Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1265136187.pdf (4.6 MB)

ETD Abstract Container

Abstract Header

Neuroinflammation induces time-dependant behavioral, cellular and molecular changes that resemble characteristics of Alzheimer’s and Parkinson’s diseases and can be modulated by caffeine administration

Brothers, Holly M.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1265136187

Abstract Details

2010, Master of Arts, Ohio State University, Psychology.
Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, that may contribute to loss of function and cell death. Cell loss in the hippocampus and cortex is characteristic of Alzheimer’s disease (AD), Parkinson’s disease (PD) is marked by the loss of cells in the substantia nigra (SN), and both the locus coeruleus (LC) and the raphe nucleus are known to be affected in these diseases. Caffeine, an adenosine antagonist, is protective against the risk of AD and PD. The experiments described in this thesis were designed to address the following two hypotheses: If neuroinflammation contributes to the onset/progression of behavioral, cellular and molecular characteristics of AD and PD in a time-dependant manner in the temporal lobe and brainstem, then neuroinflammation created in a young rat by i.c.v. infusion of LPS should reproduce a subset of time-dependant characteristics of AD and PD in these brain regions. If the actions of adenosine at its receptors contribute to the behavioral, cellular and molecular characteristics of AD and PD reproduced by LPS-induced neuroinflammation and natural aging in rats, then modulation of the consequences of neuroinflammation by the adenosine receptor antagonist caffeine should attenuate the disease-like characteristics produced by neuroinflammation and aging. In order to test these hypotheses, young rats (3 months) were implanted with a cannula into the IVth ventricle that was connected to an osmotic minipump filled with either lipopolysaccharide (LPS) or the vehicle (aCSF) for 2, 4 or 8 weeks and modulation by caffeine upon experimentally produced neuroinflammation in LPS-infused young rats and naturally occurring inflammation in aged rats was evaluated. We predicted that LPS-infusion would produce microglia activation (defined as presentation of MHC II) in the hippocampus and brainstem, regions that degenerate in AD and PD, that would increase in intensity over time, evidence of reduced function and potentially death of dopaminergic neurons within the SN that would also increase with time, and corresponding behavioral deficits. Furthermore, we predicted that caffeine, a drug with known epidemiological potential to reduce the incidence of both AD and PD, would attenuate the development of neuroinflammation and the behavioral, cellular and molecular consequences of inflammation in a dose-dependent manner. The infusion of LPS induced pronounced microglia activation and characteristic changes in morphology that increased with the duration of LPS infusion. The regional distribution of microglia presenting MHC II is heterogeneous and was concentrated in the DG of the hippocampus, SN, LC and raphe as compared to other regions, indicating that those regions most vulnerable to degeneration in a disease state are those with the greatest propensity to develop reactive microglia to an inflammagen. Rats that received LPS performed poorly in the Morris water maze, a task known to be sensitive to the integrity of the hippocampus. LPS-infused rats also displayed reduced production of tyrosine hydroxylase and therefore reduced dopamine synthesis in the SN and displayed dysmorphic neuronal structure in LC and the raphe nucleus.
Gary Wenk, PhD (Advisor)
Gary Berntson, PhD (Committee Member)
John Bruno, PhD (Committee Member)
239 p.
Psychology
inflammation Alzheimer's Parkinson's microglia LPS

Recommended Citations

Citations

  • Brothers, H. M. (2010). Neuroinflammation induces time-dependant behavioral, cellular and molecular changes that resemble characteristics of Alzheimer’s and Parkinson’s diseases and can be modulated by caffeine administration [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1265136187

    APA Style (7th edition)

  • Brothers, Holly. Neuroinflammation induces time-dependant behavioral, cellular and molecular changes that resemble characteristics of Alzheimer’s and Parkinson’s diseases and can be modulated by caffeine administration. 2010. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1265136187.

    MLA Style (8th edition)

  • Brothers, Holly. "Neuroinflammation induces time-dependant behavioral, cellular and molecular changes that resemble characteristics of Alzheimer’s and Parkinson’s diseases and can be modulated by caffeine administration." Master's thesis, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1265136187

    Chicago Manual of Style (17th edition)

osu1265136187
1,052
© 2010, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.