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Category: neuroscience

Polyamine metabolism as a regulator of cellular and organismal aging

Polyamines — putrescine, spermidine, and spermine — are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.

Role of Dopamine in Pain

Dopamine is a member of a class of molecules called the catecholamines, which serve as neurotransmitters and hormones. In the brain, dopamine serves as a neurotransmitter and is released from nerve cells to send signals to other nerves. Outside of the nervous system, it acts as a local chemical messenger in several parts of the body.

Image Copyright: Meletios, Image ID: 71,648,629 via shutterstock.com

A number of important neurodegenerative diseases are associated with abnormal function of the dopamine system and some of the main medications used to treat those illnesses work by changing the effects of dopamine. The condition Parkinson’s disease is caused by a loss of dopamine secreting cells in a brain area called the substantia nigra.

Grant supports research into how microglia may spread toxic tau in Alzheimer’s

A paper describing Hopp’s upcoming study published on the CureAlz website, titled, “How Do Microglia Contribute to the Spread of Tau Pathology in Alzheimer’s Disease?”, says that while tau aggregates are a defining feature of Alzheimer’s disease and closely track with brain cell loss, memory problems and cognitive decline, much still isn’t known about how it spreads or what role the brain’s immune system plays in the process.

There is evidence, it says, that toxic forms of tau, which have become “misfolded” or dysfunctional, act like a “bad influence.”

“When they encounter nearby healthy tau proteins, they cause them to misfold as well, triggering a chain reaction that spreads from one brain region to another,” according to the paper. “Microglia … are among the first to encounter these toxic tau ‘seeds.’ Normally, microglia protect the brain by clearing debris and helping repair damage. But growing evidence suggests that microglia may also contribute to tau’s spread by engulfing misfolded tau and inadvertently releasing it, thereby amplifying its harmful effects.”

A researcher with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio has received a two-year, $402,500 grant award from the Cure Alzheimer’s Fund to study how microglia, the brain’s resident immune cells, paradoxically might contribute to the spread of toxic forms of tau protein in the disease.

Sarah C. Hopp, PhD, associate professor of pharmacology with the Biggs Institute and the South Texas Alzheimer’s Disease Research Center, along with her lab have been instrumental in uncovering the behavior of microglia. UT Health San Antonio is the academic health center of The University of Texas at San Antonio.

Starting this month, Hopp’s lab will test the hypothesis that microglial uptake of tau is a key mechanism driving its spread through the brain, and that specific molecular pathways determine whether this process protects or harms neurons. The Cure Alzheimer’s Fund, also known as CureAlz, is a nonprofit organization that funds research “with the highest probability of preventing, slowing or reversing Alzheimer’s disease.”

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Key alterations discovered in the cerebral cortex of people with psychosis

Researchers at the University of Seville have analyzed alterations in the cerebral cortex in people suffering from psychosis. Their findings show that psychosis does not follow a single trajectory, but rather its evolution depends on a complex interaction between brain development, symptoms, cognition and treatment. The authors therefore emphasize the need to adopt more personalized approaches that take individual differences into account in order to better understand the disease and optimize long-term therapeutic strategies.

Psychosis is a set of symptoms—such as hallucinations and delusions—that are common in schizophrenia and involve a loss of contact with reality. From their first manifestation, known as the first psychotic episode, these symptoms can appear and evolve in very different ways between individuals, thus making schizophrenia a particularly complex disorder.

The results of the study show that, at the time of the first episode, people with psychosis present a reduction in cortical volume, which is particularly marked in regions with a high density of serotonin and dopamine receptors, key neurotransmitters in both the pathophysiology of psychosis and the mechanism of action of antipsychotics. The data also suggest that both neurons and other brain cells involved in inflammatory and immunological processes may play an important role in the disease.

Leveraging current steering and the biophysics of spike generation for cellular-resolution electrical stimulation of neurons

Vasireddy et al. provide a framework for electrical stimulation current steering using several microelectrodes to most effectively target individual neurons in a population. A biophysically inspired mathematical model fits the linear and nonlinear responses of neurons, and data-driven regression models are used to efficiently find the most selective electrical stimulation patterns.

Electricity creates consciousness

Are we thinking about consciousness in the wrong way?

Nick Lane is an multi-award-winning biochemist and an outstanding science communicator in the origins of life field. He is a Professor of Evolutionary Biochemistry at University College London.

Tap the link to watch his talk now.

How could calcium ions rushing through a membrane generate the taste of coffee, the smell of a rose or the feeling of love? Join celebrated biochemist, Nick Lane, as he argues that the deep logic of life is at root an electrical phenomenon.’His theories are ingenious, breathtaking in scope, and challenging in every sense’ — The Guardian.

A neurobiological perspective on prolonged grief disorder

The neurobiology of why some brains cannot move on from loss.

Prolonged grief disorder (PGD) is a psychiatric condition that describes individuals who experience persistent grief reactions characterized by preoccupation with the loss. This review provides an overview of the evidence on neurobiological processes associated with PGD. We propose that, although the neurobiological circuitry of PGD overlaps with that of anxiety and depression, it also involves neural responses that reflect the distinct symptom profiles of people with PGD. Specifically, while recruitment of cognitive control and salience networks is observed across common mental disorders, there is evidence that aberrant neural processes implicated in reward processes and appetitive functions are somewhat distinctive to PGD.

Similar kinases play distinct roles in the brain—what this could mean for future therapies

Structurally, they look similar: MNK1 and MNK2 belong to the same enzyme family and are best known for regulating how cells make proteins. Their starring role in such a crucial cellular function has cast them into the spotlight as potential drug targets to treat nervous system disorders and chronic pain. But would it matter whether a drug targets only one of them?

In a study published in Molecular Psychiatry, researchers led by Rosalba Olga Proce, a doctoral student in the Molecular and Cellular Basis of Behavior lab led by Dr. Hanna Hornberg at the Max Delbruck Center, set out to determine whether the two enzymes—also called kinases—perform distinct functions in the brain. The team found clear differences. Mice lacking MNK1 showed less interest in newly introduced objects than controls and impaired memory of objects. By contrast, mice without MNK2 appeared normal in object recognition tests but showed enhanced interest in social contacts.

“The behavioral differences we observed suggest that each kinase has a specialized function,” says Proce. “It might be preferable to target each kinase individually when designing drugs.”

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