A US research team has succeeded in restoring memory damaged by Alzheimer’s disease by manipulating the genes of mice, an animal model of Alzheimer’s disease, to generate more new brain neurons.
A team led by Professor Orly Lazarov of the Department of Anatomy and Cell Biology at the University of Illinois at Chicago, USA, published a scientific journal ‘Journal of Experimental Medicine’ on the 21st to manipulate the gene of Alzheimer’s mice to make more neurons from neural stem cells. They found that impaired cognitive function and memory were restored in mice.
The research team found that newly created neurons are inserted into the neural circuits in the brain that are responsible for memory and function to restore memory. This suggests the possibility of becoming a possible treatment strategy.
In the brain, neural stem cells develop into new neurons through the process of ‘neurogenesis’. Previous studies have found that both Alzheimer’s disease patients and mice with Alzheimer’s-related genetic mutations have impaired neurogenesis in the hippocampus, an important brain region for memory acquisition and retrieval.
However, Professor Lazarov said, “What role the newly formed neurons play in memory, and how defects in neurogenesis affect cognitive impairment associated with Alzheimer’s disease, have not been clearly elucidated,” Lazarov said.
The research team removed the gene (Bax) that plays an important role in neural stem cell death in Alzheimer’s disease animal model mice so that more new neurons are made from the neural stem cells. An experiment was conducted to measure
As a result, it was confirmed that more new neurons were made in the hippocampus of Alzheimer’s mice, in which the Bax gene was removed.
In addition, these mice performed better in spatial cognitive function than the control group Alzheimer’s mice in an experiment in which they were placed in a new space to observe the behavior of their surroundings. It was found to have recovered to a level similar to that of these normal mice.
Next, the research team manipulated the neurons that are activated in the process of memory generation and retrieval to emit fluorescence and observed that the neural circuits that generate memories contain many newly created immature neurons along with old mature neurons. appear.
However, in the brain neural circuits of Alzheimer’s mice, newly generated immature neurons were much less than in healthy mice, and it was confirmed that the amount of immature neurons in the neural circuits was restored in the mice whose neurogenesis was restored by removing the Bax gene.
By further analyzing the memory-storage neural circuits, the research team found that promoting neurogenesis increases dendritic spines, synaptic structures known to be important for memory formation, and restores neural gene expression patterns to normal. In addition, it was confirmed that the effect of memory recovery disappears when the activity of newly formed neurons in the brain of Alzheimer’s mice is suppressed.
“This study is the first to show that impaired hippocampal neurogenesis plays an important role in Alzheimer’s disease-related memory decline by reducing the number of immature neurons required for memory formation,” said Professor Lazarov. It suggests that it may have therapeutic value for patients with the disease.”
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