Neuroscience Applied最新文献

The bond between a mother and her infant is one of the strongest social bonds found in mammals. Consequently, the loss of an infant has immense psychological and physiological effects on the caregiver. Despite the significance of this bereavement, only a few studies have investigated the neurobiological impact of offspring loss in mothers. In an approach to fill this gap, we studied the effects of losing all pups the day after giving birth on rat mothers' brain and stress-coping behavior. Specifically, dams experienced 1-, 3-, or 6-days of total offspring loss. We analyzed the neuronal activity and oxytocin receptor (OXT-R) binding in the brain limbic and maternal network regions, as well as the stress response and stress-coping strategies. Following 1 day of loss, the mothers' neuronal activity increased in the limbic system resulting in a positive correlation between the prelimbic cortex and basolateral amygdala, while OXT-R binding was decreased in the central amygdala following up to 3 days of loss. At all three timepoints, plasma corticosterone concentrations did not differ either under basal conditions or following stressor exposure. Remarkably, following 6 days of offspring loss, the mothers showed a significant increase in passive stress-coping behavior, marking the first evidence of offspring loss affecting rat mothers' stress-coping behavior. Our results emphasize the significant impact of offspring loss on the mothers’ neuronal activity and brain oxytocin system thereby providing novel insight into the short-term neurobiological traces of grief and paving new avenues for future research in this field.

Semaglutide, a glucagon-like peptide-1 receptor agonist, is an effective drug reducing body weight and decreasing motivation for palatable food. The mechanisms underlying its effects on food reward remain unclear. We aimed to determine the impact of semaglutide on food reward collection and dopamine-neuron activity in the ventral tegmental area (VTA) upon exposure to a cue-induced sucrose delivery task.

Pitx3-cre mice were injected with cre-dependent GCaMP6s virus into the VTA, to measure the activity of dopaminergic neurons in the VTA using in vivo fiber photometry. Mice were trained on a Pavlovian sucrose conditioning paradigm in which a 5-s cue signaled a 20% sucrose reward. Upon stable performance, semaglutide or vehicle was intraperitoneally injected during the task.

1 mg/kg semaglutide reduced the number of collected rewards and licks during the task. Semaglutide increased VTA dopamine neuron activity during sucrose collection but not during the cue. Lower doses of semaglutide (0.1 and 0.3 mg/kg) reduced chow intake but not sucrose intake nor VTA dopamine activity in the task.

Semaglutide reduces appetite but increases VTA dopamine signaling during reward collection. Semaglutide does not influence dopamine signaling during the presentation of food cues.

The ability to flexibly adapt thoughts and behaviours represents a fundamental attribute for behavioural success. Impairments in aspects of cognitive flexibility are found as transdiagnostic latent phenotypes of obsessive-compulsive symptomatology and are present within a range of mental disorders and within the population at large. In this narrative review, we focus on the attentional set-shifting aspect of cognitive inflexibility, which has been largely investigated in the context of obsessive-compulsive spectrum disorders and is thought to underpin perseverative symptomatology. We appraise the published literature relating to the putative neurobiological mechanisms, methods of assessment, interventional approaches, and health and wellbeing impacts. We discuss critical knowledge gaps, promising new research avenues, and potential interventional approaches from a clinical and public health perspective. We conclude that cognitive inflexibility has relevance for clinicians in terms of understanding clinical outcomes and tailoring personalised forms of treatments, and for public health professionals in terms of understanding rigid attitudes and adjustment in the current post-pandemic environment.

Mental health problems are highly prevalent worldwide. Stress can precipitate both the onset and recurrence of mental health problems. While many individuals are exposed to similar stressors, there is a large heterogeneity in sensitivity to stress and the extent to which someone subsequently develops mental health issues. A key factor that contributes to an individual's capacity to cope with adversity, referred to as resilience, is genetic variation. Here, we systematically reviewed the effects of genetic variation in the genes encoding the norepinephrine (NE) transporter and receptors on resilience- and mental health-related features in a transdiagnostic approach (i.e., without restrictions regarding factors such as diagnosis or age). Our search yielded 49 studies for inclusion. The current evidence highlights that 1) genetic variations in the NE system (particularly in the ADRA2A and ADRA2B genes) exert influence on some cognitive processes, especially attention and emotional memory; 2) genetic variants in the alpha-2a receptor might play a role in some personality traits; 3) deletion in the ADRA2B and ADRA2C genes seems to be related with altered activity of the amygdala during emotional memory tasks; 4) the link between NE variants and response to methylphenidate are inconclusive. Altogether, these studies provide evidence for a genetic effect of the noradrenergic system in specific resilience- and mental health-related individual characteristics. However, the number of available studies specifically investigating noradrenergic genes were limited, emphasizing the need to perform more research on the noradrenergic system, while taking into account factors such as age, sex, environment, and the potential interactions with other genes.

The canonical Wnt signaling pathway plays a vital role in the developmental processes of the Central Nervous System throughout both prenatal and postnatal stages, as well as in maintaining homeostasis during adulthood. Its complex intracellular cascade involves the participation of key proteins (i.e., GSK3β and β-catenin) to activate the transcription of Wnt target genes. These genes subsequently control processes like cell proliferation, maturation, and the determination of cell fate. Previous studies suggest that this pathway can also be associated with Attention-Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental disorder with multifactorial etiology. This study aimed to clarify if and at what developmental stage the Wnt pathway is altered in ADHD. Accordingly, we carried out proteomic and functional assessments of the Wnt pathway using Western Blot and reporter assays, respectively. These assessments were performed at the induced pluripotent stem cell (iPSC), neural stem cell (NSC), and neuronal phases. IPSCs were generated from somatic cells retrieved from 5 controls and 5 patients diagnosed with ADHD. As opposed to the developmental stage of iPSCs, ADHD NSCs showed alterations in the protein expression of both GSK3β and β-catenin, suggesting increased Wnt activity in the ADHD group. Moreover, Wnt reporter assays confirmed higher Wnt activity in ADHD NSCs. Our molecular findings in NSCs correlated with genetic predisposition to ADHD and clinical traits displayed by their respective donors. In conclusion, these results suggest that a crucial cellular pathway is disrupted in patient-specific NSCs, potentially explaining the developmental deficits clinically exhibited by ADHD patients.

In addition to the general impact of the COVID-19 pandemic on anxiety-related mental state, anxiety and anxiety disorders have also been implicated within ‘post-COVID-19 syndrome’, i.e. following a SARS-CoV-2 infection. The present narrative review provides an update on the current state of knowledge on anxiety and anxiety disorders in the context of post-COVID-19 syndrome, on epidemiological, psychological, and biological factors that may contribute to anxiety following a SARS-CoV-2 infection, as well as on therapy options available for anxiety in the context of post-COVID-19 syndrome. A multi-step systematic literature search of PubMed and Web of Science databases was performed applying the following broad search terms: (“anxiety” OR “anxiety disorder”) AND (“COVID” OR “COVID-19” OR “corona” OR “pandemic” OR “Post-COVID” OR “Long-COVID”). Eligible articles published until November 15, 2022 were included. Meta-analyses identified anxiety prevalence rates ranging from 16.6% to 29.6% after a SARS-CoV-2 infection. Premorbid anxiety has not reliably been shown to be associated with post-COVID-19 syndrome. Female sex, older age, severity of COVID-19 infection, hospitalization, reduced mobility, uncertainty, loneliness and low social support, anxiety sensitivity and cognitive inflexibility as well as biological factors such as immune dysregulation, alterations in the angiotensin system and hypothalamus-pituitary-adrenal axis activation have been identified as potential anxiety risk factors in the context of post-COVID-19 syndrome. Treatment options comprise pharmacotherapy with selective serotonin/noradrenaline reuptake inhibitors and (internet-/computer-based) cognitive behavioral psychotherapy, possibly augmented by mindfulness-based techniques, physical exercise and non-invasive brain stimulation. Provided corroboration of the currently suggested increased risk of anxiety in the context of post-COVID-19 syndrome by future large-scale, prospective studies, a standardized screening for anxiety in patients with a SARS-CoV-2 infection – particularly in individuals with risk factors – and a psychiatric consultation and liaison service should be established to provide preventive and therapeutic interventions as early as possible.