The effects of a probiotic formulation (Lactobacillus rhamnosus and L. helveticus) on developmental trajectories of emotional learning in stressed infant rats.

Recently, scientific interest in the brain-gut axis has grown dramatically, particularly with respect to the link between gastrointestinal and psychiatric dysfunction. However, the role of gut function in early emotional dysregulation is yet to be examined, despite the prevalence and treatment resistance of early-onset psychiatric disorders. The present studies utilized a developmental rodent model of early-life stress (ELS) to explore this gap. Rats were exposed to maternal separation (MS) on postnatal days 2-14. Throughout MS, dams received either vehicle or a probiotic formulation (previously shown to reduce gastrointestinal dysfunction) in their drinking water. Replicating past research, untreated MS infants exhibited an adult-like profile of long-lasting fear memories and fear relapse following extinction. In contrast, probiotic-exposed MS infants exhibited age-appropriate infantile amnesia and resistance to relapse. These effects were not mediated by changes in pups' or dams' anxiety at the time of training, nor by maternal responsiveness. Overall, probiotics acted as an effective and non-invasive treatment to restore normal developmental trajectories of emotion-related behaviors in infant rats exposed to ELS. These results provide promising initial evidence for this novel approach to reduce the risk of mental health problems in vulnerable individuals. Future studies are needed to test this treatment in humans exposed to ELS and to elucidate mechanisms for the observed behavioral changes

Acute early-life stress results in premature emergence of adult-like fear retention and extinction relapse in infant rats

Recent studies have shown that chronic early life stress results in precocious expression of the adult-like phenotype of fear retention and inhibition. However, it is unknown whether the experience of acute early trauma has the same effects as exposure to chronic early stress. In the present study, a 24-hr period of maternal deprivation on postnatal day (P) 9 was used as an acute early life stressor. In infancy (P16-17), maternally deprived and standard-reared rats were conditioned to fear a noise paired with shock. In Experiments 1 and 2, fear to the noise was then extinguished before rats were tested for context-mediated fear renewal or stress-induced fear reinstatement. In Experiments 3a and 3b, conditioned rats were tested for fear retention 1, 7, or 14 days after training. Whereas standard-reared infants exhibited relapse-resistant extinction and infantile amnesia (i.e., behaviors typical of their age), maternally deprived infants exhibited the renewal and reinstatement effects (i.e., relapse-prone extinction) and showed good retention of fear over the 7- and 14-day intervals (i.e., infantile amnesia was reduced). In other words, similar to rats exposed to chronic early life stress, rats exposed to acute early stress expressed an adult-like profile of fear retention and inhibition during infancy. These findings suggest that similar mechanisms might be involved in the effects of acute and chronic stress on emotional development, and may have implications for our understanding and treatment of emotional disorders associated with early adversity

Treating generational stress: effect of paternal stress on development of memory and extinction in offspring is reversed by probiotic treatment

Early-life adversity is a potent risk factor for mental-health disorders in exposed individuals, and effects of adversity are exhibited across generations. Such adversities are also associated with poor gastrointestinal outcomes. In addition, emerging evidence suggests that microbiota-gut-brain interactions may mediate the effects of early-life stress on psychological dysfunction. In the present study, we administered an early-life stressor (i.e., maternal separation) to infant male rats, and we investigated the effects of this stressor on conditioned aversive reactions in the rats' subsequent infant male offspring. We demonstrated, for the first time, longer-lasting aversive associations and greater relapse after extinction in the offspring (F1 generation) of rats exposed to maternal separation (F0 generation), compared with the offspring of rats not exposed to maternal separation. These generational effects were reversed by probiotic supplementation, which was effective as both an active treatment when administered to infant F1 rats and as a prophylactic when administered to F0 fathers before conception (i.e., in fathers' infancy). These findings have high clinical relevance in the identification of early-emerging putative risk phenotypes across generations and of potential therapies to ameliorate such generational effects

The lasting impact of early-life adversity on individuals and their descendants: potential mechanisms and hope for intervention

The adverse effects of early-life stress are pervasive, with well-established mental and physical health consequences for exposed individuals. The impact of early adverse experiences is also highly persistent, with documented increases in risk for mental illness across the life span that are accompanied by stable alterations in neural function and hormonal responses to stress. Here, we review some of these 'stress phenotypes', with a focus on intermediary factors that may signal risk for long-term mental health outcomes, such as altered development of the fear regulation system. Intriguingly, recent research suggests that such stress phenotypes may persist even beyond the life span of the individuals, with consequences for their offspring and grand-offspring. Phenotypic characteristics may be transmitted to future generations via either the matriline or the patriline, a phenomenon that has been demonstrated in both human and animal studies. In this review, we highlight behavioral and epigenetic factors that may contribute to this multigenerational transmission and discuss the potential of various treatment approaches that may halt the cycle of stress phenotypes

It’s Time to Rebrand "Mommy Brain"

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Acute early-life stress results in premature emergence of adult-like fear retention and extinction relapse in infant rats

Recent studies have shown that chronic early life stress results in precocious expression of the adult-like phenotype of fear retention and inhibition. However, it is unknown whether the experience of acute early trauma has the same effects as exposure to chronic early stress. In the present study, a 24-hr period of maternal deprivation on postnatal day (P) 9 was used as an acute early life stressor. In infancy (P16-17), maternally deprived and standard-reared rats were conditioned to fear a noise paired with shock. In Experiments 1 and 2, fear to the noise was then extinguished before rats were tested for context-mediated fear renewal or stress-induced fear reinstatement. In Experiments 3a and 3b, conditioned rats were tested for fear retention 1, 7, or 14 days after training. Whereas standard-reared infants exhibited relapse-resistant extinction and infantile amnesia (i.e., behaviors typical of their age), maternally deprived infants exhibited the renewal and reinstatement effects (i.e., relapse-prone extinction) and showed good retention of fear over the 7- and 14-day intervals (i.e., infantile amnesia was reduced). In other words, similar to rats exposed to chronic early life stress, rats exposed to acute early stress expressed an adult-like profile of fear retention and inhibition during infancy. These findings suggest that similar mechanisms might be involved in the effects of acute and chronic stress on emotional development, and may have implications for our understanding and treatment of emotional disorders associated with early adversity

Treating generational stress: effect of paternal stress on development of memory and extinction in offspring is reversed by probiotic treatment

Early-life adversity is a potent risk factor for mental-health disorders in exposed individuals, and effects of adversity are exhibited across generations. Such adversities are also associated with poor gastrointestinal outcomes. In addition, emerging evidence suggests that microbiota-gut-brain interactions may mediate the effects of early-life stress on psychological dysfunction. In the present study, we administered an early-life stressor (i.e., maternal separation) to infant male rats, and we investigated the effects of this stressor on conditioned aversive reactions in the rats\u27 subsequent infant male offspring. We demonstrated, for the first time, longer-lasting aversive associations and greater relapse after extinction in the offspring (F1 generation) of rats exposed to maternal separation (F0 generation), compared with the offspring of rats not exposed to maternal separation. These generational effects were reversed by probiotic supplementation, which was effective as both an active treatment when administered to infant F1 rats and as a prophylactic when administered to F0 fathers before conception (i.e., in fathers\u27 infancy). These findings have high clinical relevance in the identification of early-emerging putative risk phenotypes across generations and of potential therapies to ameliorate such generational effects

The lasting impact of early-life adversity on individuals and their descendants: potential mechanisms and hope for intervention

The adverse effects of early-life stress are pervasive, with well-established mental and physical health consequences for exposed individuals. The impact of early adverse experiences is also highly persistent, with documented increases in risk for mental illness across the life span that are accompanied by stable alterations in neural function and hormonal responses to stress. Here, we review some of these \u27stress phenotypes\u27, with a focus on intermediary factors that may signal risk for long-term mental health outcomes, such as altered development of the fear regulation system. Intriguingly, recent research suggests that such stress phenotypes may persist even beyond the life span of the individuals, with consequences for their offspring and grand-offspring. Phenotypic characteristics may be transmitted to future generations via either the matriline or the patriline, a phenomenon that has been demonstrated in both human and animal studies. In this review, we highlight behavioral and epigenetic factors that may contribute to this multigenerational transmission and discuss the potential of various treatment approaches that may halt the cycle of stress phenotypes