much of the research on the underlying causes of Alzheimer's disease focuses on the beta amyloid (Aβ), a protein that accumulates in the brain as the disease progresses. The excess protein Aβ form groups or ‘plates’ that disrupt the communication between brain cells and trigger inflammation, which ultimately leads to a widespread loss of neurons and brain tissue.
The plates Aβ are a major focus for researchers of alzheimer's disease. However, a new work of neuroscientists from the University of Chicago (USA), conducted by the researcher in Spanish Sylvia Ortega-Martínez , reveals a new process involved in this pathology that, in the future, it could become a pharmacological target: the microglia.
Her work, published in the "Journal of Neuroscience" shows how, in the genetic forms of alzheimer's disease, a process called neurogenesis-can be interrupted by the own immune cells of the brain. "These results open a new avenue of research, highlighting the role of microglia in the brain's ability to generate new neurons (neurogenesis), key to the proper functioning of the brain. This new path of investigation, like all those developed in the field, has the final goal to better understand a disease due to various causes, and, consequently, to be able to get closer, each day more, to a potential therapy, and open a line of hope to patients and families of alzheimer's disease".
The project had as objective to evaluate the impact of the depletion of the microglia (a type of immune cell in the brain that usually repairs the synapses, destroys the dying cells and removes the excess protein Aβ) in models of Alzheimer's disease, in the processes of neurogenesis and anxiety. To do this, he explains to ABC Health researcher Spanish " we have used three different types of models of alzheimer's disease, all of them associated with mutations in the human gene for the presenilin 1 (PS1). These mutations in humans produce what is called 'familial Alzheimer's disease early onset' which amounts to between 1-5% of all cases of alzheimer's disease".
previous Research had shown that when healthy mice are placed in an environment ‘rich’ where they can exercise, play and interact between them, they have a huge increase in new brain cells that are created in the hippocampus, the part of the brain that is important for memory. But when mice carrying mutations in PS1 and PS2 are placed in such an environment, they do not show the same increase in new brain cells. They also begin to show signs of anxiety, a symptom often reported by people with alzheimer's disease of early onset.once you remove the microglia, all of these deficits present in the mice was restored completely. You delete a type of cell and everything's back to normal
The researchers focused on the microglia. When administered to mice a drug that causes microglial cells to die, neurogenesis returned to normal. Mice with mutations of presenilin were placed in an enriched environment and were well; showed no memory deficits or signs of anxiety, and they were creating the normal amount and expected of new neurons.
"it Is the most surprising result for me," says Sangram Sisodia, professor of Neurosciences at the University of Chicago. "Once you eliminate the microglia, all of these deficits present in the mice was restored completely. You delete a cell-type-and everything goes back to normal."
How? " We used a receptor antagonist CSFR1 in the food of the animals . To incorporate such a drug, known as PLX5622, we get a reduction of microglia in the 99%. In these cases, when we evaluate the neurogenesis and anxiety in the models studied, we saw that both pathological conditions are recovered, achieving a state similar to the control," explains the expert Spanish.
does that Mean that the microglia is a novel pharmacological target for this disease? Ortega-Martínez believes that the microglia is postulated as an important pharmacological target. "To be more precise –he adds-, the target is not the microglia itself, but the neurogenic cells, which are crucial for diseases such as alzheimer's disease and many other neurodegenerative (párkinson, etc) and psychiatric (depression, anxiety, schizophrenia, etc)".
In this sense, he says, the research aims to see what factors can we modify to get the neurogenesis hippocampal adult is not diminished in this group of diseases. "It is known that a decrease in neurogenesis is associated with cognitive problems (lack of memory, learning, etc), but also with emotional problems. Long-term –notes-, the ability to control neurogenesis could assume the power to control these diseases."
Well, forward, the question is to know specifically if it is the microglia that directly affects adult neurogenesis or if you are one of the factors that microglia secreted in the niche where the cells neurogenicas are. " This is the main question to address now in this project ".Our group combines both approaches to the disease. The jump to studies translational in humans rests primarily on the success seen in studies of basic research
The researcher points out that there are many groups working on alzheimer's disease and neurogenesis, and others on microglia and neurogenesis. "Our group combines both approaches to the disease. The jump to studies translational in humans rests primarily on the success seen in studies of basic research".
But for the moment, concludes, "we can only say that the removal of microglia in models of alzheimer's disease, family, studying two mutations key to this type of alzheimer's disease, has reversed the negative effects on both neurogenesis as anxiety. Now get to work on extending these studies to other models of alzheimer's disease, and other diseases of the nervous system, to potentially in the future, getting to human".
But remember that the main problem of this disease is that it is multicasual, hence the research must be to put limitations to his approach. "As metaphor, you could say that there are plenty of research groups working on Alzheimer's worldwide, and each one focuses on a particular aspect of the disease to unravel the puzzle or mosaic global disease".Updated Date: 21 September 2019, 03:01