Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life

Yang, Jiliang; Qi, Fangfang; Gu, Huaiyu; Zou, Juntao; Yang, Yang; Yuan, Qing; Ye, Zhibin

doi:10.1016/j.brainresbull.2015.10.012

Cited by 43 publications

(54 citation statements)

References 49 publications

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“…Microglia can be polarized into M1-like and M2-like activation states (Cherry et al, 2014; Edwards et al, 2006). M1 is proinflammatory and may promote psychiatric disorders (Nakagawa and Chiba, 2014) whereas M2 is anti-inflammatory and was associated with elevations in cognition, mood, and neurogenesis in animal inflammation models (Brachman et al, 2015; Yang et al, 2016). Microglia can also facilitate neuronal changes like synaptic plasticity via production of brain-derived neurotrophic factor (BDNF) (Parkhurst et al, 2013).…”

Section: Mechanisms Of Immune-to-brain Influencementioning

confidence: 99%

“…Microglia can also facilitate neuronal changes like synaptic plasticity via production of brain-derived neurotrophic factor (BDNF) (Parkhurst et al, 2013). In many studies, BDNF levels correlate with behavioral outcomes, both positive and negative, suggesting that production of this neurotrophin may be a CNS mediator of the peripheral actions of lymphocytes (Chen et al, 2015; Derecki et al, 2010; Wolf et al, 2009; Yang et al, 2016; Ziv et al, 2006). However, BDNF production levels in cultured microglia were not altered in response to cultured media derived from Th1- or Th2-cell lines (Seguin et al, 2003).…”

Section: Mechanisms Of Immune-to-brain Influencementioning

confidence: 99%

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Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Herkenham

Kigar

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Clinical and basic studies of functional interactions between adaptive immunity, affective states, and brain function are reviewed, and the neural, humoral, and cellular routes of bidirectional communication between the brain and the adaptive immune system are evaluated. In clinical studies of depressed populations, lymphocytes—the principal cells of the adaptive immune system—exhibit altered T cell subtype ratios and CD4+ helper T cell polarization profiles. In basic studies using psychological stress to model depression, T cell profiles are altered as well, consistent with stress effects conveyed by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Lymphocytes in turn have effects on behavior and CNS structure and function. CD4+ T cells in particular appear to modify affective behavior and rates of hippocampal dentate gyrus neurogenesis. These observations force the question of how such actions are carried out. CNS effects may occur via cellular and molecular mechanisms whereby effector memory T cells and the cytokine profiles they produce in the blood interact with the blood-brain barrier in ways that remain to be clarified. Understanding the mechanisms by which T cells polarize and interact with the brain to alter mood states is key to advances in the field, and may permit development of therapies that target cells in the periphery, thus bypassing problems associated with bioavailability of drugs within the brain.

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Section: Mechanisms Of Immune-to-brain Influencementioning

confidence: 99%

Section: Mechanisms Of Immune-to-brain Influencementioning

confidence: 99%

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Herkenham

Kigar

2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…These parallel alterations are reminiscent of recent results showing that mood states and neurogenesis are typically associated with immune activation characterized by altered inflammatory cytokine expression [11]. Our team has previously shown that neonatal BCG vaccination improves neurogenesis and behavior through affecting the neuroimmune milieu in the brain [1]. However, the function roles of peripheral T lymphocytes in BCG-induced neurogenesis are unclear.…”

Section: Discussionmentioning

confidence: 65%

The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice

Song

Liu

et al. 2019

Preprint

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1.AbstractWe previously have reported that neonatal Bacillus Calmette-Guerin (BCG) vaccination improves neurogenesis and behavior in early life through affecting the neuroimmune milieu in the brain, but it is uncertain whether activation phenotypes and functional changes in T lymphocytes shape brain development. Here, we studied the effects of BCG vaccination via the adoptive transfer of T lymphocytes from the BALB/c wild-type mice into naive mice. Our results show that mice adoptive BCG-induced lymphocytes (BCG->naive mice) showed anxiolytic and antidepressant-like performance when completing an elevated plus maze (EPM) test. Meanwhile, BCG->naive mice possess more cell proliferation and newborn neurons than PBS->naive and nude mice in the hippocampus. IFN-γ and IL-4 levels in the serum of BCG->naive mice also increased, while TNF-α and IL-1β levels were reduced relative to those of PBS->naive and nude mice. We further found that BCG->naive mice showed different repartition of CD4+ and CD8+ T cell to naive (CD62L+ CD44low), effector memory (CD62L− CD44hi), central memory (CD62L+ CD44hi) and acute/activated effector (CD62L− CD44low) cells in the spleen. Importantly, the adoptive transfer of BCG-induced T lymphocytes infiltrated into the dura mater and brain parenchyma of the nude mice. Activation phenotypes and functional changes in T lymphocytes are very likely to affect the neuroimmune milieu in the brain, and alterations in ratios of splenic CD4+ and CD8+ memory T cells may affect the expression of correlative cytokines in the serum, accounting for our behavioral results. We conclude thus that the adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice. Our work shows that BCG vaccination improves hippocampal cell proliferation outcomes and behaviors, likely as a result of splenic effector/memory T lymphocytes regulating the neuroimmune niche in the brain.

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“…Air Liquide - Healthcare), in 100 μl of PBS. Three subcutaneous injection were performed at the tail region with a twenty-day interval between immunizations 9–10 (Fig. 2, Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Exogenous immune stimuli may also have positive or negative effect on the nervous system, depending on the nature and intensity of the immune response elicited 1–4,6 . Different studies, aiming to assess the effect of immune stimuli on brain function, reported i) the influence of maternal immune stimulation impairing the neurocognitive performance of offspring 8–9 , ii) both beneficial and harmful effects of neonate vaccination on neuronal plasticity and cognitive function in adulthood 10 , and iii) the damaging impact of inflammatory stimuli on the cognitive function of adult mice 11–12 . Some infections may also cause neurocognitive dysfunction in human and experimental models 13–27 .…”

Section: Introductionmentioning

confidence: 99%

Immune System Challenge Improves Cognitive-Behavioural Responses and Reverses Malaria-Induced Cognitive Impairment in Mice

Vieira

Ribeiro-Gomes

Almeida

et al. 2019

Preprint

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22The immune and nervous systems can be categorized as cognitive plastic systems for 23 their ability to know and recognize "real world objects", including microbes, and 24 because of their prerogative of constant self-reorganization as they live learning 25 experiences. After each antigenic or sensory occurrence, vertebrate organisms 26 experience changes in the cellular connections of their immune and nervous systems 27 altering their abilities and structures. Elements of the immune machinery are necessary 28 for neurocognitive function, and the pattern of the immune response triggered by 29 different stimuli may induce regulator or deregulator signals for the nervous functions. 30 Here we show, for the first time, that the immune modulation with anti-inflammatory 31 stimuli can positively regulate the behavior of healthy mice and mitigate the cognitive-32 behavioral deficits induced by a mild infection of C57BL/6 animals with Plasmodium 33 berghei ANKA.34 35 To address the effect of immune responses on locomotion and on long-term 87 habituation, mice were submitted to the open field task (OFT), with a training and a 88 test sessions, 24 hours apart, assessed in a well-established protocol 32 . Locomotion is 89 evaluated when mice access the open field arena for the first time. At the training 90 session, a high rate of locomotor activity is commonly observed. Surprisingly, Pool and 91 T1 immunized mice showed a reduced total OFT1 locomotion, when compared to non-92 immunized mice, and T2 immunized animals showed a clear trend towards a 93 decreased locomotion (Extended data, Fig1a) Commonly, after the training session, 94the exploratory behavior decreases, as the stress related to the novelty disappears, 95 and is significantly lower after 10 minutes of task performance 32,[48][49] . Control and all 96 immunized groups of mice presented a decreased locomotion in the test session 97 (OFT2) as compared to the training session (Extended data, Fig1a). These results 98 indicate that the immunization did not affect the long-term habituation memory 99 accessed 24 hours after training.100 101 Mice were then subjected to the novel object recognition test (NORT) in the same Open 102 Field arena. On the training session, a similar exploratory activity of both familiar (FO1 103 or FO2) objects is expected and was observed in all groups (Control, Pool, T1 and T2) 104 of mice (Fig.1a; Extended data, Fig.1c), exploring them for a mean of 25 seconds (data 105 not shown). Remarkably, as we hypothesized, the groups of mice immunized with the 106 Pool and T2 strategies presented significantly higher recognition memory performance 107 in relation to the control group of non-immunized mice during the test session (Fig.1c; 108 Extended data Fig.1e). These data indicate, for the first time, that an immune response 109 classically categorized as anti-inflammatory (induced by T2 stimuli) may enhance long-110 term recognition memory in healthy mice. 111 112Immunization of healthy mice did not influence their anxiety-like state 11...

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Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life

Cited by 43 publications

References 49 publications

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

Contributions of the adaptive immune system to mood regulation: Mechanisms and pathways of neuroimmune interactions

The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice

Immune System Challenge Improves Cognitive-Behavioural Responses and Reverses Malaria-Induced Cognitive Impairment in Mice

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