In utero and post-natal opioid exposure followed by mild traumatic brain injury contributes to cortical neuroinflammation, mitochondrial dysfunction, and behavioral deficits in juvenile rats.

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury (mTBI). Using a rat model of in utero and post-natal oxycodone (IUO) exposure and a low force weight drop model of mTBI, we show that not only neonatal opioid exposure significantly affects neuroinflammation, brain metabolites, synaptic proteome, mitochondrial function, and altered behavior in juvenile rats, but also, in conjunction with mTBI these aberrations are further exacerbated. Specifically, we observed long term metabolic dysregulation, neuroinflammation, alterations in synaptic mitochondria, and impaired behavior were impacted severely by mTBI. Our research highlights the specific vulnerability caused by IUO exposure to a secondary stressor such as later life brain injury. In summary, we present a comprehensive study to highlight the damaging effects of prenatal opioid abuse in conjunction with mild brain injury on the developing brain.

Role of microRNAs in the pathophysiology of addiction.

Addiction is a chronic and relapsing brain disorder characterized by compulsive seeking despite adverse consequences. There are both heritable and epigenetic mechanisms underlying drug addiction. Emerging evidence suggests that non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs, and circular RNAs regulate synaptic plasticity and related behaviors caused by substances of abuse. These ncRNAs modify gene expression and may contribute to the behavioral phenotypes of addiction. Among the ncRNAs, the most widely researched and impactful are miRNAs. The goal in this systematic review is to provide a detailed account of recent research involving the role of miRNAs in addiction. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease.

Filamentation Involves Two Overlapping, but Distinct, Programs of Filamentation in the Pathogenic Fungus Candida albicans.

The ability of the human pathogenic fungus Candida albicans to switch between yeast-like and filamentous forms of growth has long been linked to pathogenesis. Numerous environmental conditions, including growth at high temperatures, nutrient limitation, and exposure to serum, can trigger this morphological switch and are frequently used in in vitro models to identify genes with roles in filamentation. Previous work has suggested that differences exist between the various in vitro models both in the genetic requirements for filamentation and transcriptional responses to distinct filamentation-inducing media, but these differences had not been analyzed in detail. We compared 10 in vitro models for filamentation and found broad genetic and transcriptomic differences between model systems. The comparative analysis enabled the discovery of novel media-independent genetic requirements for filamentation as well as a core filamentation transcriptional profile. Our data also suggest that the physical environment drives distinct programs of filamentation in C. albicans, which has significant implications for filamentation in vivo.