Impacts of age and environment on postnatal microglial activity: Consequences for cognitive function following early life adversity

被引:1
|
作者
Fanikos, Michaela [1 ]
Kohn, Skylar A. [1 ]
Stamato, Rebecca [1 ]
Brenhouse, Heather C. [1 ]
Gildawie, Kelsea R. [1 ]
机构
[1] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA
来源
PLOS ONE | 2024年 / 19卷 / 06期
关键词
PREFRONTAL CORTEX; MEMORY IMPAIRMENT; MATERNAL-CARE; STRESS; ADULT; BRAIN; CELL; NEUROGENESIS; DYSFUNCTION; REVEALS;
D O I
10.1371/journal.pone.0306022
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Early life adversity (ELA) increases the likelihood of later-life neuropsychiatric disorders and cognitive dysfunction. Importantly, ELA, neuropsychiatric disorders, and cognitive deficits all involve aberrant immune signaling. Microglia are the primary neuroimmune cells and regulate brain development. Microglia are particularly sensitive to early life insults, which can program their responses to future challenges. ELA in the form of maternal separation (MS) in rats alters later-life microglial morphology and the inflammatory profile of the prefrontal cortex, a region important for cognition. However, the role of microglial responses during MS in the development of later cognition is not known. Therefore, here we aimed to determine whether the presence of microglia during MS mediates long-term impacts on adult working memory. Clodronate liposomes were used to transiently deplete microglia from the brain, while empty liposomes were used as a control. We hypothesized that if microglia mediate the long-term impacts of ELA on working memory in adulthood, then depleting microglia during MS would prevent these deficits. Importantly, microglial function shifts throughout the neonatal period, so an exploratory investigation assessed whether depletion during the early versus late neonatal period had different effects on adult working memory. Surprisingly, empty liposome treatment during the early, but not late, postnatal period induced microglial activity changes that compounded with MS to impair working memory in females. In contrast, microglial depletion later in infancy impaired later life working memory in females, suggesting that microglial function during late infancy plays an important role in the development of cognitive function. Together, these findings suggest that microglia shift their sensitivity to early life insults across development. Our findings also highlight the potential for MS to impact some developmental processes only when compounded with additional neuroimmune challenges in a sex-dependent manner.
引用
收藏
页数:24
相关论文
共 50 条
  • [21] Heightened sensitivity to the caregiving environment during adolescence: implications for recovery following early-life adversity
    Colich, Natalie L.
    Sheridan, Margaret A.
    Humphreys, Kathryn L.
    Wade, Mark
    Tibu, Florin
    Nelson, Charles A.
    Zeanah, Charles H.
    Fox, Nathan A.
    McLaughlin, Katie A.
    JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY, 2021, 62 (08) : 937 - 948
  • [22] An investigation into early-life stress and cognitive function in older age
    Grainger, Sarah A.
    Crawford, John D.
    Kochan, Nicole A.
    Mather, Karen A.
    Chander, Russell J.
    Draper, Brian
    Brodaty, Henry
    Sachdev, Perminder S.
    Henry, Julie D.
    INTERNATIONAL PSYCHOGERIATRICS, 2020, 32 (11) : 1325 - 1329
  • [23] EARLY LIFE ADVERSITY, ALLOSTATIC LOAD, AND COGNITIVE FUNCTION AMONG MIDDLE-AGED AND OLDER ADULTS
    D'Amico, Danielle
    Amestoy, Maya
    Fiocco, Alexandra
    INNOVATION IN AGING, 2022, 6 : 604 - 604
  • [24] EFFECTS OF EARLY LIFE ADVERSITY ON IMMUNE FUNCTION AND COGNITIVE PERFORMANCE IN YOUTHS WITH AND WITHOUT EXPERIENCE OF PSYCHOTIC SYMPTOMS
    Holland, Jessica
    Dauvermann, Maria
    Morris, Derek
    Zammit, Stan
    Khandaker, Golam
    Donohoe, Gary
    SCHIZOPHRENIA BULLETIN, 2018, 44 : S325 - S325
  • [25] Early Life Adversity as a Moderator of Symptom Change following Selective Serotonin Reuptake Inhibitors and Cognitive Behavioral Therapy
    Gruhn, Meredith A.
    Luan Phan, K.
    Klumpp, Heide
    Ajilore, Olusola
    Gorka, Stephanie M.
    COGNITIVE THERAPY AND RESEARCH, 2021, 45 (02) : 343 - 354
  • [26] Early Life Adversity as a Moderator of Symptom Change following Selective Serotonin Reuptake Inhibitors and Cognitive Behavioral Therapy
    Meredith A. Gruhn
    K. Luan Phan
    Heide Klumpp
    Olusola Ajilore
    Stephanie M. Gorka
    Cognitive Therapy and Research, 2021, 45 : 343 - 354
  • [27] The mediating role of allostatic load in the relationship between early life adversity and cognitive function across the adult lifespan
    D'Amico, Danielle
    Amestoy, Maya E.
    Fiocco, Alexandra J.
    PSYCHONEUROENDOCRINOLOGY, 2022, 141
  • [28] Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure
    Raineki, Charlis
    Bodnar, Tamara S.
    Holman, Parker J.
    Baglot, Samantha L.
    Lan, Ni
    Weinberg, Joanne
    BRAIN BEHAVIOR AND IMMUNITY, 2017, 66 : 210 - 220
  • [29] Weaning and postnatal age influence the early time course and nature of intestinal mast cell activation and mucosal inflammation in a porcine model of early life adversity
    Wilson, Neco
    Li, Yihang
    Rajput, Mrigendra
    Thelen, Kyan
    Kerr, Katie
    Moeser, Adam J.
    JOURNAL OF IMMUNOLOGY, 2019, 202 (01):
  • [30] Early-life home environment and child cognitive function: A meta-analysis
    Han, Jing
    Cui, Naixue
    Lyu, Pingping
    Li, Yang
    PERSONALITY AND INDIVIDUAL DIFFERENCES, 2023, 200