Increased neuron formation restores memory in mice with Alzheimer’s disease

Summary: Increasing neurogenesis by deleting the Bax gene in mouse models of Alzheimer’s improved the animals’ performance on tests measuring spatial recognition and contextual memory.

Source: Rockefeller University

Researchers at the University of Illinois at Chicago have found that increasing the production of new neurons in mice with Alzheimer’s disease (AD) rescues the animals’ memory defects.

The study, which will be published on August 19 in Journal of Experimental Medicineshows that new neurons can be incorporated into neural circuits that store memories and restore their normal function, suggesting that increasing neuron production could be a viable strategy for treating AD patients.

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

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

In the new study, Lazarov and colleagues increased neurogenesis in AD mice by genetically enhancing the survival of neural stem cells. The researchers deleted Bax, a gene that plays an important role in the death of neural stem cells, 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.

The new study shows that increasing neurogenesis increases the number of newly formed neurons involved in storing and retrieving memories (arrows) in the hippocampus of AD mice. Credit: Mishra et al.

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 along with older, more mature neurons.

These memory storage circuits contain fewer new neurons in AD mice, but the integration of newly formed neurons was restored when neurogenesis was increased.

Further analyzes of the neurons that form the memory storage circuits revealed that increasing neurogenesis also increases the number of dendritic spines, which are structures at synapses known to be critical for memory formation, and restores a normal pattern of neuronal gene expression.

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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 increasing 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,” says Lazarov.

“Together, our results suggest that increasing neurogenesis may have therapeutic value in AD patients.”

About this neurogenesis and Alzheimer’s disease research news

Author: Press Office
Source: Rockefeller University Press
Contact: Press Office – Rockefeller University Press
Image: Image is credited to Mishra et al

Original research: Findings will appear in Journal of Experimental Medicine

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