Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25: 181-213

Department of Psychology, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Brain Behavior and Immunity (Impact Factor: 5.89). 10/2010; 25(2):181-213. DOI: 10.1016/j.bbi.2010.10.015
Source: PubMed

ABSTRACT Over the past two decades it became evident that the immune system plays a central role in modulating learning, memory and neural plasticity. Under normal quiescent conditions, immune mechanisms are activated by environmental/psychological stimuli and positively regulate the remodeling of neural circuits, promoting memory consolidation, hippocampal long-term potentiation (LTP) and neurogenesis. These beneficial effects of the immune system are mediated by complex interactions among brain cells with immune functions (particularly microglia and astrocytes), peripheral immune cells (particularly T cells and macrophages), neurons, and neural precursor cells. These interactions involve the responsiveness of non-neuronal cells to classical neurotransmitters (e.g., glutamate and monoamines) and hormones (e.g., glucocorticoids), as well as the secretion and responsiveness of neurons and glia to low levels of inflammatory cytokines, such as interleukin (IL)-1, IL-6, and TNFα, as well as other mediators, such as prostaglandins and neurotrophins. In conditions under which the immune system is strongly activated by infection or injury, as well as by severe or chronic stressful conditions, glia and other brain immune cells change their morphology and functioning and secrete high levels of pro-inflammatory cytokines and prostaglandins. The production of these inflammatory mediators disrupts the delicate balance needed for the neurophysiological actions of immune processes and produces direct detrimental effects on memory, neural plasticity and neurogenesis. These effects are mediated by inflammation-induced neuronal hyper-excitability and adrenocortical stimulation, followed by reduced production of neurotrophins and other plasticity-related molecules, facilitating many forms of neuropathology associated with normal aging as well as neurodegenerative and neuropsychiatric diseases.

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    • "Evidence supports infl ammatory alterations in major depressive disorder (MDD; Dowlati et al. 2010; Valkanova et al. 2013), schizophrenia (Potvin et al. 2008) and bipolar disorder (Modabbernia et al. 2013). Cytokines are important for brain development , and healthy brain function by supporting neuronal integrity, neurogenesis, and synaptic remodelling (Yirmiya and Goshen 2011), neurocircuitry and neurotransmitters to produce behavioural alterations (Haroon et al. 2012). The so-called " cytokine-induced sickness behaviour " (i.e., lethargy , depression, failure to concentrate, anorexia, sleep disturbances, decreased personal hygiene and social withdrawal) was shown to be mediated by proinfl ammatory cytokines IL-1, IL-6, and TNF-α (Dantzer et al. 2008). "
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    • "It is possible that the alterations on IL-1 levels are responsible for the increase in weight of the placenta found in our previous works (Cruttenden et al., 2008; Dorce et al., 2014). Regarding IFN-g, we know that, along with other components of the immune system, it is involved in the process of neurogenesis (Yirmiya and Goshen, 2011). Under normal conditions, the microglia is activated by IFN-g, a cytokine produced by T cells, which induces cell differentiation (Butovsky et al., 2006). "
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    • "2001 ) . Rodent studies have demonstrated physiological roles of cytokines in memory and learning , including long - term potentiation , synaptic plasticity and neurogenesis ( reviewed by Yirmiya and Goshen 2011 ) . Mild systemic in - flammation has been reported to produce impairments in spa - tial memory in humans via its action on glucose metabolism in the medial temporal lobe ( Harrison et al . "
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