The emergence of a new science of the mind: immunology benefits the mind

Schwartz, Michal

doi:10.1038/mp.2010.22

Cited by 9 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of these genes are expressed in the brain, some with potential to affect neurophysiology, neurodevelopment and function and a set of them are known to show altered expression in schizophrenia (www.schizophreniaforum.org). Also of significance is the observation that the FAM19A5 protein encoded by the FAM19A5 gene (22q13.32) belongs to the TAFA protein family which are predominantly expressed in the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells [32]. This finding adds to the existing speculation about the role of the Major Histocompatability Loci (MHC) and infection in SCZ.…”

Section: Resultsmentioning

confidence: 92%

Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

et al. 2011

View full text Add to dashboard Cite

Genetic individuality is the foundation of personalized medicine, yet its determinants are currently poorly understood. One issue is the difference between monozygotic twins that are assumed identical and have been extensively used in genetic studies for decades [1]. Here, we report genome-wide alterations in two nuclear families each with a pair of monozygotic twins discordant for schizophrenia evaluated by the Affymetrix 6.0 human SNP array. The data analysis includes characterization of copy number variations (CNVs) and single nucleotide polymorphism (SNPs). The results have identified genomic differences between twin pairs and a set of new provisional schizophrenia genes. Samples were found to have between 35 and 65 CNVs per individual. The majority of CNVs (∼80%) represented gains. In addition, ∼10% of the CNVs were de novo (not present in parents), of these, 30% arose during parental meiosis and 70% arose during developmental mitosis. We also observed SNPs in the twins that were absent from both parents. These constituted 0.12% of all SNPs seen in the twins. In 65% of cases these SNPs arose during meiosis compared to 35% during mitosis. The developmental mitotic origin of most CNVs that may lead to MZ twin discordance may also cause tissue differences within individuals during a single pregnancy and generate a high frequency of mosaics in the population. The results argue for enduring genome-wide changes during cellular transmission, often ignored in most genetic analyses.

show abstract

Section: Resultsmentioning

confidence: 92%

Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Groundbreaking studies by Kipnis and Schwartz 37, 38, 39 has put CD4 + T cells at the center stage of neuroimmunology. 2 Repopulation of scid mice with T cells from WT donors has been shown to improve significantly the impaired cognitive functions of these mice.…”

Section: Discussionmentioning

confidence: 99%

CD4+ but not CD8+ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice

et al. 2013

View full text Add to dashboard Cite

An imbalanced immune system has long been known to influence a variety of mood disorders including anxiety, obsessive-compulsive disorders and depression. In this study, we sought to model the impact of an immunocompromised state on these emotional behaviors using RAG-1−/− mice, which lack T and B cells. We also investigated the relative contribution of CD4+ or CD8+ T cells to these manifestations using RAG-1−/−/OT-II and RAG-1−/−/OT-I transgenic mice, respectively. Our results show that RAG-1−/− mice present a significant increase in digging and marble-burying activities compared with wild-type mice. Surprisingly, these anxiety-like behaviors were significantly reverted in RAG-1−/−/OT-II but not RAG-1−/−/OT-I transgenic mice. Immunodepletion experiments with anti-CD4 or anti-CD8 in C57/BL6 mice or repopulation studies in RAG-1−/− mice did not reproduce these findings. Microarray analysis of the brain of RAG-1−/− and RAG-1−/−/OT-II mice revealed a significantly different gene fingerprint, with the latter being more similar to wild-type mice than the former. Further analysis revealed nine main signaling pathways as being significantly modulated in RAG-1−/− compared with wild-type mice. Taken together, these results suggest that life-long rather than transient immunodeficient conditions influence the emotional behaviors in mice. Most interestingly, these effects seem to correlate with a specific absence of CD4+ rather than CD8+ T cells. Validation of these findings in man might provide new clues on the mechanism by which early life immune modulation might impact mood response in adults and provide a further link between immune and emotional well-being.

show abstract

“…Evidence suggests these cell types may have established a physiological connection between the immune system and the brain, and have assisted in explaining processes of HC-dependent neurogenesis and cognitive dysfunction (Kipnis et al, 2004b; Butovsky et al, 2006b, 2007; Ziv et al, 2006; Brynskikh et al, 2008; Derecki et al, 2010, 2011), anxiety- and depression-like behavior (Cohen et al, 2006; Lewitus et al, 2008; Cardon et al, 2010) due to an insufficient immune response (Derecki et al, 2010, 2011; Schwartz and Shechter, 2010a,b; Ron-Harel et al, 2011). The role of these cells in neuroprotection and higher neurocognitive functions has been reviewed in detail elsewhere (Martino et al, 2011; Yirmiya and Goshen, 2011); however, a brief summary will be given, below.…”

Section: Neuroimmunological Effects Of Physical Activity In Depressionmentioning

confidence: 99%

“…Cellular immune factors include various T cells [e.g., CD4+CD25+ T regulatory cells (T regs), CNS-specific autoreactive CD4+ T cells] and macrophages (e.g., M2-type blood-derived macrophages) involved in the model of protective immunosurveillance (Schwartz and Shechter, 2010a,b; Martino et al, 2011; Ron-Harel et al, 2011). These neuroprotective immune cells – found to release neurotrophic factors and anti-inflammatory cytokines (AICs; Schwartz and Shechter, 2010a,b; Martino et al, 2011; Ron-Harel et al, 2011) – may be dysfunctional in the disease state (Schwartz and Shechter, 2010b). Moreover, the function of immunomodulatory proteins such as CX3CL1 (aka fractalkine; Rogers et al, 2011; Corona et al, 2012; Giunti et al, 2012), insulin-like growth factor-1 (IGF-1; Park et al, 2011a), and CD 200 (Lyons et al, 2007; Ojo et al, 2012) may be reduced.…”

mentioning

confidence: 99%

Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective

Eyre¹,

Papps²,

Baune³

2013

Front. Psychiatry

View full text Add to dashboard Cite

The increasing burden of major depressive disorder makes the search for an extended understanding of etiology, and for the development of additional treatments highly significant. Biological factors may be useful biomarkers for treatment with physical activity (PA), and neurobiological effects of PA may herald new therapeutic development in the future. This paper provides a thorough and up-to-date review of studies examining the neuroimmunomodulatory effects of PA on the brain in depression and depression-like behaviors. From a neuroimmune perspective, evidence suggests PA does enhance the beneficial and reduce the detrimental effects of the neuroimmune system. PA appears to increase the following factors: interleukin (IL)-10, IL-6 (acutely), macrophage migration inhibitory factor, central nervous system-specific autoreactive CD4+ T cells, M2 microglia, quiescent astrocytes, CX3CL1, and insulin-like growth factor-1. On the other hand, PA appears to reduce detrimental neuroimmune factors such as: Th1/Th2 balance, pro-inflammatory cytokines, C-reactive protein, M1 microglia, and reactive astrocytes. The effect of other mechanisms is unknown, such as: CD4+CD25+ T regulatory cells (T regs), CD200, chemokines, miRNA, M2-type blood-derived macrophages, and tumor necrosis factor (TNF)-α [via receptor 2 (R2)]. The beneficial effects of PA are likely to occur centrally and peripherally (e.g., in visceral fat reduction). The investigation of the neuroimmune effects of PA on depression and depression-like behavior is a rapidly developing and important field.

show abstract

The emergence of a new science of the mind: immunology benefits the mind

Cited by 9 publications

References 14 publications

Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

CD4+ but not CD8+ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice

Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective

Contact Info

Product

Resources

About