3 months of age. Expression decreased with age in both groups but remained higher in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months of life in APP mice, but especially during maturation to adulthood. In conclusion, these results suggest an association between DSCAM and APP mice, which is characterized by neuropathology and behavioral deficits. These results provide some clues for future studies on the role of DSCAM overexpression in the precocious cognitive decline observed in APP transgenic mice.

A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal Function

“…This difference could be due to the well‐documented neuroprotective effects of amifostine, particularly with regard to neurite formation and length. [ 58–60 ] Our data suggests that we are able to detect the neuroprotective effects of amifostine against minor adverse culture conditions (i.e., vibration during transportation and temperature change while out of the incubator) experienced by the untreated samples during mock irradiation, since these samples underwent all of the same treatment steps that the GR treated samples underwent, short of GR exposure.”. Oxidative stress is widely known to induce neurite degeneration, both in vivo and in vitro .…”

Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome

“…Our circRNA-based analysis for GRIK1 showed that multiple signaling pathways were implicated in neuropathogenesis. The axon guidance pathway was involved in the formation of neural circuitry through nervous system development, and abnormal axon guidance may contribute to the reduction of long-distance connectivity formation and other DS brain phenotypes (Jia et al, 2017). Pharmacological stimulation of BDNF signaling could rescue synaptic plasticity and memory deficits in Ts65Dn mice (Parrini et al, 2017).…”

Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier

“…Only 12 overlapping genes were altered in the same direction in the NVU of both ageing human and mouse cohorts, including genes which play an important role in regulating vascular tone ( ARHGAP42 ) [41]; cell adhesion, neurite outgrowth and axon guidance ( DSCAM ) [42]; repression of tight junction protein expression ( SNAI2 ) [43,44]; cellular stress-response ( ERLEC1 ) [45]; learning, memory and synaptic development ( GRIN2C ) [46], all processes prone to dysregulation with advancing age.…”