Maternal separation induces retinal and peripheral blood mononuclear cell alterations across the lifespan of female rats

Grigoruta, Mariana; Chavez-Solano, Marbella; Varela-Ramı́rez, Armando; Sierra-Fonseca, Jorge A.; Orozco‐Lucero, Ernesto; Hamdan, Jameel N; Gosselink, K. L.; Martínez‐Martínez, Alejandro

doi:10.1016/j.brainres.2020.147117

Cited by 7 publications

(4 citation statements)

References 66 publications

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“…Numerous animal studies using ELS models offer results suggesting increased OXS markers and reduced antioxidant activity. For example, a study on the impact of MS across three stages of the lifespan (adolescent, adult, and aged) on the mitochondrial activity in peripheral blood mononuclear cells (PBMCs) in rats showed disrupted cell cycle and longterm increases in mitochondrial activity, as well as increased sensitivity to H 2 O 2 -induced oxidative stress in vitro in adolescent and adult rats [103]. Another study on the effects of MS on the oxidative status in adult mice, showed increased plasma TBARS and decreased catalase activity in the hippocampus [104].…”

Section: Oxs In Animal Models Of Elsmentioning

confidence: 99%

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

2021

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Traumatic stress may chronically affect master homeostatic systems at the crossroads of peripheral and central susceptibility pathways and lead to the biological embedment of trauma-related allostatic trajectories through neurobiological alterations even decades later. Lately, there has been an exponential knowledge growth concerning the effect of traumatic stress on oxidative components and redox-state homeostasis. This extensive review encompasses a detailed description of the oxidative cascade components along with their physiological and pathophysiological functions and a systematic presentation of both preclinical and clinical, genetic and epigenetic human findings on trauma-related oxidative stress (OXS), followed by a substantial synthesis of the involved oxidative cascades into specific and functional, trauma-related pathways. The bulk of the evidence suggests an imbalance of pro-/anti-oxidative mechanisms under conditions of traumatic stress, respectively leading to a systemic oxidative dysregulation accompanied by toxic oxidation byproducts. Yet, there is substantial heterogeneity in findings probably relative to confounding, trauma-related parameters, as well as to the equivocal directionality of not only the involved oxidative mechanisms but other homeostatic ones. Accordingly, we also discuss the trauma-related OXS findings within the broader spectrum of systemic interactions with other major influencing systems, such as inflammation, the hypothalamic-pituitary-adrenal axis, and the circadian system. We intend to demonstrate the inherent complexity of all the systems involved, but also put forth associated caveats in the implementation and interpretation of OXS findings in trauma-related research and promote their comprehension within a broader context.

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Section: Oxs In Animal Models Of Elsmentioning

confidence: 99%

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

2021

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“…Neonatal Wistar rats were subjected to MatSep according to previously described protocols (Huot et al, 2002;Kalinichev et al, 2002), with some modifications (Grigoruta et al, 2020). During post-natal days (PND) 2-14, dams and pups were removed from their home cage for 3 h daily beginning at 0800 h. Dams were placed in a holding cage under an extraction hood, while the pups were moved to a different cage containing surgical bedding and placed on top of a circulating water bath set at 37 • C. Once the separation period was over, dams and pups were returned to their home cage.…”

Section: Early Life Stressmentioning

confidence: 99%

“…In rodents, neonatal MatSep is a well-established model for the study of ELS. MatSep is known to influence brain development, induce long–lasting neurochemical changes, alter neuroimmunological and stress responses, and enhance vulnerability to a variety of neurological disorders such as depression, addiction, and neurodegeneration (Aisa et al, 2007 ; Nishi et al, 2014 ; Gracia-Rubio et al, 2016 ; Hui et al, 2017 ; Grigoruta et al, 2020 ). A previous study showed that MatSep can influence autophagy in adult rat hippocampus and prefrontal cortex (Liu et al, 2018 ), and another study demonstrated that levels of FKBP5, a co-chaperone protein involved in proteostasis, can modulate the effects of MatSep on anxiety-like behavior in adult mice (Criado-Marrero et al, 2019 ), thus supporting the notion that this ELS paradigm has the ability to modify proteostasis responses later in life.…”

Section: Introductionmentioning

confidence: 99%

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Sierra-Fonseca

Hamdan

Cohen

et al. 2021

Front. Mol. Neurosci.

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Exposure to early-life stress (ELS) can persistently modify neuronal circuits and functions, and contribute to the expression of misfolded and aggregated proteins that are hallmarks of several neurodegenerative diseases. The healthy brain is able to clear dysfunctional proteins through the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP). Accumulating evidence indicates that impairment of these pathways contributes to enhanced protein aggregation and neurodegeneration. While stress is a known precipitant of neurological decline, few specific mechanistic links underlying this relationship have been identified. We hypothesized that neonatal maternal separation (MatSep), a well-established model of ELS, has the ability to alter the levels of UPS and ALP components in the brain, and thus has the potential to disrupt proteostasis. The expression of proteostasis-associated protein markers was evaluated by immunoblotting in the hippocampus and cortex of adult Wistar rats that were previously subjected to MatSep. We observed multiple sex- and MatSep-specific changes in the expression of proteins in the ALP, mitophagy, and UPS pathways, particularly in the hippocampus of adult animals. In contrast, MatSep had limited influence on proteostasis marker expression in the cortex of adult animals. Our results indicate that MatSep can selectively modify the intracellular protein degradation machinery in ways that may impact the development and progression of neurodegenerative disease.

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“…MS evokes dysregulation of mitochondrial sirtuins within the PFC that persist well into middle-aged life (15 months) ( Pusalkar et al, 2016 ), and robust decreases in mitochondrial mass in the periphery, namely the muscle, noted 8 months post the cessation of MS ( Ghosh et al, 2016 ). Further, MS animals exhibit enhanced sensitivity to oxidative stress in peripheral mononuclear cells, noted until 18 months of age, and also reported in gut epithelial cells when examined in adulthood (2 months) in MS animals ( Grigoruta et al, 2020 ; Khorjahani et al, 2020 ). Impaired calcium homeostasis, enhanced ROS and a decrease in oxygen consumption rate (OCR) or ATP production is also reported in the PFC, raphe and hippocampus of adult (2–6 month) MS animals, suggestive of a broad mitochondrial dysfunction in multiple systems ( Della et al, 2013 ; Amini-Khoei et al, 2017 ; Masrour et al, 2018 ; Nold et al, 2019 ).…”

Section: Early Adversity Mitochondrial Dysfunction and Oxidative Stressmentioning

confidence: 54%

Early Adversity and Accelerated Brain Aging: A Mini-Review

Chaudhari

Singla

Vaidya

2022

Front. Mol. Neurosci.

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Early adversity is an important risk factor that influences brain aging. Diverse animal models of early adversity, including gestational stress and postnatal paradigms disrupting dam-pup interactions evoke not only persistent neuroendocrine dysfunction and anxio-depressive behaviors, but also perturb the trajectory of healthy brain aging. The process of brain aging is thought to involve hallmark features such as mitochondrial dysfunction and oxidative stress, evoking impairments in neuronal bioenergetics. Furthermore, brain aging is associated with disrupted proteostasis, progressively defective epigenetic and DNA repair mechanisms, the build-up of neuroinflammatory states, thus cumulatively driving cellular senescence, neuronal and cognitive decline. Early adversity is hypothesized to evoke an “allostatic load” via an influence on several of the key physiological processes that define the trajectory of healthy brain aging. In this review we discuss the evidence that animal models of early adversity impinge on fundamental mechanisms of brain aging, setting up a substratum that can accelerate and compromise the time-line and nature of brain aging, and increase risk for aging-associated neuropathologies.

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Maternal separation induces retinal and peripheral blood mononuclear cell alterations across the lifespan of female rats

Cited by 7 publications

References 66 publications

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

Neonatal Maternal Separation Modifies Proteostasis Marker Expression in the Adult Hippocampus

Early Adversity and Accelerated Brain Aging: A Mini-Review

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