Maternal stress induces adult reduced REM sleep and melatonin level

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Developmental Neurobiology (Impact Factor: 3.37). 05/2012; 72(5):677-87. DOI: 10.1002/dneu.20961
Source: PubMed


We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Adult male Sprague-Dawley rats were treated with either MD or MC procedures for 10 days starting at postnatal day 4. At 3 months of age, sleep was recorded for 48 h in one set of MD and MC rats, while another set of MD and MC rats was measured for locomotor activity (under LD = 12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Compared to the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared to the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein.

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    • "The preclinical literature describes some changes in sleep architecture after early environmental factors. Although the studies are scarce and the findings are divergent, long maternal separation (LMS) in rats is reported to change total sleep time (decrease or increase) and increase wakefulness compared to non-handled, handled and brief maternally separated (BMS) conditions [11]–[13]. "
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    ABSTRACT: Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.
    PLoS ONE 07/2013; 8(7):e69923. DOI:10.1371/journal.pone.0069923 · 3.23 Impact Factor
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    • "Additionally, environmental factors can influence melatonin synthesis. For instance, maternal stress was shown to result in reduced melatonin levels (Feng et al., 2012) as well as light pollution (Reiter et al., 2006; Falchi et al., 2011). Interestingly, Zn 2+ -deficiency has an effect on various hormones such as melatonin. "
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    ABSTRACT: Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.
    Frontiers in Psychiatry 11/2012; 3:118. DOI:10.3389/fpsyt.2012.00118
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    ABSTRACT: Maternal separation (MS) induces a series of changes in rats' behavior; among them a reduction in spontaneous sleep. One potentially impaired system is the endocannabinoid system (eCBs), since it contributes to generate sleep. To investigate if there are situations early in life that affect the eCBs, which would contribute to make rats vulnerable to suffering insomnia, we studied the rodent model of MS. Rats were separated from their mothers for 3h-periods daily, from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult rats), they were implanted with electrodes to record the sleep-waking cycle (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R), OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1 receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the consequent increase in waking (W) as compared to NMS siblings. OLE normalized the SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R expression and OLE improves sleep in adult rats.
    Pharmacology Biochemistry and Behavior 09/2012; 103(2):308-312. DOI:10.1016/j.pbb.2012.08.028 · 2.78 Impact Factor
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