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 (Aa) 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 Aa 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 Aa 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, Aa, 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 Aa, 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 Aa, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP. Conclusion: Neonatal rats with and without hydrocephalus had low expression of Aa and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aa and its transporters between the control and hydrocephalic neonatal animals.