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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A Systematic Review of Genetic Polymorphisms Associated with Binge Eating Disorder

The genetic polymorphisms involved in the physiopathology of binge eating disorder (BED) are currently unclear. This systematic review aims to highlight and summarize the research on polymorphisms that is conducted in the BED. We looked for observational studies where there was a genetic comparison between adults with BED, in some cases also with obesity or overweight, and healthy controls or obesity/overweight without BED. Our protocol was written using PRISMA. It is registered at PROSPERO (identification: CRD42020198645). To identify potentially relevant documents, the following bibliographic databases were searched without a time limit, but until September 2020: PubMed, PsycINFO, Scopus, and Web of Science. In total, 21 articles were included in the qualitative analysis of the systematic review, as they met the eligibility criteria. Within the selected studies, 41 polymorphisms of 17 genes were assessed. Overall, this systematic review provides a list of potentially useful genetic polymorphisms involved in BED: 5-HTTLPR (5-HTT), Taq1A (ANKK1/DRD2), A118G (OPRM1), C957T (DRD2), rs2283265 (DRD2), Val158Met (COMT), rs6198 (GR), Val103Ile (MC4R), Ile251Leu (MC4R), rs6265 (BNDF), and Leu72Met (GHRL). It is important to emphasize that Taq1A is the polymorphism that showed, in two different research groups, the most significant association with BED. The remaining polymorphisms need further evidence to be confirmed

Positive emotional arousal increases duration of memory traces: different role of dopamine D1 receptor and β-adrenoceptor activation.

We investigated the effects of post-training administration of dopamine D1 receptor antagonist SCH 23390 and beta-adrenergic receptor antagonist Propranolol on memory retention of an object sampled in a state of positive emotional arousal. Saline-treated mice trained and tested under high emotional/motivational arousal (High) showed discrimination of a novel object both 24 and 96 h post-training. Instead, mice trained and tested under low motivational arousal (Low) were unable to discriminate the novel object 96 h post-training. Both a high (2 mg/kg) and a low (1 mg/kg) dose of Propranolol reduced object discrimination in High mice tested 24 h post-training, whereas neither dose was effective in Low mice. A high dose of SCH 23390 (0.025 mg/kg) reduced discrimination of the novel object in High mice tested both 24 and 96 h post-training, whereas a low dose of the D1 antagonist (0.01 mg/kg) reduced discrimination in High mice tested 96 h post-training and abolished discrimination in Low mice tested 24 h after training. (C) 2014 Elsevier Inc. All rights reserved.We investigated the effects of post-training administration of dopamine D1 receptor antagonist SCH 23390 and β-adrenergic receptor antagonist Propranolol on memory retention of an object sampled in a state of positive emotional arousal. Saline-treated mice trained and tested under high emotional/motivational arousal (High) showed discrimination of a novel object both 24 and 96h post-training. Instead, mice trained and tested under low motivational arousal (Low) were unable to discriminate the novel object 96h post-training. Both a high (2mg/kg) and a low (1mg/kg) dose of Propranolol reduced object discrimination in High mice tested 24h post-training, whereas neither dose was effective in Low mice. A high dose of SCH 23390 (0.025mg/kg) reduced discrimination of the novel object in High mice tested both 24 and 96h post-training, whereas a low dose of the D1 antagonist (0.01mg/kg) reduced discrimination in High mice tested 96h post-training and abolished discrimination in Low mice teste

Dendritic spine density and EphrinB2 levels of hippocampal and anterior cingulate cortex neurons increase sequentially during formation of recent and remote fear memory in the mouse

Memory consolidation is a dynamic process that involves a sequential remodeling of hippocampal–cortical circuits. Although synaptic events underlying memory consolidation are well assessed, fine molecular events controlling this process deserve further characterization. To this aim, we challenged male C57BL/6N mice in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7 days or 36 days later. Mice displayed a strong fear response at all time points with an increase in dendritic spine density and protein levels of the cell adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post conditioning (p.c.), and in anterior cingulate cortex (ACC) neurons 36 days p.c. We then investigated whether the formation of remote memory and neuronal modifications in the ACC would de- pend on p.c. protein synthesis in hippocampal neurons. Bilateral intrahippocampal infusions with the protein synthesis inhibitor anisomycin administered immediately p.c. decreased fear response, neuronal spine growth and EphrinB2 protein levels of hippocampal and ACC neurons 24 h and 36 days p.c., respectively. Anisomycin infusion 24 h p.c. had no effects on fear response, increase in spine density and in EphrinB2 protein levels in ACC neurons 36 days p.c. Our results thus confirm that early but not late p.c. hippocampal protein synthesis is necessary for the formation of remote memory and provide the first evidence of a possible involvement of EphrinB2 in neuronal plasticity in the AC

Role of prefrontal 5-HT in the strain-dependent variation in sign-tracking behavior of C57BL/6 and DBA/2 mice

Rationale The expression of sign-tracking (ST) phenotype over goal-tracking (GT) phenotype has been associated to different aspects of impulsive behavior, and depletions of brain serotonin (5-HT) have been shown to selectively increase impulsive action as well as ST. Objectives The present study aimed at testing the relationship between reduced brain 5-HTavailability and expression of ST phenotype in a genetic model of individual variation in brain 5-HT functionality. Inbred DBA/2J (DBA) mice are homozygous for the allelic variant of the TPH-2 gene causing lower brain 5-HT function in comparison with C57BL/6J (C57) inbred mice. Materials Young adult (10 weeks) and adult (14 weeks) C57 and DBA mice were trained in a Pavlovian conditioned approach (PCA) paradigm. Lever-directed (ST) and magazinedirected (GT) responses were measured in 12 daily conditioning sessions. In a second experiment, effect of the medial prefrontal cortex (mPFC) 5-HT depletion by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) was assessed on acquisition of ST phenotype in adult C57 mice, according to their higher 5-HT functionality compared to DBA mice. Results Young adult mice of both strains developed ST phenotype, but only adult DBA mice developed ST phenotype. 5-HT depletion in the mPFC of adult C57 mice completely changed their phenotype, as shown by their increased ST. Conclusions These findings indicate that ST phenotype can be the expression of a transitory late developmental stage and that genetic factors determine persistence of this phenotype in adulthood. These findings also support a role of 5-HT transmission in PFC in constraining development of ST phenotyp

The Emotional Personality of Psychotherapists: A Pilot Research with Gestalt-Therapy Clinicians

Since the discovery of “countertransference”, it was recognized that the therapist’s personality plays an important role in determining the course of psychotherapy. However, systematic empirical works on this topic have been sparse compared to the enormous amount of theoretical literature. Therefore, in the following pilot study, the emotional profile of psychotherapists was investigated using the Affective Neuroscience Personality Scales (ANPS), a quantitative measure of the basic emotional foundations of human personality based on Jaak Panksepp’s neuro-ethological studies. More specifically, we submitted the ANPS to a population of Gestalt-therapists to ascertain if they share a characteristic emotional profile (1) and if the emotional traits of personality are related to specific intersubjective competences (2). Our results show that, compared with normal population, the personality of therapists is characterized by higher expression of PLAYFULNESS/joy, CARE/nurturance and Spirituality, as well as a significant decrease in the expression of the RAGE/anger disposition. Such emotional traits, that are not influenced by the experience of training, correlate with important relational skills such as empathy, reflective functioning and interoceptive awareness. Therefore, unlearned emotional dispositions have high relevance in the development of the therapist’s sensitivity to the phenomenological intersubjective field, a competence recently called “Aesthetic Relational Knowledge” in a contemporary Gestalt-approach. Our findings may have implications for training therapists and optimizing treatment outcomes

Sensitivity to cocaine in adult mice is due to interplay between genetic makeup, early environment and later experience

Although early aversive postnatal events are known to increase the risk to develop psychiatric disorders later in life, rarely they determine alone the nature and outcome of the psychopathology, indicating that interaction with genetic factors is crucial for expression of psychopathologies in adulthood. Moreover, it has been suggested that early life experiences could have negative consequences or confer adaptive value in different individuals. Here we suggest that resilience or vulnerability to adult cocaine sensitivity depends on a “triple interaction” between genetic makeup x early environment x later experience. We have recently showed that Repeated Cross Fostering (RCF; RCF pups were fostered by four adoptive mothers from postnatal day 1 to postnatal day 4. Pups were left with the last adoptive mother until weaning) experienced by pups affected the response to a negative experience in adulthood in opposite direction in two genotypes leading DBA2/J, but not C57BL/6J mice, toward an “anhedonia-like” phenotype. Here we investigate whether exposure to a rewarding stimulus, instead of a negative one, in adulthood induces an opposite behavioral outcome. To test this hypothesis, we investigated the long-lasting effects of RCF on cocaine sensitivity in C57 and DBA female mice by evaluating conditioned place preference induced by different cocaine doses and catecholamine prefrontal-accumbal response to cocaine using a “dual probe” in vivo microdialysis procedure. Moreover, cocaine-induced c-Fos activity was assessed in different brain regions involved in processing of rewarding stimuli. Finally, cocaine-induced spine changes were evaluated in the prefrontal-accumbal system. RCF experience strongly affected the behavioral, neurochemical and morphological responses to cocaine in adulthood in opposite direction in the two genotypes increasing and reducing, respectively, the sensitivity to cocaine in C57 and DBA mice

Unstable maternal environment affects stress response in adult mice in a genotype-dependent manner

Early postnatal events exert powerful effects on development, inducing persistent functional alterations in different brain network, such as the catecholamine prefrontal-accumbal system, and increasing the risk of developing psychiatric disorders later in life. However, a vast body of literature shows that the interaction between genetic factors and early environmental conditions is crucial for expression of psychopathologies in adulthood. We evaluated the long-lasting effects of a repeated cross-fostering (RCF) procedure in 2 inbred strains of mice (C57BL/6J, DBA/2), known to show a different susceptibility to the development and expression of stress-induced psychopathologies. Coping behavior (forced swimming test) and preference for a natural reinforcing stimulus (saccharine preference test) were assessed in adult female mice of both genotypes. Moreover, c-Fos stress-induced activity was assessed in different brain regions involved in stress response. In addition, we evaluated the enduring effects of RCF on catecholamine prefrontal-accumbal response to acute stress (restraint) using, for the first time, a new "dual probes" in vivo microdialysis procedure in mouse. RCF experience affects behavioral and neurochemical responses to acute stress in adulthood in opposite direction in the 2 genotypes, leading DBA mice toward an "anhedonic-like" phenotype and C57 mice toward an increased sensitivity for a natural reinforcing stimulus

MicroRNA-34a regulates the depression-like behavior in mice by modulating the expression of target genes in the Dorsal Raphè

Chronic or cumulative stress sustained over a long period of time increases the risk of affective illness. Mounting clinical and preclinical evidences support the involvement of the miR-34 family of microRNAs in stress-related psychiatric conditions and in the neurobiological mechanisms that underlie the regulation of stress response. In this study, by molecular and behavioral approaches, we investigate the role of miR-34 in the behavioral and functional modifications induced in the mouse brain by a chronic stress exposure (repeated restraint) and try to elucidate the underlying mechanism by the identification of miR-34 “in vivo” multiple downstream targets, under the context of a stressful challenge. We show that the miR-34a, under chronic stress, is highly induced in the mouse Dorsal Raphe Nuclei, where its recruitment is necessary to produce the behavioral modifications and impact the serotonergic system functionality. Moreover, through next generation RNA-seq in Ago-2 -bound mRNAs (RISC-Seq), we identified genes that are targeted by miR-34 in response to the chronic stress, and that are likely to mediate its effect

Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia.

Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE