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/

Genes Behind Humankind’s Big Brain

Scientists have pinpointed three genes that may have played a pivotal role in an important milestone in human evolution: the striking increase in brain size that facilitated cognitive advances that helped define what it means to be human. These genes, found only in people, appeared between 3 and 4 million years ago, just prior to a period when the fossil record demonstrates a dramatic brain enlargement in ancestral species in the human lineage, researchers said. The three nearly identical genes, as well as a fourth nonfunctional one, are called NOTCH2NL genes, arising from a gene family dating back hundreds of millions of years and heavily involved in embryonic development. 

The NOTCH2NL genes are particularly active in the reservoir of neural stem cells of the cerebral cortex, the brain’s outer layer responsible for the highest mental functions such as cognition, language, memory, reasoning and consciousness. The genes were found to delay development of cortical stem cells into neurons in the embryo, leading to the production of a higher number of mature nerve cells in this brain region.

The cerebral cortex defines to a large extent what we are as a species and who we are as individuals. Understanding how it emerged in evolution is a fascinating question, touching at the basic origins of mankind,” said developmental neurobiologist Pierre Vanderhaeghen of Université Libre de Bruxelles and VIB/KULeuven in Belgium.

It is the ultimate evolutionary question and it is thrilling to work in this area of research,” added biomolecular engineer David Haussler, scientific director of the University of California, Santa Cruz Genomics Institute and a Howard Hughes Medical Institute investigator.

Source: https://www.reuters.com/