Abstract
The present study was designed to assess if treatment with acetylcholinesterase inhibitor
galantamine and the cholinergic precursor choline alphoscerate (alpha-glyceryl-phosphoryl-choline)
alone or in association has any protective effect on brain microanatomy in spontaneously
hypertensive rats (SHR) used as an animal model of vascular dementia (VaD). Thirty-two-week-old
SHR and age-matched normotensive Wistar Kyoto (WKY) rats were left untreated or treated
for 4 weeks with an oral dose of 3 mg/kg/day of galantamine, of 100 mg/kg/day of choline
alphoscerate or their association. The number of neurons and of glial fibrillary acidic
protein (GFAP) immunoreactive astrocytes, phosphorylated neurofilament, and microtubule
associated protein-2 (MAP-2) and aquaporin-4 (AQP-4) was assessed by quantitative
microanatomical and immunohistochemical techniques. In SHR, the number of neurons
of frontal cortex, of the CA1 subfield of hippocampus and of dentate gyrus was decreased
compared to WKY rats. Astrogliosis, breakdown of phosphorylated neurofilament, unchanged
MAP-2 and altered AQP-4 expression were found as well. Both galantamine and choline
alphoscerate countered nerve cell loss. Choline alphoscerate but not galantamine decreased
astrogliosis and restored expression of AQ-4. Galantamine countered to a greater extent
than choline alphoscerate phosphorylated neurofilament breakdown. The two drugs in
association displayed a more remarkable effect. This study confirms a neuroprotective
effect of galantamine in SHR and indicates a neuroprotective role of choline alphoscerate
in the same model. A wider neuroprotective effect of the cholinergic inhibitor/precursor
association was observed. These findings suggest to assess the activity of this cholinergic
association in clinical trials.
Keywords
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Article info
Publication history
Published online: March 23, 2009
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© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
