Article

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.

Download full-text

Full-text

Available from: Raz Yirmiya
  • Source
    • "The pathways whereby this effect occurs are opaque; changes in appetite and energy balance may have negative effects on cognition because interference in the metabolism of glucose may lead to insulin resist- ance[84], abnormal neurotransmitter turnover, mitochondrial dysfunction, and energy deficits, as well as changes in neural plasticity[85]. Finally, psychotropic agents may have a similar effect on the immune system and, consequently, on cognitive performance[86,87]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Discussion: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.
    Full-text · Article · Dec 2016 · BMC Medicine
  • Source
    • "Neural stem/precursor cells can be intravenously administered and then migrate into brain damaged areas and induce functional recovery [5]. Neurogenesis, highly sensitive to a hostile microenvironment as the result of stress and aging, is critical for the maintenance of normal learning and memory [6]. It has been reported that there existed increasing number of immature neuronal cells in the brains of patients with AD, compared with the brains of age-matched control subjects [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease, one of the neurodegenerative diseases, shows the progressive senescence of neural progenitor/stem cells. N-Stearoyl-L-tyrosine (NsTyr) showed neuroprotective effect against chronic brain ischemia in previous reports. In the present study, we find the antisenescent effects of NsTyr-2K in NSPCs induced by A β 1 – 42 in vitro . Cell viability of NSPCs was evaluated by CCK8 assay; SA- β -gal staining was used to evaluate senescence of NSPCs. CB receptors were detected by immunohistochemistry in NSPCs. AM251 or AM630 was used to offset the anti-senescence effects afforded by NsTyr-2K. The positive rate of SA- β -gal staining was significantly increased in NSPCs after incubation with A β 1 – 42 for 9 days. CB receptors were found on the surface of NSPCs. The expression level of CB1 receptors was significantly decreased in NSPCs after incubation with A β 1 – 42 . This phenomenon was reversed dose-dependently by NsTyr-2K. NsTyr-2K attenuated A β 1 – 42 induced NSPCs senescence dose-dependently, and its antisenescence effect was completely abolished by AM630. A β 1 – 42 dose-dependently increased the prosenescence molecules p16 and Rb. Their expression was inhibited by NsTyr-2K dose-dependently and blocked by AM630 in NSPCs. These results suggest that NsTyr-2K can alleviate the senescence of NSPCs induced by A β 1 – 42 via CB2 receptor.
    Full-text · Article · Jan 2016 · Stem cell International
  • Source
    • "It is characterized by the brain synthesis and release of pro-inflammatory mediators known to control neuronal function (Cunningham and Sanderson, 2008;Delpech et al., 2015b;Hanisch and Kettenmann, 2007;Pascual et al., 2012;Yirmiya and Goshen, 2011). Pro-inflammatory factors including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) have been directly linked to impaired neuronal plasticity in various animal models (Delpech et al., 2015b;Yirmiya and Goshen, 2011). Microglia are the resident macrophages of the brain, and constitute the first line of immune defense (Ransohoff and Cardona, 2010). "

    Full-text · Article · Jan 2016
Show more