Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats.
Lipopolysaccharide (LPS) is often used to investigate the exacerbatory effects of an immune-related challenge in transgenic models of various neurodegenerative diseases. However, the effects of this inflammatory challenge in an insulin resistant brain state, as seen in diabetes mellitus, a major risk factor for both vascular dementia (VaD) and Alzheimer's disease (AD), is not as well characterized. We investigated the effects of an LPS-induced inflammatory challenge on behavioral and biological parameters following intracerebroventricular (ICV) injection of streptozotocin (STZ) in male Sprague-Dawley rats. Subjects received a one-time bilateral ICV infusion of STZ (25 mg/mL, 8 μL per ventricle) or ACSF. One week following ICV infusions, LPS (1 mg/mL, i.p.) or saline was administered to activate the immune system. Behavioral testing began on the 22nd day following STZ-ICV infusion, utilizing the open field and Morris water maze (MWM) tasks. Proteins related to immune function, learning and memory, synaptic plasticity, and key histopathological markers observed in VaD and AD were evaluated. The addition of an LPS-induced immune challenge partially attenuated spatial learning and memory deficits in the MWM in STZ-ICV injected animals. Additionally, LPS administration to STZ-treated animals partially mitigated alterations observed in several protein levels in STZ-ICV alone, including NR2A, GABA(B1), and β-amyloid oligomers. These results suggest that an acute LPS-inflammatory response has a modest protective effect against some of the spatial learning and memory deficits and protein alterations associated with STZ-ICV induction of an insulin resistant brain state.
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.
Andrew S
AS
Murtishaw
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.
Chelcie F
CF
Heaney
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.
Monica M
MM
Bolton
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.
Jonathan J
JJ
Sabbagh
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.
Michael A
MA
Langhardt
Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA. Electronic address: Jefferson.Kinney@unlv.edu.
Jefferson W
JW
Kinney
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000903:Antibiotics, Antineoplastic; D020662:Guanine Nucleotide Exchange Factors; D015850:Interleukin-6; C102365:Kalrn protein, rat; D008070:Lipopolysaccharides; D018080:Receptors, GABA-B; D047888:Receptors, Tumor Necrosis Factor, Type I; D013311:Streptozocin
Alzheimer's disease; Diabetes; Insulin resistant brain state; Lipopolysaccharide; Neuroinflammation; Streptozotocin; Vascular dementia