Intra-Hippocampal Transplantation of Neural Precursor Cells with Transgenic Over-Expression of IL-1 Receptor Antagonist Rescues Memory and Neurogenesis Impairments in an Alzheimer’s Disease Model

The bipotential Ganglion Mother Cells, or GMCs, in the DrosophilaCNS asymmetrically divide to generate two distinct post-mitotic neurons. Here,we show that the midline repellent Slit (Sli), via its receptor Roundabout(Robo), promotes the terminal asymmetric division of GMCs. In GMC-1 of the RP2/sib lineage, Slit promotes asymmetric division by down regulating two POU proteins, Nubbin and Mitimere. The down regulation of these proteins allows the asymmetric localization of Inscuteable, leading to the asymmetric division of GMC-1. Consistent with this, over-expression of these POU genes in a late GMC-1 causes mis-localization of Insc and symmetric division of GMC-1 to generate two RP2s. Similarly, increasing the dosage of the two POU genes insli mutant background enhances the penetrance of the RP2 lineage defects whereas reducing the dosage of the two genes reduces the penetrance of the phenotype. These results tie a cell-non-autonomous signaling pathway to the asymmetric division of precursor cells during neurogenesis.

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APP/PS1 Transgenic Mice Treated with Aluminum: An Update of Alzheimer's Disease Model

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201202500107 ◽

2012 ◽

Vol 25 (1) ◽

pp. 49-58 ◽

Cited By ~ 18

Author(s):

Q.L. Zhang ◽

L. Jia ◽

X. Jiao ◽

W.L. Guo ◽

J.W. Ji ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Transgenic Mice ◽

Disease Model ◽

Amyloid Β ◽

Neural Cells ◽

Over Expression ◽

Morris Water Maze Task ◽

Close Relationship

There is still no animal model available that can mimic all the cognitive, behavioral, biochemical, and histopathological abnormalities observed in patients with Alzheimer's disease (AD). We undertook to consider the interaction between genetic factors, including amyloid precursor protein (APP) and presenilin-1 (PS1), and environmental factors, such as Aluminum (Al) in determining susceptibility outcomes when studying the pathogenesis of AD. In this article, we provide an AD model in APP/PS1 transgenic mice triggered by Al. The animal model was established via intracerebral ventricular microinjection of aluminum chloride once a day for 5 days in APP/PS1 transgenic mice. Twenty wild type (WT) mice and 20 APP/PS1 transgenic (TG) mice were separately divided into 2 groups (control and Al group), and a stainless steel injector with stopper was used for microinjection into the left-lateral cerebral ventricle of each mouse. The Morris water maze task was used to evaluate behavioral function of learning and memory ability on the 20th day after the last injection. This AD model's brain was analyzed by: (1) amyloid β immunohistochemical staining; (2) Tunnel staining; (3) apoptotic rates; (4) caspase-3 gene expression. Here, decrease of cognitive ability and neural cells loss were shown in APP/PS1 transgenic mice exposed to Al, which were more extensive than those in APP/PS1 TG alone and WT mice exposed to Al alone. These findings indicate that there is a close relationship between over-expression of APP and PS1 genes and Al overload. It is also suggested that APP/PS1 TG mice exposed to Al have potential value for improving AD models.

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