27 Aug USC Study Finds Strong Correlation Between Estrogen-Reactive Hormones and Depressive States
MedicalResearch.com Interview with:
Huizhong Whit Tao, PhD
Professor of Physiology & Neuroscience
Zilkha Neurogenetic Institute
Department of Physiology & Neurosience
Keck School of Medicine
University of Southern California
MedicalResearch.com: What is the background for this study?
Response: Previously, we published a study in which we found that a group of neurons, namely glutamatergic neurons, in the medial preoptic area (MPOA) of the hypothalamus mediate stress-induced anxiety states. This result inspired us to explore whether the MPOA can play a more general role in mood regulation. Fluctuations in the productive hormones secreted by women’s ovaries are known to cause mood swings.
In some cases, rapid changes in the secretion of ovarian hormones can cause depressive-like symptoms. Key examples are postpartum and peri-menopausal depression. In this study, we intended to test whether the MPOA can also play a part in depressive states that are linked to fluctuations in ovarian hormones.
MedicalResearch.com: What are the main findings?
Response: In a female mouse model of ovarian hormone withdrawal (HW) that exhibits depressive-like behaviors, we carried out in vivo cell-type specific electrophysiological recordings and found that a group of GABAergic (but not glutamatergic) neurons, namely estrogen receptor expressing neurons, reduced their firing activity as compared to non-HW controls. Using optogenetics and chemogenetics to manipulate activity levels of these neurons, we found that artificially increasing the activity of these specific MPOA neurons alleviates the depressive state of HW-treated mice, while decreasing their activity in naïve non-treated mice induces depressive-like behaviors. In addition, we found that different depressive symptoms are mediated by divergent MPOA projections to distinct downstream targets, which are intimately linked to dopamine and serotonin releasing neurons in the midbrain.
MedicalResearch.com: What should readers take away from your report?
Response: Our study indicates a strong correlation between the activity level of MPOA GABAergic (in particular estrogen receptor expressing) neurons in the female mice brain and the manifestation of depressive states. This suggests that the MPOA may play a part in the depression-like symptoms that women sometimes experience at different points of the menstrual cycle, around menopause and after giving birth. Our findings have strong implications for developing therapeutical strategies to treat postpartum and perimenopausal depression. Since the MPOA neurons are upstream of the dopamine and serotonin releasing neurons, targeting these hypothalamic neurons may have a more potent effect than the current therapeutical approaches targeting serotonin or dopamine.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: How ovarian hormone withdrawal leads to activity changes in specific MPOA neurons is an intriguing question. We have inconclusive evidence that changes of some membrane ion channels may be an underlying cause. For future research, we will focus on identifying the affected membrane proteins. In addition, in the current study we did not find activity changes in the glutamatergic MPOA neurons in HW-treated mice. As depressive states can be induced under a variety of different circumstances, we will further investigate if the glutamatergic neurons can be affected by some other treatments, for example, early life stress.
We do not have any disclosures.
Tao, C., Zhang, GW., Huang, J.J. et al. The medial preoptic area mediates depressive-like behaviors induced by ovarian hormone withdrawal through distinct GABAergic projections.
Nat Neurosci (2023). https://doi.org/10.1038/s41593-023-01397-2
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