Targeting specific brain cells with electrical boosts stimulated neurogenesis and created new neurons.
One of the unfortunate side effects of aging is the loss of mental acuity – and for individuals with neurodegenerative conditions such as Alzheimer’s or Parkinson’s, the loss of cognitive function is often accompanied by mood disorders such as anxiety. This can be a harrowing experience, but one way to push back against cognitive decline and anxiety would be to encourage the creation of new neurons.
Longevity.Technology: Now scientists at the University of North Carolina School of Medicine have targeted a specific kind of neuron in mice to increase the production of neural stem cells and trigger the creation of new adult neurons to affect behaviour.
Writing in the journal Nature Neuroscience, the research team detail how, when they targeted these cells, they were able to modulate memory retrieval and alter anxiety-like behaviours in mice. In a scientific nutshell, the UNC researchers boosted the electrical activity between cells in the hypothalamus and the hippocampus to create new neurons –the key process of neurogenesis.
“Targeting the hypothalamic neurons to enhance adult hippocampal neurogenesis will not only benefit brain functions,” said senior author Juan Song, PhD, associate professor of pharmacology, “but also holds the potential to treat cognitive and affective deficits associated with various brain disorders [1].”
Most neurons we carry for life were created before we were born; although they become organised during early childhood, the process of neurogenesis continues on into adulthood and throughout life. If neurogenesis does slow or stop, this contributes to cognitive decline and anxiety, and even to diseases such as Alzheimer’s.
Song, a member of the UNC Neuroscience Center, has been studying the detailed interplay between brain cells that keep neurogenesis process ticking along. It is known that adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and that neural circuit activity – the electrical activity in our brains regulates this process in a constantly changing manner.
What was not known, however, is whether this neural circuit activity could be manipulated to push neurogenesis on to such a degree that the effect would be seen as a changed behaviour, such as better memory or less anxiety.
To see the effect of modulating neural activity, the Song lab conducted experiments led by co-first authors Ya-Dong Li, PhD, and Yan-Jia Luo, PhD, both postdoctoral fellows. They used optogenetics – a method that uses light to trigger neuronal activity – in a small brain structure called supramammillary nucleus (SuM). The SuM is located inside the hypothalamus region of the brain, and it helps control various processes, from cognition to locomotion and from sleeping to wakefulness.
When the researchers chronically stimulated the SuM neurons, they discovered a robust promotion of neurogenesis at multiple stages. They observed increased production of neural stem cells and the creation of new adult-born neurons with enhanced properties. Optogenetic stimulation of these new neurons then altered memory and anxiety-like behaviours [2].
“We also show that the SuM neurons are highly responsive when the mice experienced new things in their environment,” Song said. “In fact, in a new environment, mice require these cells for neurogenesis [1].”
Impaired adult hippocampal neurogenesis correlates with many pathological states, such as aging, neurodegenerative diseases and mental disorders.
“Therefore,” Song added, “targeting the hypothalamic neurons to enhance adult hippocampal neurogenesis will not only benefit brain functions but also holds the potential to treat cognitive and affective deficits associated with various brain disorders [1].”
[1] https://news.unchealthcare.org/2022/05/
[2] https://www.nature.com/articles/s41593-022-01065-x
