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From Where Comes Depression?

Damian Zuloaga stands in his Biology Building laboratory. (Photo by Patrick Dodson)

ALBANY, N.Y. (April 24, 2019) — Studies around the world confirm that women are twice as likely as are men to be diagnosed with a form of depression or anxiety. The first question to be posed is “why?”

Studies conducted in the lab of UAlbany behavioral neuroscientist Damian Zuloaga are beginning to answer that question. Zuloaga and colleagues discovered a sex difference in a key cell type that is known to control anxiety and depression within two distinct brain areas in the mouse brain. The first of these areas, the anteroventral periventricular nucleus, was the subject of an article in the journal Neuroscience in October of 2017.

Zuloaga’s discovery of the sex differences revealed in the second area, the paraventricular hypothalamus, has just been accepted for a new article in Neuroscience.

The crucial follow-up question now becomes, “Are these cell groups truly important for controlling sex differences in anxiety and depression?”

That is what Zuloaga’s new three-year project, funded by the National Institutes of Mental Health for $462,000, will seek to positively determine. The assistant professor in Psychology has a good idea about how to address the challenge — and it involves the mouse.

“Our laboratory has recently discovered two cell groups in the hypothalamus and preoptic area of the mouse brain which show striking sex differences in the distribution of corticotropin-releasing hormone receptor 1 (CRFR1); a cell type known to regulate mood behaviors,” said Zuloaga. “We will perform experiments to determine the function of these sexually dimorphic cell groups and therefore fill a gap in knowledge regarding the specific brain regions that regulate sex differences in anxiety and depression.”

His proposed experiments will investigate the role of these two groups of CRFR1 cells in regulating anxiety and depressive behaviors by selectively destroying these cell groups in mice, through use of a toxin.

“Furthermore,” he said, “we will use viruses to determine how these sexually dimorphic cell populations are functionally connected to other areas of the brain that regulate stress-related behaviors.

“Finally, we will generate a mouse line that lacks a receptor for estrogen within CRFR1 cells to determine the mechanism through which sex hormones regulate stress-related behaviors."

The full title of the project is “Sex differences in corticotropin releasing factor receptor 1 regulation of stress-associated behaviors.” Andrew Poulos, also an assistant professor in Psychology, is Zuloaga’s collaborator on the project.

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