We humans lose mental sharpness as an unfortunate side effect of aging. And for individuals with neurodegenerative diseases such as Alzheimer’s and Parkinson’s, loss of cognitive function, often accompanied by mood disorders such as anxiety, is a harrowing experience. One way to combat cognitive decline and anxiety is to stimulate the formation of new neurons. For the first time, University of North Carolina Medical School scientists have targeted a specific type of neuron in mice to increase production of neural stem cells and induce the formation of new adult neurons to influence behaviour.
Targeting these cells as reported in the magazine natural neuroscienceand modified memory retrieval and altered anxiety-like behaviors in mice. Essentially, the University of North Carolina scientists boosted electrical activity between cells in the hypothalamus and hippocampus to create new neurons — an important process called neurogenesis.
“Targeting hypothalamic neurons to promote neurogenesis in the hippocampus in adults will not only benefit brain function,” said senior author Juan Song, Ph. disturbances”.
Most of the neurons we carry around for life are created before we are born and are organized during early childhood. But this neural formation persists into adulthood and throughout life. In fact, one of the causes of cognitive decline, anxiety, and even diseases like Alzheimer’s, is the cessation of neurogenesis.
Song, a member of the United Nations University’s Center for Neuroscience, has been studying the detailed interaction between brain cells that maintain neurogenesis. She knew that neurogenesis in the hippocampus in adults plays a critical role in processing memory and emotion, and that the activity of the neural circuit — thinking about “electrical activity” — regulates this process in an ever-changing way.
What no one knew was whether this neural circuit activity could be manipulated to stimulate neurogenesis so much that the effect would be seen as altered behaviour, such as improving memory or reducing anxiety.
To see the effect of modulating neural activity, Song’s lab conducted experiments led by co-authors Ya Dong Li, Ph.D., and Yan Jia Lu, Ph.D., both postdoctoral fellows. They used optogenetics — essentially a method that uses light to stimulate neuron activity — in a small brain structure called the supra-mammary nucleus (SuM). SuM is located within the hypothalamus in the brain. Helps manage things from perception to movement and sleep/wakefulness.
When the Song researchers chronically stimulated SuM neurons, they discovered a strong enhancement of neurogenesis at multiple stages. They have observed increased production of neural stem cells and the creation of new born neurons with enhanced properties. Then optogenetic stimulation of these new neurons altered memory and anxiety-like behaviours.
“We also show that SuM neurons are highly responsive when mice have experienced new things in their environment,” Song said. “In fact, in a new environment, mice require these cells to form neurons.”
Adult hippocampal neurogenesis is associated with many pathological conditions, such as aging, neurodegenerative diseases, and mental disorders. Song added, “Therefore, targeting hypothalamic neurons to promote neurogenesis in the hippocampus in adults will not only benefit brain function, but also hold the potential to treat cognitive and emotional defects associated with various brain disorders.”
Other authors are Zi Ka Chin, Luis Quintanilla and Lipu Zhang at UNC-Chapel Hill; Yuan Shiras and Michael Lazarus of the University of Tsukuba, Japan; and Zhi-Li Huang of Fudan University, China.
Alzheimer’s brain regeneration
Ya-Dong Li et al, hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior, natural neuroscience (2022). DOI: 10.1038 / s41593-022-01065-x
Provided by University of North Carolina Healthcare
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