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Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats.
Neuropharmacology. 2016 Feb; 101:110-22.N

Abstract

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.

Authors+Show Affiliations

Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA.Behavioral Neuroscience Laboratory, Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV, USA. Electronic address: Jefferson.Kinney@unlv.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26327677

Citation

Murtishaw, Andrew S., et al. "Effect of Acute Lipopolysaccharide-induced Inflammation in Intracerebroventricular-streptozotocin Injected Rats." Neuropharmacology, vol. 101, 2016, pp. 110-22.
Murtishaw AS, Heaney CF, Bolton MM, et al. Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats. Neuropharmacology. 2016;101:110-22.
Murtishaw, A. S., Heaney, C. F., Bolton, M. M., Sabbagh, J. J., Langhardt, M. A., & Kinney, J. W. (2016). Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats. Neuropharmacology, 101, 110-22. https://doi.org/10.1016/j.neuropharm.2015.08.044
Murtishaw AS, et al. Effect of Acute Lipopolysaccharide-induced Inflammation in Intracerebroventricular-streptozotocin Injected Rats. Neuropharmacology. 2016;101:110-22. PubMed PMID: 26327677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats. AU - Murtishaw,Andrew S, AU - Heaney,Chelcie F, AU - Bolton,Monica M, AU - Sabbagh,Jonathan J, AU - Langhardt,Michael A, AU - Kinney,Jefferson W, Y1 - 2015/08/29/ PY - 2015/03/24/received PY - 2015/08/03/revised PY - 2015/08/26/accepted PY - 2015/9/2/entrez PY - 2015/9/4/pubmed PY - 2016/9/23/medline KW - Alzheimer's disease KW - Diabetes KW - Insulin resistant brain state KW - Lipopolysaccharide KW - Neuroinflammation KW - Streptozotocin KW - Vascular dementia SP - 110 EP - 22 JF - Neuropharmacology JO - Neuropharmacology VL - 101 N2 - 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/26327677/Effect_of_acute_lipopolysaccharide_induced_inflammation_in_intracerebroventricular_streptozotocin_injected_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(15)30089-7 DB - PRIME DP - Unbound Medicine ER -