32 research outputs found
MiRNA-34 and stress response
Psychiatric disorders are known to result from a strong interaction between genetic predisposition and environmental factors, mainly exposure to stressful events. Environmental events can modulate genes expression, possibly via epigenetic mechanisms, and affect onset/expression of a disease [1]. Epigenetic mechanisms include, among others, post-transcriptional regulation by non-coding RNAs such as microRNAs (miRNAs). MiRNAs are small non-coding RNAs predicted to regulate hundreds of targets and to be engaged in every biological process [2]. Thanks to their ability to fine-tune gene expression, miRNAs can control gene expression patterns favoring organismâs adaptation to internal and
environmental (external) factors [3], such as stressful events
Animal models of compulsive eating behavior
In industrialized nations, overeating is a significant problem leading to overweight, obesity, and a host of related disorders; the increase in these disorders has prompted a significant amount of research aimed at understanding their etiology. Eating disorders are multifactorial conditions involving genetic, metabolic, environmental, and behavioral factors. Considering that compulsive eating in the face of adverse consequences characterizes some eating disorders, similar to the way in which compulsive drug intake characterizes drug-addiction, it might be considered an addiction in its own right. Moreover, numerous review articles have recently drawn a connection between the neural circuits activated in the seeking/intake of palatable food and drugs of abuse. Based on this observation, âfood addictionâ has emerged as an area of intense scientific research and accumulating evidence suggests it is possible to model some aspects of food addiction in animals. The development of well-characterized animal models would advance our understanding of the etiologic neural factors involved in eating disorders, such as compulsive overeating, and it would permit to propose targeted pharmacological therapies. However, to date, little evidence has been reported of continued food seeking and intake despite its harmful consequences in rats and mice
Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety
Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and
environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters,
a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to
stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34
family have been suggested to regulate synaptic plasticity and neurotransmission processes, which
mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the
miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic
and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover,
we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the
BLA of stress-exposed TKO mice.
We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction.
Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and
no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential
GRM7, 5-HT2C, and CRFR1 mRNA expressionwas noted in the mpFC and BLA between TKO andWT
mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and
neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity
Mouse model of panic disorder: Vulnerability to early environmental instability is strain-dependent.
AbstractEarly life experiences and genetic background shape phenotypic variation. Several mouse models based on early treatments have evaluated shortâ and longâterm phenotypic alterations and explored their molecular mechanisms. The instability of maternal cues was used to model human separation anxiety in outbred mice, one of the etiopathogenetic factors that predict panic disorder (PD). Application of the repeated crossâfostering (RCF) protocol to inbred strains (C57 and DBA) allowed us to measure differential responses to the same experimental manipulation. Ultrasounds emitted during isolation indicated that after RCF, pups from both strains lose their ability to be comforted by nest cues, but the frequency modulation of separation calls increased in RCFâC57 and decreased in RCFâDBA mice. No strainâspecific difference in olfactory ability explained these responses in RCFâexposed mice. Rather, disruption of the infantâmother bond may differentially affect separation calls in the two strains. Moreover, the RCFâassociated increased respiratory response to hypercapniaâan endophenotype of human PD documented among mice outbred strainsâwas replicated in the C57 strain only. We suggest that RCFâinduced instability of the early environment affects emotionality and respiratory physiology differentially, depending on pups' genetic background. These strainâspecific responses provide a lead to understand differential vulnerability to emotional disorders
Correction to: MicroRNA-34 Contributes to the Stress-related Behavior and Affects 5-HT Prefrontal/GABA Amygdalar System through Regulation of Corticotropin-releasing Factor Receptor 1
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Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice
Early life experiences that affect the attachment bond formation can alter developmental trajectories and result in pathological outcomes in a sex-related manner. However, the molecular basis of sex differences is quite unknown. The dopaminergic system originating from the ventral tegmental area has been proposed to be a key mediator of this process.Here we exploited a murine model of early adversity (Repeated Cross Fostering, RCF) to test how interfering with the attachment bond formation affects the VTA-related functions in a sex-specific manner.Through a comprehensive behavioral screening, within the NiH RDoC framework, and by next-generation RNA-Seq experiments, we analyzed the long-lasting effect of RCF on behavioral and transcriptional profiles related to the VTA, across two different inbred strains of mouse in both sexes.We found that RCF impacted to an extremely greater extent VTA-related behaviors in females than in males and this result mirrored the transcriptional alterations in the VTA that were almost exclusively observed in females. The sexual dimorphism was conserved across two different inbred strains in spite of their divergent long lasting consequences of RCF exposure.Our data suggest that to be female primes a sub-set of genes to respond to early environmental perturbations.This is, to the best of our knowledge, the first evidence of an almost exclusive effect of early life experiences on females, thus mirroring the extremely stronger impact of precocious aversive events reported in clinical studies in women
Long-term effects of early environment on the brain: Lesson from rodent models
The postnatal period is characterized by extensive neuronal plasticity, synaptic organization, and remod-eling. High neuroplasticity renders the brain sensitive to the remodeling effects induced by environmentalfactors, such as exposure to adversity, which can imprint neurochemical, neuroendocrine, morphological,and behavioral changes.Early experiences that influence developmental trajectories during maturation of the brain can have awide range of long-lasting effects, modulating stress-coping strategies in adult life and inducing vulner-ability or resilience to psychopathologies, depending on the gene Ă later experience interplay.Future studies will clarify how manipulation of the early environment induces these effects acting ongenetic and epigenetic factors
Linking drug and food addiction: an overview of the shared neural circuits and behavioral phenotype
Despite a lack of agreement on its definition and inclusion as a specific diagnosable disturbance, the food addiction construct is supported by several neurobiological and behavioral clinical and preclinical findings. Recognizing food addiction is critical to understanding how and why it manifests. In this overview, we focused on those as follows: 1. the hyperpalatable food effects in food addiction development; 2. specific brain regions involved in both food and drug addiction; and 3. animal models highlighting commonalities between substance use disorders and food addiction. Although results collected through animal studies emerged from protocols differing in several ways, they clearly highlight commonalities in behavioral manifestations and neurobiological alterations between substance use disorders and food addiction characteristics. To develop improved food addiction models, this heterogeneity should be acknowledged and embraced so that research can systematically investigate the role of specific variables in the development of the different behavioral features of addiction-like behavior in preclinical models
Food seeking in spite of harmful consequences
In industrialized nations, overeating is a significant problem leading to overweight, obesity, and a host of related disorders; the increase in these disorders has prompted a significant amount of research aimed at understanding their etiology. Eating disorders are multifactorial conditions involving genetic, metabolic, environmental, and behavioral factors. Considering that compulsive eating in the face of adverse consequences characterizes some eating disorders, similar to the way in which compulsive drug intake characterizes drug addiction, it might be considered an addiction in its own right. Moreover, numerous review articles have recently drawn a connection between the neural circuits activated in the seeking/intake of palatable food and drugs of abuse. Based on this observation, food addiction has emerged as an area of intense scientific research, and accumulating evidence suggests that it is possible to model some aspects of food addiction in animals. The development of well-characterized animal models would advance our understanding of the etiologic neural factors involved in eating disorders, such as compulsive overeating, and it would permit to propose targeted pharmacological therapies. However, to date, little evidence has been reported of continued food seeking and intake despite its harmful consequences in rats and mice. © 2013 Springer Science+Business Media, LLC
Interactions between experience, genotype and sex in the development of individual coping strategies
Coping strategies, the first line of defense against adversities, develop through experience. There is consistent evidence that both genotype and sex contribute to the development of dysfunctional coping, leading to maladaptive outcomes of adverse experiences or to adaptive coping that fosters rapid recovery even from severe stress. However, how these factors interact to influence the development of individual coping strategies is just starting to be investigated. In the following review, we will consider evidence that experience, sex, and genotype influence the brain circuits and neurobiological processes involved in coping with adversities and discuss recent results pointing to the specific effects of the interaction between early experiences, genotype, and stress in the development of functional and dysfunctional coping styles