It is well established that both right before and after birth, new nerve cells (neurons) are generated at an important rate throughout the human brain. This process, called “neurogenesis”, supports development of the brain’s intricate structures, myriad connections and establishment of its communication network. In the late 1990s, scientists demonstrated something that many brain scientists thought impossible: that new neurons are also born during adulthood—in fact throughout the span of a healthy person’s life—but the role and function of these new neurons in a mature brain remains uncertain. In contrast to the neurogenesis during initial brain development, adult neurogenesis is restricted to a few brain areas, most notably, a structure called the dentate gyrus within the hippocampus.
A research team led by Lieber Institute for Brain Development (LIBD) Investigator Keri Martinowich, Ph.D. and including LIBD scientists Ronald McKay, Ph.D., Daniel Paredes, Ph.D., and Briony Catlow, Ph.D., sought to better understand the role of these new neurons in the adult brain. In a paper published May 2014 in Brain Structure & Function, the team reported that by using a genetic mouse model to observe what happened when adult neurogenesis was chronically suppressed, they found that important functions within the dentate gyrus were impaired that in turn influenced downstream hippocampal circuitry and activity that has been associated with stress-induced psychiatric illnesses.
“When levels of neurogenesis are abnormally low, whether because of chronic stress, or depression, or even normal aging, hippocampal atrophy appears to be one possible consequence. This furthers our understanding of the specific role neurogenesis plays in stress-induced hippocampal pathology that contributes to some psychiatric illnesses.”
The team built upon prior research that has shown that elevated levels of stress hormones in the brain, caused by chronic stress, leads to lower levels of newly generated neurons in the adult hippocampus. The team also knew the hippocampus is highly sensitive, and is prone to become atrophied in response to insults like stress. Such atrophy has been reversed in animals using pharmacological treatments that inhibit receptors for the excitatory neurotransmitter glutamate, which has led to the theory that the atrophy is caused by sustained glutamate overstimulation.
The team’s experimental suppression of neurogenesis in adult mice resulted in a retraction and remodeling of dendrites—arbor-like connections between excitatory (pyramidal) neurons—that caused atrophy in a section of the hippocampus called CA3. They also observed a corresponding increase in stress-induced release of glutamate, supporting the theory that atrophy is associated with overstimulation of glutamate.
Dr. Martinowich says that the team’s findings shed further light on the role of adult neurogenesis and the role it may play in both development of, and resilience from, stress-induced psychiatric illness. “This work suggests that newly born hippocampal neurons play an important role in regulating excitatory drive of the dentate gyrus, which has a major impact on overall hippocampal functioning,” she explained. “When levels of neurogenesis are abnormally low, whether because of chronic stress, or depression, or even normal aging, hippocampal atrophy appears to be one possible consequence. This furthers our understanding of the specific role neurogenesis plays in stress-induced hippocampal pathology that contributes to some psychiatric illnesses. The data, she concludes, also help explain how treatments that increase neurogenesis might be effective in countering stress-induced brain pathology.”