Groundbreaking Study: Researchers Reverse Cognitive Decline in Alzheimer’s Mice Model, Opens Door for New Treatment
Individuals with Alzheimer’s disease often experience impairments in cognitive functions, such as memory, as well as noncognitive functions, which can lead to feelings of anxiety and depression.
In a study published in the journal Cell Stem Cell today, researchers utilized mice to examine adult hippocampus neurogenesis (AHN), a process in which new neurons are generated during adulthood.
The study demonstrated that deep brain stimulation of newly-formed neurons aided in restoring both cognitive and noncognitive functions in mouse models of Alzheimer’s disease.
Senior author Juan Song says, they “were surprised to find that activating only a small population of adult-born new neurons was enough to make a significant contribution to these brain functions.”
Deep brain stimulation was used to modify the neurons in the supramammillary nucleus (SuM), which is situated in the hypothalamus.
“We are eager to find out the mechanisms that underlie these beneficial effects,” Song adds.
The study utilized two separate mouse models of Alzheimer’s disease. The researchers employed optogenetics to stimulate the supramammillary nucleus (SuM) and enhance adult hippocampus neurogenesis (AHN) in mice with Alzheimer’s disease. Previous research conducted by the team demonstrated that SuM stimulation could increase the generation of new neurons and improve their characteristics in normal adult mice. The current study exhibited that this approach was also effective in mice with Alzheimer’s disease, resulting in the formation of new neurons that formed better connections with other brain regions.
Merely having more and improved new neurons is insufficient to enhance memory and mood. In Alzheimer’s mice, behavioral improvement was observed only when these enhanced new neurons were activated through chemogenetics.
The team employed memory tests and established assessments to identify anxiety-like and depression-like behavior and verify these enhancements. The findings imply that a multi-level enhancement of new neurons, including increased numbers, enhanced properties, and activity, is necessary to restore behavior in Alzheimer’s brains.
In order to gain a deeper understanding of the underlying mechanism, they also investigated the protein changes in the hippocampus of Alzheimer’s mice following the activation of SuM-modified new neurons. Their analysis revealed the activation of various protein pathways that are known to play a crucial role in improving memory function and enabling the clearance of Alzheimer’s-related plaques.
“It was striking,” adds Song, “that multilevel enhancement of such a small number of adult-born new neurons made such a profound functional contribution to the animals’ diseased brains.”
They “were also surprised to find that activation of SuM-enhanced neurons promoted the process that can potentially remove plaques.”
The team’s future endeavors will concentrate on creating potential therapeutics that can replicate the advantageous effects brought about by the activation of new neurons modified by SuM.
“We are hoping these drugs could exert therapeutic effects in patients with low or no hippocampal neurogenesis,” Song adds. “Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat Alzheimer’s and related dementia.”
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