Neurotrophic Factors in Experimental Cerebral Acanthamoebiasis

Abstract

To date, no studies have addressed the role of neurotrophins (NTs) in Acanthamoeba spp. infections in the brain. Thus, to clarify the role of NTs in the cerebral cortex and hippocampus during experimental acanthamoebiasis in relation to the host immune status, the purpose of this study was to determine whether Acanthamoeba spp. may affect the concentration of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in brain structures. Our results suggest that at the beginning of infection in immunocompetent hosts, BDNF and NT-3 may reflect an endogenous attempt at neuroprotection against Acanthamoeba spp. infection. We also observed a pro-inflammatory effect of NGF during acanthamoebiasis in immunosuppressed hosts. This may provide important information for understanding the development of cerebral acanthamoebiasis related to the immunological status of the host. However, the pathogenesis of brain acanthamoebiasis is still poorly understood and documented and, therefore, requires further research.

Keywords: Acanthamoeba spp.; brain-derived neurotrophic factor; cerebral cortex; hippocampus; immunological status; nerve growth factor; neurotrophin-3; neurotrophin-4.

Figure 1

Brain-derived neurotrophic factor (BDNF) level (pg/mg protein) in the cerebral cortex and hippocampus in control and infected groups at 8, 16, and 24 days after Acanthamoeba spp. infection (dpi). Data present means ± SD for 6 independent experiments. C, immunocompetent uninfected mice; CS, immunosuppressed uninfected mice; A, immunocompetent Acanthamoeba spp. infected mice; AS, immunosuppressed Acanthamoeba spp. infected mice; solid arrows indicate differences between infected and control mice; * p ≤ 0.05 for the significance of difference (Mann–Whitney U test).

Figure 2

Nerve growth factor (NGF) level (pg/mg protein) in the cerebral cortex and hippocampus in control and infected groups at 8, 16, and 24 days after Acanthamoeba spp. infection (dpi). Data present means ± SD for 6 independent experiments. C, immunocompetent uninfected mice; CS, immunosuppressed uninfected mice; A, immunocompetent Acanthamoeba spp. infected mice; AS, immunosuppressed Acanthamoeba spp. infected mice; solid arrows indicate differences between infected and control mice while dashed arrows indicate differences between brain structures; * p ≤ 0.05 for the significance of difference (Mann–Whitney U test).

Figure 3

Neurotrophin-3 level (ng/mg protein) in the cerebral cortex and hippocampus in control and infected groups at 8, 16, and 24 days after Acanthamoeba spp. infection (dpi). Data present means ± SD for 6 independent experiments. C, immunocompetent uninfected mice; CS, immunosuppressed uninfected mice; A, immunocompetent Acanthamoeba spp. infected mice; AS, immunosuppressed Acanthamoeba spp. infected mice; solid arrows indicate differences between infected and control mice while dashed arrows indicate differences between brain structures; * p ≤ 0.05 for the significance of difference (Mann–Whitney U test).

Figure 4

Neurotrophin-4 level (pg/mg protein) in the cerebral cortex and hippocampus in control and infected groups at 8, 16, and 24 days after Acanthamoeba spp. infection (dpi). Data present means ± SD for 6 independent experiments. C, immunocompetent uninfected mice; CS, immunosuppressed uninfected mice; A, immunocompetent Acanthamoeba spp. infected mice; AS, immunosuppressed Acanthamoeba spp. infected mice; dashed arrows indicate differences between brain structures; * p ≤ 0.05 for the significance of difference (Mann–Whitney U test).

Figure 5

Concentrations of neurotrophin 3 (NT3, ng/mg protein), neurotrophin 4 (NT4, pg/mg protein), brain-derived neurotrophic factor (BDNF, pg/mg protein), and nerve growth factor (NGF, pg/mg protein) in the cerebral cortex of infected immunocompetent (A) and immunosuppressed mice (AS) (pictures (A) and (B), respectively) and in the hippocampus of infected immunocomptent (A) and immunosuppressed mice (AS) (pictures (C) and (D), respectively).