Scientists delete a gene to restore memory!

Alzheimer’s disease, progressive memory loss

Alzheimer’s disease, which affects one in five people over the age of 80, is a neurodegenerative disease characterized by progressive and irreversible loss of memory and intellectual functions. The best-known symptoms of this condition are language disorders, gestural difficulties, loss of recognition of people, objects and places, as well as difficulties adapting to certain situations.

The mild stage of Alzheimer’s disease is characterized by mild and difficult to identify symptoms. The person remains fully conscious, but has mild memory loss and difficulty learning new things. When the moderate stage of the disease begins, the person begins to need more help with daily tasks and the symptoms are more and more noticeable. Cognitive decline sets in gradually and memory deteriorates. The disease then progresses to an advanced stage in which the patient barely knows how to express themselves and take care of themselves. Memory problems are serious at this stage. The patient can no longer walk alone and needs help to go to the bathroom. He needs help daily. During the last months of life of a patient affected by this condition, cognitive and physical abilities deteriorate very quickly. The accompaniment then focuses on palliative care to ensure the best possible quality of life and a dignified end.

Alzheimer’s disease remains fatal and incurable to this day. However, research is active to find effective treatments. Today, researchers at the University of Illinois in the United States have just achieved a breakthrough.

(Also read: Can you boost memory with games?)

Deletion of a gene implicated in neural stem cell death

Neurogenesis is a process in which neural stem cells give rise to cells that differentiate into neurons. Neural stem cells are cells capable of self-renewal, that is, they have the ability to reproduce rapidly to give rise to other neural stem cells. They are also characterized by their multipotent character, that is, they are capable of differentiating into neurons, but also into astrocytes and oligodendrocytes. Neurogenesis takes place in the olfactory bulb and in the hippocampus known for its role in memorization, behavior and management of certain emotions.

In patients with Alzheimer’s disease, neurogenesis is impaired primarily in the hippocampus. In this new research, the scientists used mice affected by Alzheimer’s disease in which they stimulated neurogenesis affected by the disease by deleting the Bax gene. The Bax gene is a nucleotide sequence whose expression allows the synthesis of a protein capable of inducing cell apoptosis, a process of cell self-destruction. Its suppression in mice has stimulated the formation of new neurons and restored the animals’ memory, among other things at the level of spatial recognition and contextual memory.

Using a fluorescence labeling process to detect neurons activated in the process of memory retrieval, the University of Illinois team realized that in healthy mice, the neural circuits involved in memory include many new neurons. In mice with Alzheimer’s disease, there are far fewer new neurons, except when neurogenesis is stimulated.

(Also read: Detect Alzheimer’s earlier thanks to a video game)

Stimulation of neurogenesis promotes the formation of dendritic spines

Neuron highlighted by silver chromate staining. The dendritic spines are clearly visible at the level of the dendrites. Source: Jose Luis Calvo

Looking in more detail at neuron formation during stimulation of neurogenesis, the researchers found that the number of dendritic spines also increased. Dendritic spines are protuberances present at the level of dendrites in certain neurons. They play an important role in synaptic function, that is, the transfer of nerve impulses through neuromediators. These structures are also active for neuronal plasticity, since they regularly change their “shape” and appear or disappear depending on the state of development of the neurons. The loss or reduction in the number of these dendritic spines in neurons leads to neurodegenerative pathologies and mental retardation.

In the magazine EurekAlert, Orly Lazarov, one of the scientists who participated in this study, states: “Our study is the first to show that impairments in hippocampal neurogenesis play a role in memory deficits associated with Alzheimer’s disease by decreasing the availability of immature neurons for memory formation. Taken together, our results suggest that increased neurogenesis may have therapeutic value in patients with Alzheimer’s disease.”

(Also read: Is Alzheimer’s disease hereditary?)

Font:

Rachana Mishra, Trongha Phan, Pavan Kumar, Zachery Morrissey, Muskan Gupta, Carolyn Hollands, Aashutosh Shetti, Kyra Lauren Lopez, Mark Maienschein-Cline, Hoonkyo Suh, Rene Hen, Orly Lazarov, “Increasing Neurogenesis Rescues Memory Impairments in Alzheimer’s disease by restoring neurons that store memory.” Journal of Experimental Medicine (JEM)August 19, 2022, https://doi.org/10.1084/jem.20220391

Leave a Reply

Your email address will not be published. Required fields are marked *