Individual variability in synaptic gene expression and synapse density in induced pluripotent stem cell–derived neurons predicted macro-scale alterations in gray matter volume and gamma-band activity in patients with Schizophrenia.
SIRS2026.
This genetic association study tests whether genetically driven variability in excitatory neurons’ transcriptome and synapse density in patient-derived neurons in vitro explain individual changes in cortical morphology, electrophysiology, and cognitive impairments in vivo.
Why are some people unable to hear from birth, even though their inner ear appears intact? One possible cause lies in the so-called OTOF gene. It plays a central role in transmitting sound signals from the hair cells to the auditory nerve. Without this function, acoustic information does not reach the brain.
Researchers from the German Primate Center—Leibniz Institute for Primate Research, the University Medical Center Göttingen, and the Max Planck Institute for Multidisciplinary Sciences have now, for the first time, generated marmosets in which this gene has been knocked out precisely. The animals are healthy and develop normally, but are deaf from birth. This provides the first primate model that realistically replicates key characteristics of human deafness. The results are published in Nature Communications.
Hearing loss is one of the most common congenital sensory disorders in humans. A major cause is a defect in the OTOF gene. This gene ensures that the protein otoferlin is produced in the inner ear. This protein is necessary for sound signals to travel from the hair cells to the auditory nerve. Without it, the ear still functions externally, but the signals do not reach the brain.
Centenarians often live to 100+ due to a combination of protective genetic factors, which account for up to 50%, and healthy lifestyles, such as plant-forward diets, regular, natural movement and strong social connections. While these “agers” often possess unique immune system signatures, understanding the metabolic signs of healthy aging is not yet fully understood.
In a new study from Boston University Chobanian & Avedisian School of Medicine, researchers have discovered that centenarians have a distinct blood metabolite pattern that is not just an extension of normal aging. In particular, they show uniquely higher levels of certain primary and secondary bile acids and preserved levels of several steroids, patterns that diverge from the typical age trends seen in non-centenarians and that are linked to lower death risk. The study is published in the journal GeroScience.
“Our study points to measurable chemical fingerprints in the blood that are associated with living a very long and healthy life. If we can understand those fingerprints, we may identify biological pathways that could contribute to protecting people from age-related decline,” explains corresponding author Stefano Monti, Ph.D., professor of medicine at the school.
New in eNeuro from Periandri et al: Systematically comparing brain markers affected by brief versus long-term exposure to alcohol in mice unveils shared and different mechanisms that may inform alcohol use disorder treatment development.
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Epigenetic and transcriptional mechanisms are key contributors to alcohol use disorder (AUD). However, a better understanding of the specific genes, transcripts, and chromatin marks affected is necessary to inform novel pharmacotherapies. Here, we systematically investigate the genome-wide epigenetic and transcriptomic effects of ethanol across key brain regions relevant to AUD and assess how these outcomes differ between acute and chronic exposure in male C57BL/6J mice. We show that alcohol-derived acetate contributes to histone acetylation in the brain in response to acute or chronic exposure, with a broader and more robust effect following repeated exposure. Further, we find that chromatin and transcriptomic changes elicited by acute or chronic ethanol exposure are predominantly specific to brain region, and observe more robust dysregulation of gene and transcript expression following acute exposure. We show that ethanol-induced transcriptional changes are paradigm-dependent in some brain regions, most strikingly in the ventral hippocampus. Overall, our results systematically illuminate and compare key epigenetic and transcriptomic outcomes linked to acute and chronic ethanol exposure, which will guide the development of future therapeutic interventions.
Significance Statement This is the first study to systematically investigate epigenetic and transcriptomic changes following acute or chronic exposure to alcohol, focusing on key regions previously linked to substance use disorders. We show the molecular impact of alcohol varies among brain regions and in part depends on the extent of alcohol exposure. Our results provide unprecedented detail on how alcohol affects transcriptional regulation in the brain, which in turn will inform the development of needed novel therapeutic interventions for alcohol use disorder.
Retroperitoneal fibrosis is a rare immune-mediated disease characterised by a periaortoiliac fibro-inflammatory tissue that often encases neighbouring structures (eg, ureters). Idiopathic retroperitoneal fibrosis can be isolated or part of IgG4-related disease, whereas secondary forms recognise different aetiologies, such as histiocytosis, malignancies, and infections. Idiopathic retroperitoneal fibrosis has a multifactorial origin, with genetic, environmental, and lifestyle factors being main contributors.
Scientists have identified molecules that can protect the eye’s cone cells from degeneration, a major cause of vision loss. The discovery points to new drug targets—and even uncovers compounds that may be harmful.
Researchers led by Botond Roska at the Institute of Molecular and Clinical Ophthalmology Basel (IOB), along with an international team, have uncovered genetic pathways and chemical compounds that can help protect cone photoreceptors. These cells are damaged in diseases such as age-related macular degeneration, a leading cause of vision loss.
Why cone cells matter for sight.
From the article:
The study also identified specific brain cell types associated with the genetic patterns.
For the schizophrenia bipolar group, the strongest genetic signals appeared in genes active in excitatory neurons. These neurons transmit signals that activate other brain cells and help different parts of the brain communicate.
In contrast, genetic risk tied to internalizing disorders such as depression, anxiety, and PTSD showed stronger links to oligodendrocytes. These cells help nerve signals travel more efficiently through the brain.
“The findings suggest these ‘support cells’ might play an important role in those conditions,” said Verhulst, research assistant professor and an expert in quantitative and statistical genetics.”
A massive genetic analysis of more than 6 million people is revealing new clues about why mental health disorders frequently overlap.