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Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles.

SIGNIFICANCE STATEMENT Early-life stress enhances sensitivity to stress later in life, yet the mechanisms of such stress sensitization are largely unknown. Here, we show that neuronal ensembles in corticolimbic brain regions remain hypersensitive to stress across the life span, and quieting these ensembles during experience of adult stress rescues stress hypersensitivity.

Once we fully we understand intelligence it could be essentially increased to nearly infinite levels once everything is quantified like this article talks about 😗😁.

Modern humans have a gene mutation that boosts the growth of neurons in the brain neocortex, a brain region associated with higher intelligence.

By Michael Le Page

Continue reading “A single gene mutation may have made us smarter than Neanderthals” »

Mothers who eat apples and herbs in early pregnancy could be protecting the brain health of their children and grandchildren, a Monash University study using genetic models has found.

The discovery is part of a project that found a mother’s diet can affect not just her child’s brain but also those of her grandchildren.

Published in Nature CellBiology, the Monash Biomedicine Discovery Institute study found that certain foods could help protect against the deterioration of brain function.

Continue reading “A mother’s diet can protect her grandchildren’s brains: genetic model study” »

A protein involved in wound healing can improve learning and memory in ageing mice1.

Platelet factor 4 (PF4) has long been known for its role in promoting blood clotting and sealing broken blood vessels. Now, researchers are wondering whether this signalling molecule could be used to treat age-related cognitive disorders such as Alzheimer’s disease.

“The therapeutic possibilities are very exciting,” says geneticist and anti-ageing scientist David Sinclair at Harvard University in Boston, Massachusetts, who was not involved in the research. The study was published on 16 August in Nature.

Continue reading “Older mouse brains rejuvenated by protein found in young blood” »

This is a significant development that brings hope to the one billion individuals with obesity worldwide. Researchers led by Director C. Justin LEE from the Center for Cognition and Sociality (CCS) within the Institute for Basic Science (IBS) have discovered new insights into the regulation of fat metabolism. The focus of their study lies within the star-shaped non-neuronal cells in the brain, known as ‘astrocytes’. Furthermore, the group announced successful animal experiments using the newly developed drug ‘KDS2010’, which allowed the mice to successfully achieve weight loss without resorting to dietary restrictions.

The complex balance between food intake and energy expenditure is overseen by the hypothalamus in the brain. While it has been known that the neurons in the lateral hypothalamus are connected to fat tissue and are involved in fat metabolism, their exact role in fat metabolism regulation has remained a mystery. The researchers discovered a cluster of neurons in the hypothalamus that specifically express the receptor for the inhibitory neurotransmitter ‘GABA (Gamma-Aminobutyric Acid)’. This cluster has been found to be associated with the α5 subunit of the GABAA receptor and was hence named the GABRA5 cluster.

In a diet-induced obese mouse model, the researchers observed significant slowing in the pacemaker firing of the GABRA5 neurons. Researchers continued with the study by attempting to inhibit the activity of these GABRA5 neurons using chemogenetic methods. This in turn caused a reduction in heat production (energy consumption) in the brown fat tissue, leading to fat accumulation and weight gain. On the other hand, when the GABRA5 neurons in the hypothalamus were activated, the mice were able to achieve a successful weight reduction. This suggests that the GABRA5 neurons may act as a switch for weight regulation.

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Researchers at Baylor College of Medicine have developed a new compound called d16 that can reduce tumor growth and overcome therapeutic resistance in mutant p53-bearing cancers in the lab. The findings, published in the journal Cancer Research Communications, a journal of the American Association for Cancer Research, open opportunities for new combination therapies for these difficult-to-treat cancers.

“One of the most common alterations in many human cancers is mutations in p53, a gene that normally provides one of the most powerful shields against tumor growth,” said first author, Dr. Helena Folly-Kossi, a postdoctoral associate in Dr. Weei-Chin Lin’s lab at Baylor. “Mutations that alter the normal function of p53 can promote tumor growth, cancer progression and resistance to therapy, which are associated with poor prognosis. It is important to understand how p53 mutations help cancer grow to develop therapies to counteract their effects.”

Studying how to target p53 mutations that promote cancer growth has been difficult. “One of the challenges has been to develop drugs that act on mutant p53 directly. Some of these drugs are under development, but they appear to be toxic,” said Lin, professor of medicine-hematology and oncology and of molecular and cellular biology. He also is a member of Baylor’s Dan L Duncan Comprehensive Cancer Center and the corresponding author of the work.

The animal looked and barked like a dog—albeit one with long, pointed, foxlike ears—but it also climbed bushes, a behavior more typical of the local Pampas fox, and it refused common dog food, preferring to eat rats.

Caretakers began to wonder if it might be a hybrid—a mixture of domestic dog and some local wild canid. They contacted geneticists Thales Renato Ochotorena de Freitas from the Universidade Federal do Rio Grande do Sul and Rafael Kretschmer from the Universidade Federal de Pelotas who, last month, published a study confirming the animal was the world’s first documented fox-dog. The finding excited and intrigued experts in animal genetics.

“What a strange hybrid beast!” wrote Roland Kays, a biologist with North Carolina State University and the North Carolina Museum of Natural Sciences, on X (formerly Twitter), alongside a photo of the creature and link to the study.

Philosophers have wrestled with the question of whether we are truly free to decide on our actions for centuries. Now, insights from genetics, neuroscience and evolutionary biology are shedding fresh light on the issue.

By Clare Wilson