Mycobacterium vaccae immunization protects aged rats from surgery-elicited neuroinflammation and cognitive dysfunction

NEUROBIOLOGY OF AGING

卷:71

Article

Fonken, Laura K.^1,2  Frank, Matthew G.¹  D'Angelo, Heather M.¹  Heinze, Jared D.^3,4  Watkins, Linda R.¹  Lowry, Christopher A.^3,4  Maier, Steven F.¹ 

[1] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[2] Univ Texas Austin, Div Pharmacol & Toxicol, 107 W Dean Keeton,BME 3-510C, Austin, TX 78712 USA

[3] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA

[4] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA

关键词: Aging;    Microglia;    Neuroimmune;    POCD;    T cells;    Surgical stress;   

DOI  :  10.1016/j.neurobiolaging.2018.07.012

来源: Elsevier

【 摘 要 】

Aging is a major risk factor for developing postoperative cognitive dysfunction. Neuroinflammatory processes, which can play a causal role in the etiology of postoperative cognitive dysfunction, are potentiated or primed as a function of aging. Here we explored whether exposure to a microorganism with immunoregulatory and anti-inflammatory properties, Mycobacterium vaccae NCTC 11659 (M. vaccae), could ameliorate age-associated neuroinflammatory priming. Aged (24 months) and adult (3 months) male F344XBN rats were immunized with heat-killed M. vaccae (3 injections, once per week) before undergoing a laparotomy or anesthesia control procedure. Aged, but not young rats, showed postoperative learning/memory deficits in a fear-conditioning paradigm. Importantly, M. vaccae immunization protected aged rats from these surgery-induced cognitive impairments. M. vaccae immunization also shifted the aged proinflammatory hippocampal microenvironment toward an anti-inflammatory phenotype. Furthermore, M. vaccae immunization reduced age-related hyperinflammatory responses in isolated hippocampal microglia. Overall, our novel data suggest that M. vaccae can induce an anti-inflammatory milieu in the aged brain and thus mitigate the neuroinflammatory and cognitive impairments induced by surgery. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

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