Abstract
BackgroundPrevious studies in aging animals have shown that amyloid-beta protein (Aβ) 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 Aβ 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 Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.MethodsHydrocephalus 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, Aβ, 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.ResultsWhen 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, 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 Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.ConclusionNeonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.
Highlights
Previous studies in aging animals have shown that amyloid-beta protein (Aβ) 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
The present study has examined LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) in neonatal animals after intraventricular hydrocephalus was induced by kaolin injections into the cisterna magna at 1 day of age and ventriculomegaly had progressed until 21 days of age
The cerebral aqueduct was normal in the saline controls (Fig 1C) but in the hydrocephalic animals was expanded caudally creating a possible communication to the subarachnoid space (SAS) that overlies the dorsal surface of the midbrain (Fig 1D)
Summary
Previous studies in aging animals have shown that amyloid-beta protein (Aβ) 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. Hydrocephalus is a condition characterized by an excessive build up of cerebrospinal fluid (CSF) in the cerebral ventricles. This condition is most frequently found in children and occurs in aged adults. All forms of hydrocephalus exhibit impairment in CSF flow and absorption. Accumulation of Aβ is associated with Alzheimer-type dementia and is commonly found in the CSF of adults with normal pressure hydrocephalus (NPH) and in brain tissue from adult rat models of this disorder. Accumulation of Aβ is associated with Alzheimer-type dementia and is commonly found in the CSF of adults with normal pressure hydrocephalus (NPH) and in brain tissue from adult rat models of this disorder. [7,10,11,12,13,14,15,16]
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