Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress.

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

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Selective attention depends on goal-directed and stimulus-driven modulatory factors, each relayed by different brain rhythms. Under certain circumstances, stress-related states can change the balance between goal-directed and stimulus-driven factors. However, the neuronal mechanisms underlying these changes remain unclear. In this study, we explored how psychosocial stress can modulate brain rhythms during an attentional task and a task-free period. We recorded the EEG and ECG activity of 42 healthy participants subjected to either the Trier Social Stress Test (TSST), a controlled procedure to induce stress, or a comparable control protocol (same physical and cognitive effort but without the stress component), flanked by an attentional task, a 90 s of task-free period and a state of anxiety questionnaire. We observed that psychosocial stress induced an increase in heart rate (HR), self-reported anxiety, and alpha power synchronization. Also, psychosocial stress evoked a relative beta power increase during correct trials of the attentional task, which correlates positively with anxiety and heart rate increase, and inversely with attentional accuracy. These results suggest that psychosocial stress affects performance by redirecting attentional resources toward internal threat-related thoughts. An increment of endogenous top-down modulation reflected an increased beta-band activity that may serve as a compensatory mechanism to redirect attentional resources toward the ongoing task. The data obtained here may contribute to designing new ways of clinical management of the human stress response in the future and could help to minimize the damaging effects of persistent stressful experiences.

Visual sensory processing of external events decreases when attention is internally oriented toward self-generated thoughts and also differences in attenuation have been shown depending on the thought’s modality (visual or auditory thought). The present study aims to assess whether such modulations occurs also in auditory modality. In order to investigate auditory sensory modulations, we compared a passive listening condition with two conditions in which attention was internally oriented as a part of a task; a visual imagery condition and an inner speech condition. EEG signal was recorded from 20 participants while they were exposed to auditory probes during these three conditions. ERP results showed no differences in N1 auditory response comparing the three conditions reflecting maintenance of evoked electrophysiological reactivity for auditory modality. Nonetheless, time-frequency analyses showed that gamma and theta power in frontal regions was higher for passive listening than for internal attentional conditions. Specifically, the reduced amplitude in early gamma and theta band during both inward attention conditions may reflect reduced conscious attention of the current auditory stimulation. Finally, different pattern of beta band activity was observed only during visual imagery which can reflect cross-modal integration between visual and auditory modalities and it can distinguish this form of mental imagery from the inner speech. Taken together, these results showed that attentional suppression mechanisms in auditory modality are different from visual modality during mental imagery processes. Our results about oscillatory activity also confirm the important role of gamma oscillations in auditory processing and the differential neural dynamics underlying the visual and auditory/verbal imagery.

The human gut microbiome is the ecosystem of microorganisms that live in the human digestive system. Several studies have related gut microbiome variants to metabolic, immune and nervous system disorders. Fragile X syndrome (FXS) is a neurodevelopmental disorder considered the most common cause of inherited intellectual disability and the leading monogenetic cause of autism. The role of the gut microbiome in FXS remains largely unexplored. Here, we report the results of a gut microbiome analysis using a FXS mouse model and 16S ribosomal RNA gene sequencing. We identified alterations in the fmr1 KO2 gut microbiome associated with different bacterial species, including those in the genera Akkermansia, Sutterella, Allobaculum, Bifidobacterium, Odoribacter, Turicibacter, Flexispira, Bacteroides, and Oscillospira. Several gut bacterial metabolic pathways were significantly altered in fmr1 KO2 mice, including menaquinone degradation, catechol degradation, vitamin B6 biosynthesis, fatty acid biosynthesis, and nucleotide metabolism. Several of these metabolic pathways, including catechol degradation, nucleotide metabolism and fatty acid biosynthesis, were previously reported to be altered in children and adults with autism. The present study reports a potential association of the gut microbiome with FXS, thereby opening new possibilities for exploring reliable treatments and non-invasive biomarkers.

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Specific city features such as environmental noise have been related to psychological distress. The effects of noise — as a health risk variable — might depend on socioeconomic and demographic factors. However, this has not been fully tested yet. The present work explored the relationship between pedestrians’ first-person experience in the presence of natural urban environmental noise while walking through neighbourhoods in Santiago, Chile. Participants completed a predetermined guided walk. Geo-referenced mobile eye-tracking measured first-person audio-visual perceptual experience while being interviewed in situ. Results show the likelihood of reporting negative experiences is higher when environmental noise increases, while the likelihood of reporting positive experiences is reduced when environmental noise decreases. However, when socioeconomic status is considered as regressor, lower-income neighbourhoods report the inverse effect. We interpret these findings taking into account accessibility to green areas, public safety and access to public facilities that noisy environments afford. We hypothesize that the augmentation of environmental noise in lower-income neighbourhoods is associated with urbanicity benefits. Our results document the phenomenological impact of inequality in urban planning and development.