Proinflammatory cytokines differentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration - PubMed (original) (raw)

Proinflammatory cytokines differentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration

Julie Anne Seguin et al. Neuropsychiatr Dis Treat. 2009.

Abstract

Disturbances of hippocampal plasticity, including impaired dendritic branching and reductions of neurogenesis, are provoked by stressful insults and may occur in depression. Although corticoids likely contribute to stressor-induced reductions of neurogenesis, other signaling messengers, including pro-inflammatory cytokines might also be involved. Accordingly, the present investigation assessed whether three proinflammatory cytokines, namely interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) (associated with depression) influenced cellular proliferation within the hippocampus. In this regard, systemic administration of TNF-alpha reduced 5-bromo-2-deoxyuridine (BrdU) labeling within the hippocampus, whereas IL-1beta and IL-6 had no such effect. However, repeated but not a single intra-hippocampal infusion of IL-6 and IL-1beta actually increased cellular proliferation and IL-6 infusion also enhanced microglial staining within the hippocampus. Yet, no changes in doublecortin expression were apparent, suggesting that the cytokine did not influence the birth of cells destined to become neurons. Essentially, the route of administration and chronicity of cytokine administration had a marked influence upon the nature of hippocampal alterations provoked, suggesting that cytokines may differentially regulate hippocampal plasticity in neuropsychiatric conditions.

Keywords: cytokine; depression; hippocampus; neuroplasticity; stressor.

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Figures

Figure 1

Figure 1

BrdU immunopositive cells are depicted in the photomicrographs of the rostral portion of hippocampal dentate gyrus of animals subjected to i.p. injection of A) saline, B) IL-1β (0.1 μg), C) TNF-α (1.0 μg) or (d) IL-6 (1.0 μg). There was a clear reduction of BrdU-labelled cells in mice that received TNF-α (panel C), relative to saline injected controls (panel A). The bottom bar graph displays the mean (± SEM) number of BrdU-positive cells per section and confirms the suppression of BrdU labeling following systemic administration of TNF-α. Notes: *p < 0.05 vs. saline-treated animals, 10× magnification.

Figure 2

Figure 2

The photomicrographs (4× magnification) show doublecortin (DCX) positive immature neurons within the dentate gyrus of the rostral portion of dorsal hippocampus. There was no significant difference in DCX expression between mice that received i.p. saline A) or those treated with i.p. TNF-α B) The inset (upper right corner of panel A) reveals a higher magnification (20×) image of the DCX positive soma and projections from a saline-treated animal.

Figure 3

Figure 3

The photomicrographs depict BrdU-positive cells within the dentate gyrus following a single or repeated intra-hippocampal cytokine or saline infusion. Elevated BrdU staining within the dentate gyrus was observed in animals subjected to repeated intra-hippocampal infusion of either IL-1β (panel B) or IL-6 (panel C), relative to animals that received vehicle (panel A). The BrdU increase was particularly robust for the repeated IL-6 treatment. Quantification of mean (± SEM) number of BrdU-positive cells per section confirmed that repeated (grey bars) but not a single (white bars) intra-hippocampal infusion of IL-1β and IL-6 significantly increased BrdU staining, relative to animals that received infusion of saline. Notes: *p < 0.05 vs saline-treated animals, 10× magnification.

Figure 4

Figure 4

Photomicrographs of labeling for the microglial marker, CD11b, in animals subjected to a single or repeated intra-hippocampal infusions of saline or IL-6. The CD11b immunoreactivity was evident in the granule cell layer (GCL) of the dentate gyrus, as well as within the CA1 hippocampal region. Single (A) and repeated (B) infusion of saline provoked minimal CD11b staining in the GCL and CA1. Although the single IL-6 infusion (C) induced modest CD11b immunoreactivity, repeated infusion of the cytokine (D) produced the most marked increase of expression of the microglial marker within the GCL and CA1 areas of the hippocampus. 4× magnification.

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References

    1. Dunn AJ. The role of interleukin-1 and tumor necrosis factor alpha in the neurochemical and neuroendocrine responses to endotoxin. Brain Res Bull. 1992;29:807–812. - PubMed
    1. Hayley S, Anisman H. Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: Neurochemical and molecular substrates. Curr Pharm Des. 2005;11:947–962. - PubMed
    1. Hopkins SJ, Rothwell NJ. Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci. 1995;18:83–88. - PubMed
    1. Weigent DA, Carr DJ, Blalock JE. Bidirectional communication between the neuroendocrine and immune systems. common hormones and hormone receptors. Ann N Y Acad Sci. 1990;579:17–27. - PubMed
    1. Hayley S, Lacosta S, Merali Z, van Rooijen N, Anisman H. Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: Sensitization and cross-sensitization effects. Eur J Neurosci. 2001;13:1155–1165. - PubMed

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