C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides.NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.
<b><i>Background:</i></b> Despite decades of research, little clarity exists regarding pathogenic mechanisms related to schizophrenia. Investigations on the disease biology of schizophrenia have primarily focused on neuronal alterations. However, there is substantial evidence pointing to a significant role for the brain’s microvasculature in mediating neuroinflammation in schizophrenia. <b><i>Summary:</i></b> Brain microvascular endothelial cells (BMEC) are a central element of the microvasculature that forms the blood-brain barrier (BBB) and shields the brain against toxins and immune cells via paracellular, transcellular, transporter, and extracellular matrix proteins. While evidence for BBB dysfunction exists in brain disorders, including schizophrenia, it is not known if BMEC themselves are functionally compromised and lead to BBB dysfunction. <b><i>Key Messages:</i></b> Genome-wide association studies, postmortem investigations, and gene expression analyses have provided some insights into the role of the BBB in schizophrenia pathophysiology. However, there is a significant gap in our understanding of the role that BMEC play in BBB dysfunction. Recent advances differentiating human BMEC from induced pluripotent stem cells (iPSC) provide new avenues to examine the role of BMEC in BBB dysfunction in schizophrenia.
Background Youth with existing psychiatric illness are more apt to use the internet as a coping skill. Because many “in-person” coping skills were not easily accessible during the COVID-19 pandemic, youth in outpatient mental health treatment may have been particularly vulnerable to the development of problematic internet use (PIU). The identification of a pandemic-associated worsening of PIU in this population is critical in order to guide clinical care; if these youth have become dependent upon the internet to regulate their negative emotions, PIU must be addressed as part of mental health treatment. However, many existing studies of youth digital media use in the pandemic do not include youth in psychiatric treatment or are reliant upon cross-sectional methodology and self-report measures of digital media use. Objective This is a retrospective cohort study that used data collected from an app-based ecological momentary assessment protocol to examine potential pandemic-associated changes in digital media youth in outpatient mental health treatment. Secondary analyses assessed for differences in digital media use dependent upon personal and familial COVID-19 exposure and familial hospitalization, as well as factors associated with PIU in this population. Methods The participants were aged 12-23 years and were receiving mental health treatment in an outpatient community hospital setting. All participants completed a 6-week daily ecological momentary assessment protocol on their personal smartphones. Questions were asked about depression (PHQ-8 [8-item Patient Health Questionnaire]), anxiety (GAD-7 [7-item General Anxiety Disorder]), PIU (PIU-SF-6 [Problematic Internet Use Short Form 6]), digital media use based on Apple’s daily screen time reports, and personal and familial COVID-19 exposure. The analyses compared screen time, psychiatric symptoms, and PIU between cohorts, as well as between youth with personal or familial COVID-19 exposures and those without. The analyses also assessed for demographic and psychiatric factors associated with clinically significant PIU-SF-6 scores. Results A total of 69 participants completed the study. The participants recruited during the pandemic were significantly more likely to meet the criteria for PIU based on their average PIU-SF-6 score (P=.02) and to spend more time using social media each day (P=.049). The overall amount of daily screen time did not differ between cohorts. Secondary analyses revealed a significant increase in average daily screen time among subjects who were exposed to COVID-19 (P=.01). Youth with clinically significant PIU-SF-6 scores were younger and more likely to have higher PHQ-8 (P=.003) and GAD-7 (P=.003) scores. No differences in scale scores or media use were found between subjects based on familial COVID-19 exposure or hospitalization. Conclusions Our findings support our hypothesis that PIU may have worsened for youth in mental health treatment during the pandemic, particularly the problematic use of social media. Mental health clinicians should incorporate screening for PIU into routine clinical care in order to prevent potential familial conflict and subsequent psychiatric crises that might stem from unrecognized PIU.
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