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Science On The Cutting Edge from page 16
Running Throughout Middle

Age Keeps “Old” Adult-Born Nobel Laureate Describes

Neurons “Wired” Dogma-Breaking Brain

By Gisele Galoustian Research
Aging often is
accompanied by Brain cells called
cognitive decline. microglia are known
Among the first to act as immune
structures of the brain sentries of the brain,
affected are the hippocampus and adjacent cortices, areas clearing debris and
essential for learning and memory. Deficits in cognitive during early adulthood, into a network that is relevant to the dead cells, and fighting
ability are associated with reduced hippocampal volume maintenance of episodic memory encoding during aging. infections. But
and degradation of synaptic connectivity between the “Long-term exercise profoundly benefits the aging controlling behavior?
hippocampus and the (peri)-entorhinal cortex. brain and may prevent aging-related memory function That wasn’t part of
Increasing evidence indicates that physical activity decline by increasing the survival and modifying the their job description.
can delay or prevent these structural and functional network of the adult-born neurons born during early Nobel Prize-
reductions in older adults. A new study by Florida Atlantic adulthood, and thereby facilitating their participation winning neurobiologist
University and CINVESTAV, Mexico City, Mexico, in cognitive processes,” said Henriette van Praag, Mario R. Capecchi,
provides novel insight into the benefits of exercise, which Ph.D., corresponding author, an associate professor Ph.D., visited The
should motivate adults to keep moving throughout their of biomedical science in FAU’s Schmidt College of Herbert Wertheim UF
lifetime, especially during middle age. Medicine and a member of the FAU Stiles-Nicholson Scripps Institute for
For the study, researchers focused on the effects of Brain Institute. Biomedical Innovation
long-term running on a network of new hippocampal Findings from the study showed long-term running and Technology on Thursday, delivering a gripping
neurons that were generated in young adult mice, at significantly increased the number of adult-born neurons lecture about how his team at the University of Utah
middle age. These “mice on the run” demonstrate that and enhanced the recruitment of presynaptic (sub)- discovered that a gene called Hoxb8 influences chronic
running throughout middle age keeps old adult-born cortical cells to their network. anxiety and OCD behaviors. Nobel Laureate Mario R.
neurons wired, which may prevent or delay aging-related “Long-term running may enhance pattern separation Capecchi, Ph.D., delivered a distinguished lecture at The
memory loss and neurodegeneration. ability, our ability to distinguish between highly similar Wertheim UF Scripps Institute on April 6.
events and stimuli, a behavior closely linked to adult “We are suggesting that microglia are controlling very
Long-ter m running neurogenesis, which is among the first to display deficits specific behaviors. They are talking to neurons, and the
substantially modifies the indicative of age-related memory decline,” said Carmen neurons are controlling behavior,” Capecchi said.
network of the neurons Vivar, Ph.D., corresponding author, Department of Part of the graduate program’s distinguished lecture
generated in young adult mice Physiology, Biophysics and Neuroscience, Centro de series, Capecchi’s talk described using the same mouse
upon middle-age. Importantly, Investigacion y de Estudios Avanzados del IPN in Mexico. genetics research methods that earned him the Nobel Prize
exercise increases input from Aging-related memory function decline is associated in 2007, bolstered by newer techniques for controlling
hippocampal interneurons with the degradation of synaptic inputs from the perirhinal the activity of cells, especially optogenetics. Blending
(red cells) onto “old” and entorhinal cortex onto the hippocampus, brain areas these and other methods helped his group show that the
adult-born neurons. These that are essential for pattern separation, and contextual gene transcription factor Hoxb8 influences OCD and
interneurons may play a role and spatial memory. anxiety behaviors in mice in a surprising way — not
in reducing aging-related “We show that running also substantially increases the within neurons, but within another group of brain cells,
hyperexcitability of the back-projection from the dorsal subiculum onto old adult- microglia.
hippocampus and thereby born granule cells,” said van Praag. “This connectivity His team found in 2017 that the brain is populated by
benefit memory function. may provide navigation-associated information and two lineages of microglia, those that have Hoxb8, about
Photo by Carmen Vivar, Ph.D. mediate the long-term running-induced improvement in 30 percent of the microglia, and those that do not, about
spatial memory function.” 70 percent. It appears that the two work in opposition to
Adult-born neurons are thought to contribute to Results from the study show that running not only suppress or accelerate anxiety behaviors.
hippocampus-dependent memory function and are rescued perirhinal connectivity but also increased and Despite being a Nobel laureate, Capecchi has found
believed to be temporarily important, during the so-called altered the contribution of the entorhinal cortices to the that breaking scientific dogma can provoke skepticism
“critical period” at about three to six weeks of cell age, network of old adult-born neurons. and even backlash. It drives him to conduct more
when they can fleetingly display increased synaptic “Our study provides insight as to how chronic research.
plasticity. However, these new neurons do remain present exercise, beginning in young adulthood and continuing “I have had people in the field literally insult me,” he
for many months, but it was unclear whether those born throughout middle age, helps maintain memory function told the students. “But the data is there.”
in early adulthood remain integrated into neural networks during aging, emphasizing the relevance of including Chronic anxiety affects more than 20 percent of
and whether their circuitry is modifiable by physical exercise in our daily lives,” said Vivar. the population, affecting more women than men.
activity in middle age. Study co-authors are Ben Peterson, Ph.D., currently Understanding the biology behind it is important, he
To address these questions, researchers used a a postdoc at University of California Davis; Alejandro stressed.
unique rabies virus-based circuit tracing approach with Pinto, FAU’s Schmidt College of Medicine and Stiles- The next stage of his research is investigating which
a long-time interval between the initial labeling of new Nicholson Brain Institute; and Emma Janke, a recent neurons interact with the microglia to direct the OCD-
neurons and subsequent analysis of their neural circuitry graduate of the University of Pennsylvania. like behaviors and anxiety, and then to discern how
in rodents. More than six months after tagging of the This research was supported in part by the FAU Stiles- the microglia transmit the signals, he said. There’s a
adult-born neurons with a fluorescent reporter vector, Nicholson Brain Institute and the Jupiter Life Sciences correlation with female hormones that needs further
they identified and quantified the direct afferent inputs Initiative (awarded to van Praag), and by the Fondo de explorations, he noted.
to these adult-born neurons within the hippocampus and Investigación Científica y Desarrollo Tecnológico del “Some neurons express estrogen and some don’t, so it
(sub) cortical areas, when the mice were middle-aged. Cinvestav (Proyectos SEP-Cinvestav), (awarded to Vivar). gives us a clue,” he said. “Once we know which neurons,
Results of the study, published in the journal eNeuro, we can do a lot more experiments.”
show long-term running wires “old” new neurons, born

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