Thesis (Ph.D.(Physiology))--University of the Witwatersrand, Faculty of Health Sciences, 2012. / The acute phase response is implemented by infected hosts in response to exposure to
pathogens, including bacteria and viruses. Acute phase responses comprise physiological
and behavioural changes, such as fever and a range of “sickness behaviours”, including
lethargy and anorexia as well as impairment in learning and memory. Similar to other
sickness behaviours, the effect of infection on learning and memory processes has been
attributed to the release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and
interleukin-6 (IL-6). However, the exact role of IL-1β and IL-6 in mediating infection-induced
cognitive impairment is not clear. Unlike fever, anorexia and lethargy, which may benefit an
infected host, the physiological benefit of cognitive impairment during illness is doubtful.
To initiate an acute phase response experimentally, moieties of typical bacteria (Gramnegative
and Gram-positive) and viruses frequently are employed. Moieties from the atypical
Mycoplasmas seldom have been used. Consequently, there is a dearth of information on the
physiological mechanisms that underlie acute phase responses following Mycoplasma
infection, despite the prevalence of the disease in the general population. Mycoplasma
pneumoniae frequently causes community-acquired pneumonia, which may have serious
extra-pulmonary complications, including cognitive deficits. Therefore, I investigated fever
and sickness behaviours as well as cytokine responses in simulated, atypical Mycoplasma
infection.
I implemented an animal model of simulated Mycoplasma infection and characterised fever
and sickness behaviours, including lethargy and anorexia as well as impairment in learning
and memory during acute and recurrent acute simulated infection. I also characterized the
response in the periphery and in the brain of individual pro-inflammatory cytokines, IL-1β
and IL-6, to administration of fibroblast-stimulating lipopeptide-1 (FSL-1), which simulates Mycoplasma infection. Using rats, I recorded fever and lethargy with biotelemetry and
assessed effects of simulated Mycoplasma infection on learning and memory using a Morris
Water Maze. In addition, I examined the histology of tissue from the hippocampus, a key
brain area involved in spatial learning and memory, to assess residual effects of simulated
Mycoplasma infection on learning and memory.
I showed that bolus administration of a pyrogenic moiety from Mycoplasma, fibroblaststimulating
lipopeptide-1 (FSL-1), dose-dependently induced fever, lethargy, anorexia and
body mass stunting in rats. However, FSL-1 administration did not induce concomitant
impairment in spatial learning and memory. Importantly, at the time of testing in the Maze, I
found the concentrations of IL-1β to be up-regulated in both the hypothalamus and the
hippocampus, while the concentrations of IL-6 were unaffected. I also showed that recurrent
acute injections of FSL-1, at 10 d intervals, induced recurrent fevers, lethargy and anorexia
without the development of pyrogenic tolerance to any of the sickness responses measured.
However, there was no residual body mass stunting in rats and also no growth retardation,
despite the recurrent simulated infection. Equally importantly, there were neither lasting
detrimental effects on spatial learning and memory nor any residual histological damage to
the hippocampus of rats.
My findings in simulated Mycoplasma infection are important, firstly because Mycoplasma
infection is prevalent in both developing and developed countries and frequently causes
outbreaks, and secondly because Mycoplasma infection affects children and adolescents of
school-going age. My findings also are encouraging: although lasting detrimental effects,
including impairment in learning and memory as well as body mass stunting may occur in
other infections, these appear not to be inevitable outcomes in Mycoplasma infection.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/12489 |
| Date | 05 March 2013 |
| Creators | Swanepoel, Tanya |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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