Strain-specific cognitive deficits in adult mice exposed to early life stress.

Injuries that occur early in life are often at the root of adult illness. Neonatal maternal separation (NMS) is a form of early life stress that has persistent and sex-specific effects on the development of neural networks, including those that regulate breathing. The release of stress hormones during a critical period of development contributes to the deleterious consequences of NMS, but the role of increased corticosterone (CORT) in NMS-induced respiratory disturbance is unknown. Because erythropoietin (EPO) is a potent neuroprotectant that prevents conditions associated with hyperactivation of the stress neuroaxis in a sex-specific manner, we hypothesized that EPO reduces the sex-specific alteration of respiratory regulation induced by NMS in adult mice. Animals were either raised under standard conditions (controls) or exposed to NMS 3 h/day from postnatal days 3–12. We tested the efficacy of EPO in preventing the effects of NMS by comparing wild-type mice with transgenic mice that overexpress EPO only in the brain (Tg21). In 7-days-old pups, NMS augmented CORT levels ~2.5-fold by comparison with controls but only in males; this response was reduced in Tg21 mice. Respiratory function was assessed using whole-body plethysmography. Apneas were detected during sleep; the responsiveness to stimuli was measured by exposing mice to hypoxia (10% O2; 15 min) and hypercapnia (5% CO2; 10 min). In wild-type, NMS increased the number of apneas and the hypercapnic ventilatory response (HcVR) only in males; with no effect on Tg21. In wild-type males, the incidence of apneas was positively correlated with HcVR and inversely related to the tachypneic response to hypoxia. We conclude that neural EPO reduces early life stress-induced respiratory disturbances observed in males.

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Early-life stress-induced anxiety-related behavior in adult mice partially requires forebrain corticotropin-releasing hormone receptor 1

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2012.08148.x ◽

2012 ◽

Vol 36 (3) ◽

pp. 2360-2367 ◽

Cited By ~ 56

Author(s):

Xiao-Dong Wang ◽

Christiana Labermaier ◽

Florian Holsboer ◽

Wolfgang Wurst ◽

Jan M. Deussing ◽

...

Keyword(s):

Hormone Receptor ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Adult Mice

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The impact of early-life stress on the expression of HPA-associated genes in the adult murine brain

Behaviour ◽

10.1163/1568539x-00003482 ◽

2018 ◽

Vol 155 (2-3) ◽

pp. 181-203 ◽

Cited By ~ 7

Author(s):

V.V. Reshetnikov ◽

A.A. Studenikina ◽

J.A. Ryabushkina ◽

T.I. Merkulova ◽

N.P. Bondar

Keyword(s):

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Long Term Memory ◽

Adult Mice ◽

Specific Manner ◽

Behavioural Phenotypes ◽

The Impact

Abstract Early life is an important period for the development of the nervous system and for the programming of behavioural phenotypes in adulthood. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 h/day, maternal separation (MS)) and brief separation (for 15 min/day, handling (HD)). We analysed the effects of early-life stress on behaviour and the expression of HPA-associated genes in the hypothalamus, hippocampus, and frontal cortex of male mice. Adult mice in the MS group demonstrated reduced locomotor activity and deficiencies in spatial long-term memory, while the HD showed no significant changes. Additionally, early-life MS resulted in reduced hippocampal Crhr1 mRNA, increased MR/GR mRNA in the hippocampus and hypothalamus. Both groups, HD and MS, showed increased Avp mRNA in the hypothalamus. Thus, prolonged maternal separation but not brief leads to adverse behavioural changes and influences the expression of HPA-associated genes in a brain region-specific manner.

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