Study might provide new clues to designing better treatments for depression and other neuropsychiatric disorders
Cold Spring Harbor, NY — Shooting steady pulses of electricity through slender electrodes into a brain area that controls complex behaviors has proven to be effective against several therapeutically stubborn neurological and neuropsychiatric disorders. Now, a new study has found that this technique, called deep brain stimulation (DBS), targets the same class of neuronal cells that are known to respond to physical exercise and drugs such as Prozac.
The study, led by Associate Professor Grigori Enikolopov, Ph.D., of 黑料吃瓜资源 (CSHL), is the cover story in the January 1 issue of The Journal of Comparative Neurology, which is currently available online.
The targeted neuronal cells, which increase in number in response to DBS, are a type of precursor cell that ultimately matures into adult neurons in the brain鈥檚 hippocampus, the control center for spatial and long-term memory, emotion, behavior and other functions that go awry in diseases such as Alzheimer鈥檚, Parkinson鈥檚, epilepsy and depression. DBS has been successful in treating some cases of Parkinson鈥檚. And recently, it has also proven to work against other brain disorders such as epilepsy and severe depression.
鈥淏ut the clinical application of DBS to treat neuropsychiatric disorders is still problematic because there isn鈥檛 a clear rationale or a guide for which brain regions need to be stimulated to achieve maximum therapeutic benefit,鈥� says Enikolopov. 鈥淥ur study now points to the brain region whose stimulation results in new cell growth in the hippocampus, an area that is implicated in many behavioral and cognitive disorders.鈥�
Enikolopov has long been interested in understanding how neuronal and neuroendocrine circuits are involved in mood regulation. 鈥淭o that end, the question we鈥檝e been asking is whether different types of stimuli, such as exercise or drugs or DBS, target different types of brain cells and circuits or converge on the same targets,鈥� he explains.
鈥淭here is a well-established correlation between the use of antidepressants and new neuronal growth in the hippocampus,鈥� says Enikolopov. 鈥淏ut what we didn鈥檛 know was which steps in the cascade of events that eventually leads to the birth of new neurons are actually affected.鈥� Brain stem cells eventually differentiate into mature neurons following a cascade of steps, each of which produces a different intermediary cell type or precursor.
To identify the specific cell type affected by DBS, the CSHL team developed mouse models in which different classes of neural cells such as stem and progenitor cells produce different fluorescent colors. This enabled the scientists to visually track these cell populations and quantitatively assess how they change in response to neuronal triggers such as DBS.
To examine the effect of DBS on the hippocampus, Enikolopov teamed up with Andres Lozano, M.D., a leading Canadian neurosurgeon who pioneered its use against depression. The scientists found that stimulating the anterior thalamic nucleus—an area in the mouse brain that is equivalent to a human brain area where DBS is often therapeutically applied—resulted in an increase in cell division among the neural stem and progenitor cells, which in turn manifested as an increase in the number of new adult neurons in the hippocampus.
鈥淏y tracking new cell growth in the hippocampus and using it as a sensitive readout, we could potentially pinpoint other brain sites at which therapeutic DBS or other stimuli such as drugs might work best for various neurological and psychiatric conditions,鈥� explains Enikolopov.
Written by: Hema Bashyam, Science Writer | [email protected] | 516-367-8455
Citation
鈥淣eurogenic hippocampal targets of deep brain stimulation鈥� appears in the January 1issue of the Journal of Comparative Neurology. The full citation is: Juan M. Encinas, Clement Hamani, Andres M. Lozano, and Grigori Enikolopov. The paper is available online at