Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus.
BACKGROUND
Previous studies in aging animals have shown that amyloid-beta protein (Abeta) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Abeta have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Abeta and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.


METHODS
Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Abeta, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP.


RESULTS
When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6-12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Abeta, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Abeta, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.


CONCLUSIONS
Neonatal rats with and without hydrocephalus had low expression of Abeta and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Abeta and its transporters between the control and hydrocephalic neonatal animals.
Deren
Kelley E
KE
Department of Neurosurgery, Division of Pediatric Neurosurgery, Primary Children's Medical Center and the University of Utah, Salt Lake City, Utah 84132, USA. pat.mcallister@hsc.utah.edu.
Forsyth
Jennifer
J
Abdullah
Osama
O
Hsu
Edward W
EW
Klinge
Petra M
PM
Silverberg
Gerald D
GD
Johanson
Conrad E
CE
McAllister
James P
JP