Adaptive immunity affects learning behavior in mice.
ABSTRACT Regulation of neuronal plasticity by the immune system is an evolving field of modern neuroscience. Here we employ immune deficient mice to examine the role of the immune system in learning behavior of mice in a variety of cognitive tasks. While no motivation or motor function deficits are evident in severe combined immune deficient (scid) mice, there was significant impairment in acquisition of cognitive tasks as compared to wild-type (WT) control mice. Moreover, acute depletion of adaptive immunity in adult WT mice significantly impaired learning behavior. Passive transfer of autologous T cells into WT mice following ablation of adaptive immunity restored previously impaired cognitive function. These results suggest that throughout lifetime, immune system supports cognitive function and may therefore have far-reaching therapeutic implications for cognitive disorders.
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ABSTRACT: Mice with severe combined immunodeficiency (SCID) lack functional T and B lymphocytes, and have impaired cognitive abilities. We assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse. In a social recognition task, SCID mice habituated to a novel ovariectomized mouse, but failed to show dishabituation when presented with an unfamiliar individual. We hypothesized that partial immune restoration could normalize behaviors. SCID pups (postnatal Day 7) received either saline or splenocytes from normal donors. Splenocyte-replaced SCID mice spent less time interacting with a novel mouse than saline-injected SCID or B6 control mice. Again, control SCID mice failed to dishabituate to a novel mouse, but splenocyte-replaced SCID mice showed dishabituation. In both of these studies, B6 and SCID pairs were used to produce offspring that remained with their dams until weaning. There are no studies of maternal behavior in SCID dams; therefore to investigate the potential role for this factor, we quantified maternal behavior in SCID and B6 dams; several significant differences were found. To control for differences in maternal care, we mated heterozygous SCIDs to produce offspring. These homozygous SCID and wild-type offspring reared by dams of the same genotypes displayed similar responses to a novel mouse; however, in the social recognition task, SCID males did not display dishabituation to a novel mouse. Taken together, our data indicate that Gene × Environment interactions influence social interactions in immune deficient mice. (PsycINFO Database Record (c) 2015 APA, all rights reserved).Behavioral Neuroscience 06/2015; 129(3):331-338. DOI:10.1037/bne0000053 · 3.25 Impact Factor
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ABSTRACT: Coevolution of microbes and their hosts has resulted in the formation of symbiotic relationships that enable animals to adapt to their environments and protect themselves against pathogens. Recent studies show that contact with tolerogenic microbes is important for the proper functioning of immunoregulatory circuits affecting behavior, emotionality and health. Few studies have examined the potential influence of ambient bacteria, such as Mycobacterium vaccae on the gut-brain-microbiota axis. In this preliminary research, we show that mice fed live M. vaccae prior to and during a maze learning task demonstrated a reduction in anxiety-related behaviors and maze completion time, when tested at three maze difficulty levels over 12 trials for four weeks. Treated mice given M. vaccae in their reward completed the maze twice as fast as controls, and with reduced anxiety-related behaviors. In a consecutive set of 12 maze trials without M. vaccae exposure, treated mice continued to run the maze faster for the first three trials, and with fewer errors overall, suggesting a treatment persistence of about one week. Following a three-week hiatus, a final maze run revealed no differences between the experimentals and controls. Additionally, M. vaccae-treated mice showed more exploratory head-dip behavior in a zero maze, and M. vaccae treatment did not appear to affect overall activity levels as measured by activity wheel usage. Collectively, our results suggest a beneficial effect of naturally delivered, live M. vaccae on anxiety-related behaviors and maze performance, supporting a positive role for ambient microbes in the immunomodulation of animal behavior.Behavioural processes 02/2013; DOI:10.1016/j.beproc.2013.02.007 · 1.46 Impact Factor
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ABSTRACT: 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.Frontiers in Psychiatry 02/2013; 4:3. DOI:10.3389/fpsyt.2013.00003