Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats

Autor: Ehrlich, D., Pirchl, M., Humpel, C.
Jazyk: angličtina
Předmět:
Male
Neuroscience(all)
IL-1β
interleukin 1-β
NGF
nerve growth factor
WRME
working-reference memory error
Hypercholesterolemia
IgG
immunoglobulin G
PBS
phosphate-buffered saline
nbM
basal nucleus of Meynert
tPA
tissue-plasminogen activator
Time
Aβ
beta-amyloid
Rats
Sprague-Dawley
Alcohol-Induced Disorders
Nervous System
APP
amyloid precursor protein
ChAT
choline-acetyltransferase
mental disorders
Animals
BBB
blood–brain barrier
ANOVA
analysis of variance
MIP-2
macrophage inflammatory protein-2
ACh
acetylcholine
RME
reference memory error
WME
working memory errors
Dementia
Vascular
TNF-α
tumor necrosis factor-alpha
RET
retention
Neurodegeneration
Neuroprotection
and Disease-Oriented Neuroscience
ELISA
enzyme-linked immunosorbent assay
T-PBS
triton/PBS
cognitive decline
Cholinergic Neurons
Rats
Disease Models
Animal
HPLC
high-performance liquid chromatography
AD
Alzheimer's disease
ethanol
Inflammation Mediators
blood–brain barrier leakage
EtOH
ethanol
cholinergic dysfunction
Research Paper
Zdroj: Neuroscience
ISSN: 0306-4522
DOI: 10.1016/j.neuroscience.2011.12.054
Popis: There is strong evidence that vascular risk factors play a role in the development of Alzheimer's disease (AD) or vascular dementia (vaD). Ethanol (EtOH) and cholesterol are such vascular risk factors, and we recently showed that hypercholesterolemia causes pathologies similar to AD [Ullrich et al. (2010) Mol Cell Neurosci 45, 408–417]. The aim of this study was to investigate the effects of long-term (12 months) EtOH treatment (20% v/v in drinking water) alone or long-term 5% cholesterol diet alone or a combination (mix) in adult Sprague–Dawley rats. Long-term EtOH treatment (plasma EtOH levels 58±23 mg/dl) caused significant impairment of spatial memory, reduced the number of choline acetyltransferase- and p75 neurotrophin receptor-positive nucleus basalis of Meynert neurons, decreased cortical acetylcholine, elevated cortical monocyte chemoattractant protein-1 and tissue-type plasminogen activator, enhanced microglia, and markedly induced anti-rat immunoglobulin G-positive blood–brain barrier leakage. The effect of long-term hypercholesterolemia was similar. Combined long-term treatment of rats with 20% EtOH and 5% cholesterol (mix) did not potentiate treatment with EtOH alone, but instead counteracted some of the EtOH-associated effects. In conclusion, our data show that vascular risk factors EtOH and cholesterol play a role in cognitive impairment and possibly vaD.
Highlights ▶Long-term chronic ethanol causes cognitive impairment in rats in vivo. ▶Chronic ethanol causes cholinergic neurodegeneration. ▶Chronic ethanol induces cortical rat IgG-influx and MCP-1 upregulation. ▶Chronic mild hypercholesterolemia causes similar impairments. ▶Hypercholesterolemia partly counteracts some of the ethanol-induced effects.
Databáze: OpenAIRE
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