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Immunoglobulin-Mediated Neuro-Cognitive Impairment: New Data and a Comprehensive Review

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Abstract

Excessive influx of immunoglobulin (IgG) into the brain has been reported to induce central nervous system (CNS) dysfunction. Depressed patients may exhibit immune activation manifested by elevated inflammatory markers and pro-inflammatory cytokines. The brain and especially the limbic system contain high concentrations of high affinity Fc receptors. We reviewed the literature on this phenomena and present data on the behavioral effects of pooled normal IgG on the brain. Many disease states are associated with depression and we examined whether this may be linked to high IgG influx. Female Balb/C mice were injected intra-cerbroventricularly with human immunoglobulin whole molecule, or human IgG F(ab′)2 or Fc fragments. Control mice were injected with saline. The four groups were subjected to behavioral (staircase, forced swimming test, and elevated plus maze) and cognitive tests (passive avoidance test). IgG-injected mice exhibited depression-like behavior as reflected by significantly higher immobility time in the forced swimming test (p < 0.05) and hyperactive behavior as reflected by higher number of stairs climbed in the staircase test compared to controls (p < 0.01). Fc-fragments-injected mice showed hyperactive behavior as reflected by both higher number of stairs climbed and rearing events in the staircase test compared to controls. The results indicate that high levels of normal IgG in the cerebrospinal fluid can cause hyperactivity and depression-like behavior. The mechanism involved in these CNS manifestations include possibly Fc receptor binding.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 66978, Israel

    Assaf Menachem, Joab Chapman & Yael Deri

  2. Department of Neurology and Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Assaf Menachem, Joab Chapman, Yael Deri & Aviva Katzav

  3. The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 52621, Israel

    Joab Chapman & Aviva Katzav

  4. Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 66978, Israel

    Chaim G. Pick

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  1. Assaf Menachem
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  2. Joab Chapman
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  3. Yael Deri
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  4. Chaim G. Pick
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  5. Aviva Katzav
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Correspondence to Aviva Katzav.

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Menachem, A., Chapman, J., Deri, Y. et al. Immunoglobulin-Mediated Neuro-Cognitive Impairment: New Data and a Comprehensive Review. Clinic Rev Allerg Immunol 45, 248–255 (2013). https://doi.org/10.1007/s12016-013-8357-z

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