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Category: neuroscience

Blinding Integrity in Psychedelic Randomized Clinical Trials: A Systematic Review

Functional unblinding was common in most psychedelic randomized clinical trials for psychiatric disorders, with 70% correctly identifying treatment allocation, raising concerns for trial validity.

Question What is the prevalence of blinding integrity assessment and the extent of functional unblinding in psychedelic randomized clinical trials (RCTs) for psychiatric disorders?

Findings Of 112 RCTs identified, 29.5% (n = 33) evaluated blinding integrity. Functional unblinding was substantial: psilocybin, lysergic acid diethylamide (LSD), and ayahuasca studies frequently reported blinding failure values of more than 90% among participants and raters; inert placebo-controlled 3,4-methylenedioxymethamphetamine (MDMA) trials exceeded 85%; ketamine trials rarely assessed blinding (17.9%) but showed improved preservation with midazolam vs saline controls.

Meaning Functional unblinding is pervasive in psychedelic RCTs, underscoring the need for standardized assessment methods and improved trial designs to ensure valid efficacy evaluations.

Songbird connectome reveals tunneling of migratory neurons in the adult striatum

Despite its small size—typically only several inches, beak to tail—the zebra finch is a remarkable learner. A songbird native to Australia, it’s renowned for its ability to pick up new songs.

That talent has made it a favorite of scientists studying how animal brains imprint new skills, particularly vocal learning, or the capacity to perfect new sounds. And now researchers at Boston University have discovered another quirk to the zebra finch brain—one that could also have implications for understanding our own gray matter.

In a study that looked at the bird’s brain in unprecedented detail, they uncovered new insights into a mechanism known as neurogenesis—the birth, migration, and maturation of neurons—that may help the brain learn, add new skills, and restore and repair itself.

Observing the finch brain using a high-powered microscope, the researchers watched as new neurons bullied their way through the brain en route to bolstering existing circuits and connections. They’d expected the neurons to gingerly step around established brain structures, including more mature brain cells, to better preserve them; instead, they saw the neurons tunnel right through, squishing and shoving as they went. That may help the birds learn new things or repair damage, but it could also come with a cost to existing cells and memories.

According to the BU-led team, their findings could help explain why neurogenesis may not occur in humans beyond the womb, increasing our vulnerability to a range of brain disorders. The findings were published in Current Biology.

Abstract: Current Biology

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Continue reading “Songbird connectome reveals tunneling of migratory neurons in the adult striatum” | >

Long-Term Outcomes and Recovery Trajectories in Out-of-Hospital Cardiac Arrest: A 2-Year Follow-Up of the Randomized Clinical TTM2 Trial

Following out-of-hospital cardiac arrest, targeted hypothermia did not affect societal participation or cognitive function at 24 months compared with normothermia; most recovery occurred within 6 months.

Question Does hypothermia after out-of-hospital cardiac arrest affect societal participation or cognitive functioning at 24 months post arrest, and how do these outcomes evolve over time?

Findings This follow-up of the randomized clinical Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest trial found no significant differences in societal participation or cognitive functioning between targeted hypothermia and normothermia at 24 months. Overall recovery was limited beyond 6 months.

Meaning Targeted hypothermia compared with normothermia did not affect outcomes 24 months post arrest, suggesting no longer-term effect of hypothermia for the explored outcomes; 6 months may suffice as an end point when assessing functional or cognitive outcomes after out-of-hospital cardiac arrest.

People who consume ultra-processed foods have worse muscle health, study suggests

Researchers found that a diet high in ultra-processed foods is associated with higher amounts of fat stored inside thigh muscles, regardless of calorie or fat intake, physical activity or sociodemographic factors in a population at risk for knee osteoarthritis. Results of the study were published in Radiology. Higher amounts of intramuscular fat in the thigh could potentially increase the risk for knee osteoarthritis.

Ultra-processed foods usually have longer shelf lives and can be highly appealing and convenient. They contain a combination of sugar, fat, salt and carbohydrates which affect the brain’s reward system, making it hard to stop eating.

These foods include breakfast cereals, margarines/spreads, packaged snacks, hot dogs, soft drinks and energy drinks, candies and desserts, frozen pizzas, ready-to-eat meals, mass-produced packaged breads and buns, which all include synthesized ingredients.

Long-Term Cognitive Ability and Academic Achievement After Childhood Severe Malaria

Among children with a history of CerebralMalaria or severe malarial anemia, long-term follow-up demonstrated lower overall cognitive ability and lower math achievement compared with unaffected children when assessed 4 to 15 years after the index episode of Malaria.

Attention and reading scores did not differ, and outcomes among children with other forms of severe malaria were similar to unaffected children.

These findings indicate that specific severe malaria phenotypes are associated with persistent cognitive and academic effects into later childhood and adolescence, with implications for long-term follow-up and supportive services.

ESCMIDGlobal2026.

This descriptive analysis uses a subset of data from the Malarial Impact on Neurobehavioral Development (MIND) cohort study to assess whether severe malaria in Ugandan children is associated with long-term cognitive impairment or decreased academic achievement.

Epigenetic biomarkers in neurodegenerative diseases: from molecular signatures to therapeutic targets

Epigenetic molecular signatures as biomarkers in neurodegenerative diseases.

Integration of multiomic data is driving the development of cell-type-resolved reference atlases and molecular signatures of neurodegeneration.

Next-generation epigenetic editors are enabling causal interrogation of disease associated marks, revealing disease driving and potentially modifiable epigenetic mechanisms.

Altered chromatin architecture and global epigenomic dysregulation are emerging hallmarks of neurodegenerative diseases, detectable not only in the brain but also in peripheral biofluids.

Peripheral chromatin accessibility and conformation signatures are emerging as clinically actionable biomarkers for early diagnosis, prognosis, and stratification.

Circulating DNA (hydroxy-)methylation profiles offer new avenues for noninvasive biomarker discovery for neurodegenerative diseases, but low yield and sensitivity in detecting neuronal signals remain key challenges. sciencenewshighlights ScienceMission https://sciencemission.com/Epigenetic-biomarkers-in-ND

Continue reading “Epigenetic biomarkers in neurodegenerative diseases: from molecular signatures to therapeutic targets” | >

Novel Opioid Offers Potent Pain Relief Without Classic Side Effects

Researchers have discovered a novel synthetic opioid that provided potent pain relief in preclinical models without many of the dangerous side effects that limit current opioid therapies.

The compound, N-desethyl-fluornitrazene (DFNZ), produced strong analgesia in rodents without causing respiratory depression, tolerance, or other indicators of potential addiction, reported the researchers, led by Michael Michaelides, PhD, with the National Institute on Drug Abuse (NIDA).

“Opioid pain medications are essential for medical purposes, but can lead to addiction and overdose. Developing a highly effective pain medication without these drawbacks would have enormous public health benefits,” NIDA Director Nora D. Volkow, MD, said in a news release.

A novel mu-opioid receptor agonist showed strong analgesia without respiratory depression, tolerance, or significant addiction signals in animal models.

Waves of gene control reveal how a key gene times limb development

In a new study published in Genes & Development, research led by Dr. Lila Allou at the MRC Laboratory of Medical Sciences (LMS) in London and Professor Stefan Mundlos at the Max Planck Institute for Molecular Genetics and Charité in Berlin demonstrates how different regulatory genetic elements coordinate the temporal activity of a key developmental gene. Their findings likely explain subtle differences seen in patients with congenital limb malformations, for which the underlying disease mechanisms often remain unknown.

Although every cell contains the same genes, not all genes are active at any given time. Gene regulation is a fundamental process that ensures only the necessary genes are expressed in each cell type. This is why, for example, neurons differ in structure and function from muscle cells. Precise fine-tuning of gene regulation is especially critical during development. Timed waves of transcriptional activity ensure that an embryo develops into a healthy organism with properly positioned and formed limbs, organs, and tissues. This process is driven by specialized genes and controlled by regulatory elements in the genome.

Attenuated Single Neuron and Network Hyperexcitability Following MicroRNA-134 Inhibition in Mice with Drug-Resistant Temporal Lobe Epilepsy

JNeurosci: Findings from Quintana-Sarti et al. help explain how targeting microRNA-134 in mice can reduce seizure activity and support the continued development of this novel RNA-based approach for the treatment of epilepsy.

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The multifactorial pathophysiology of acquired epilepsies lends itself to a multitargeting therapeutic approach. MicroRNAs (miRNA) are short noncoding RNAs that individually can negatively regulate dozens of protein-coding transcripts. Previously, we reported that central injection of antisense oligonucleotides targeting microRNA-134 (Ant-134) shortly after status epilepticus potently suppressed the development of recurrent spontaneous seizures in rodent models of temporal lobe epilepsy. The mechanism(s) of these antiseizure effects remain, however, incompletely understood. Here we show that intracerebroventricular microinjection of Ant-134 in male mice with preexisting epilepsy caused by intra-amygdala kainic acid-induced status epilepticus potently reduces the occurrence of spontaneous seizures.

Oxidative Stress and Neuroinflammation in Parkinson’s Disease: The Role of Dopamine Oxidation Products

Parkinson’s disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It is characterized by the preferential degeneration of nigrostriatal dopaminergic neurons, which is responsible for the motor symptoms of PD patients. The pathogenesis of this multifactorial disorder is still elusive, hampering the discovery of therapeutic strategies able to suppress the disease’s progression. While redox alterations, mitochondrial dysfunctions, and neuroinflammation are clearly involved in PD pathology, how these processes lead to the preferential degeneration of dopaminergic neurons is still an unanswered question. In this context, the presence of dopamine itself within this neuronal population could represent a crucial determinant.

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