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Boosting neuron formation may restore memory in Alzheimer’s patients

Increasing the formation of neurons in the hippocampus restored the memory function in mice with familial Alzheimer’s disease.

(CN) — Anyone who has witnessed Alzheimer’s disease firsthand knows its devastating effects on health and connection to loved ones. As the most common cause of dementia, the neurodegenerative disease slowly invades memories without notice, causing those affected to forget their friends, family, environment and even their sense of self.

But while Alzheimer’s has been long thought to be incurable, researchers are developing new ways to tap into neural circuits to restore memory function in mice — bringing hope that potential therapies are on the horizon.

In new study published Friday in the Journal of Experimental Medicine, researchers at the University of Illinois Chicago revealed they have discovered a functional link between hippocampal neurogenesis — the production of new neurons or nerve cells in the hippocampus region of the brain — and the restoration of memory function in mice.

“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 function,” study author Orly Lazarov, professor in the department of anatomy and cell biology at UIC’s College of Medicine, said in a statement accompanying the study. “Taken together, our results suggest that augmenting neurogenesis may be of therapeutic value in AD patients.”

Alzheimer’s disease is characterized by progressive loss of memory and cognitive function. The disease has no cure and only a limited number of treatments exist. Medications like aducanumab can remove amyloid — abnormal aggregates of proteins associated with the disease — to reduce cognitive and functional decline.

“Other treatments can temporarily slow the worsening of dementia symptoms and improve quality of life for those with Alzheimer's and their caregivers,” the Alzheimer’s Society website says. Still, the mechanism underlying memory loss is largely unknown.

What is known by researchers, however, is that the denate gyrus region of the hippocampus plays a unique role for neurogenesis. It is within this region that neural stems cells differentiate into new neurons that participate in circuits involving memory acquisition, retrieval, conditioned-fear responses and spatial memory networks.

The role of immature neurons in memory formation is yet to be fully understood, Lazarov said, although the study indicates these neurons are actively recruited into the engram — where memories are imprinted — following a hippocampus-dependent task like finding an object in a maze.

To boost neurogenesis, researchers genetically enhanced the survival of neuronal stem cells by deleting BAX — a gene that plays a major role in neuronal stem cell death — to bring the maturation of new neurons. Enhancing the production of new neurons in this way restored the mice’s performance in tests measuring spatial recognition and contextual memory.

Using fluorescent labels on activated neurons during memory acquisition and retrieval, researchers were able to determine healthy mice undergoing neurogenesis experienced improved neural circuits with many new neurons alongside more mature ones. The same memory-storing circuits in mice with Alzheimer’s contained fewer neurons, but integration of newly formed neurons restored after neurogenesis increased.

Further analysis of memory-storing circuits also revealed that boosting neurogenesis increases the number of dendritic spines — structures of synapses critical to memory formation — and restores a normal pattern of neuronal gene expression. Researchers confirmed this finding by deactivating newly formed neurons in mice with Alzheimer’s, reversing the benefits of increasing neurogenesis and preventing further memory improvement.

Along with discovering three genes most expressed in the engram, “these observations suggest that defective neurogenesis contributes to memory failure in [Alzheimer’s disease],” the study authors wrote.

Even so, experts in the field of Alzheimer’s are wary of celebrating too soon.

 “This research is interesting and adds to our understanding of how memories are formed and lost in the brain,” wrote Alzheimer’s Association director of scientific engagement Dr. Percy Griffin in an email. “Neurons in most areas of the brain usually don’t divide so they can be easily replaced once they’re gone.”

Griffin added: “While intriguing, this research is in mice. If we want to take advantage of this to help humans, we need to find safe ways of generating new neurons in the adult human brain. The Alzheimer’s Association supports new ideas in Alzheimer’s research and encourages innovative work like this to continue.”

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Categories / Health, Science

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