How to Boost Neuron Production

Researchers at the University of Illinois Chicago have discovered that increasing the production of new neurons in mice with Alzheimer’s disease (AD) rescues the animals’ memory defects. The study, published in the Journal of Experimental Medicine (JEM), shows that new neurons can incorporate into the neural circuits that store memories and restore their normal function, suggesting that boosting neuron production could be a viable strategy to treat AD patients.

New neurons are produced from neural stem cells via a process known as neurogenesis. Previous studies have shown that neurogenesis is impaired in both AD patients and laboratory mice carrying genetic mutations linked to AD, particularly in a region of the brain called the hippocampus that is crucial for memory acquisition and retrieval.

Boosting neurogenesis increases the number of newly formed  neurons involved in storing  and retrieving memories (arrows) in the hoppocampus of mice with Alzheimer’s

However, the role of newly formed neurons in memory formation, and whether defects in neurogenesis contribute to the cognitive impairments associated with AD, is unclear,” says Professor Orly Lazarov of the Department of Anatomy and Cell Biology in the University of Illinois Chicago College of Medicine.

In the new JEM study, Lazarov and colleagues boosted neurogenesis in AD mice by genetically enhancing the survival of neuronal stem cells. The researchers deleted Bax, a gene that plays a major role in neuronal stem cell death, ultimately leading to the maturation of more new neurons. Increasing the production of new neurons in this way restored the animals’ performance in two different tests measuring spatial recognition and contextual memory.

By fluorescently labeling neurons activated during memory acquisition and retrieval, the researchers determined that, in the brains of healthy mice, the neural circuits involved in storing memories include many newly formed neurons alongside older, more mature neurons. These memory-stowing circuits contain fewer new neurons in AD mice, but the integration of newly formed neurons was restored when neurogenesis was increased.

Further analyses of the neurons forming the memory-storing circuits revealed that boosting neurogenesis also increases the number of dendritic spines, which are structures in synapses known to be critical for memory formation, and restores a normal pattern of neuronal gene expression.

Lazarov and colleagues confirmed the importance of newly formed neurons for memory formation by specifically inactivating them in the brains of AD mice. This reversed the benefits of boosting neurogenesis, preventing any improvement in the animals’ memory.

Our study is the first to show that impairments in hippocampal neurogenesis play a role in the memory deficits associated with AD by decreasing the availability of immature neurons for memory formation,” Lazarov says. “Taken together, our results suggest that augmenting neurogenesis may be of therapeutic value in AD patients.

Source: https://www.eurekalert.org/

Ultrasound Therapy for Alzheimer’s

One promising possibility when it comes to treating Alzheimer’s is the idea of using non-invasive ultrasound to take out toxic brain plaques, and a group of researchers in Australia have been at the cutting edge of this technology for a number of years. The scientists’ latest investigations have uncovered some surprising new ways this technique can improve cognition in mouse models of the disease, which they believe could have wider implications for restoring cognition in the elderly.

Led by Professor Jürgen Götz at the University of Queensland, the researchers behind this promising ultrasound therapy published some exciting early results in 2015. Initially, the idea was to use ultrasound in combination with gas-filled microbubbles to temporarily open the blood-brain barrier to allow in drugs that take out toxic amyloid and tau brain plaques that destroy synapses and are seen as key drivers of Alzheimer’s disease.

As it turned out, this technique proved an effective way to clear away the brain plaques without the need for any drugs, with the ultrasound activating microglial cells that could digest the plaques all on their own. The scientists then published a study in 2018 demonstrating how this technique could safely clear the toxic brain plaques and restore memory function in mouse models resembling human brains of 80 to 90 years old, and set their sights on human trials.

As they’ve continued to study this technique in mice, the scientists have continued to uncover new information about its effects on the brain, and how it might boost cognition. In newly published research, the team carried out new experiments on mouse models of brains with age-related deterioration, and found that it brought about yet further unexpected changes.

One of the physiological hallmarks of age-related cognitive decline is a deterioration in a type of signaling between neurons called long-term potentiation (LTP), which is associated with memory. The scientists were able to show that combining ultrasound with the microbubbles fully restored LTP in one region of the hippocampus. More interesting still, the ultrasound proved even more effective without the help of the microbubbles, not only restoring LTP but also improving the spatial learning deficits of the elderly mice by improving synaptic signaling and neurogenesis, among other physiological alterations.

Ultrasound may be a way to not just tackle brain plaques associated with Alzheimer’s, but also age-related cognitive decline in the broader population

The team’s ultrasound technique could serve as a two-pronged attack on Alzheimer’s, combining with microbubbles and plaque-busting agents to tackle the condition while simultaneously improving cognition via a separate pathway. And promisingly, the scientists believe the technique may one day prove a viable way to address age-related cognitive decline in the broader population.

Historically, we have been using ultrasound together with small gas-filled bubbles to open the almost-impenetrable blood-brain barrier and get therapeutics from the bloodstream into the brain,” Professor Götz says. “The entire research team was surprised by the remarkable restoration in cognition. We conclude therapeutic ultrasound is a non-invasive way to enhance cognition in the elderly.”

Source: https://qbi.uq.edu.au/

Gut Microbiome Unlocks The Secrets Of Aging

A new study has shown how the gut microbiota of older mice can promote neural growth in young mice, leading to promising developments in future treatments. The research group, based in Nanyang Technological University (NTU) in Singapore, transferred the gut microbiota of older mice into the gut of younger mice with less developed gut fauna. This resulted in enhanced neurogenesis (neuron growth) in the brain and altered aging, suggesting that the symbiotic relationship between bacteria and their host can have significant benefits for health.

The past 20 years have seen a significant increase in the amount of research into the relationship between the host and the bacteria that live in or on it. The results of these studies have established an important role for this relationship in nutrition, metabolism, and behavior. The medical community hopes that these latest results could lead to the development of food-based treatment to help slow down the aging process.

In this study, the research team attempted to uncover the functional characteristics of the gut microbiota of an aging host. The researchers transplanted gut microbiota from old or young mice into young, germ-free mouse recipients.

Using mice, the team led by Professor Sven Pettersson from the NTU Lee Kong Chian School of Medicine, transplanted gut microbes from old mice (24 months old) into young, germ-free mice (6 weeks old). After eight weeks, the young mice had increased intestinal growth and production of neurons in the brain, known as neurogenesis.
The team showed that the increased neurogenesis was due to an enrichment of gut microbes that produce a specific short chain fatty acid, called butyrate.
 We’ve found that microbes collected from an old mouse have the capacity to support neural growth in a younger mouse,” said Prof Pettersson. “This is a surprising and very interesting observation, especially since we can mimic the neuro-stimulatory effect by using butyrate alone.”
 “These results will lead us to explore whether butyrate might support repair and rebuilding in situations like stroke, spinal damage and to attenuate accelerated ageing and cognitive decline”.
The study was published in Science Translational Medicine, and was undertaken by researchers from Singapore, UK, and Australia.

Source: https://media.ntu.edu.sg/
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 https://www.medicalnewstoday.com/