{"id":769,"date":"2018-12-19T23:35:24","date_gmt":"2018-12-19T23:35:24","guid":{"rendered":"https:\/\/wp.uthscsa.edu\/pharmacology\/?page_id=769"},"modified":"2018-12-19T23:35:24","modified_gmt":"2018-12-19T23:35:24","slug":"milena-girotti","status":"publish","type":"page","link":"https:\/\/lsom.uthscsa.edu\/pharmacology\/research-faculty\/milena-girotti\/","title":{"rendered":"Milena Girotti"},"content":{"rendered":"

[vc_row][vc_column width=”2\/3″][vc_column_text]<\/p>\n

Assistant Professor\/Research<\/span><\/h3>\n

Ph.D., Department of Biochemistry<\/span><\/p>\n

University of Bristol<\/span><\/p>\n

Bristol, England, U.K.<\/span><\/p>\n

Office:<\/strong> 210-567-5069<\/span><\/p>\n

Email:<\/strong> girotti@uthscsa.edu<\/span><\/p>\n

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Research Interests<\/b><\/p>\n\n\n\n\n\n
\u2022 interleukin 6<\/span><\/td>\n\u2022 JAK\/STAT3 pathway<\/span><\/td>\n<\/tr>\n
\u2022 stress<\/span><\/td>\n\u2022 HPA axis<\/span><\/td>\n<\/tr>\n
\u2022 mood disorders \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0<\/span><\/td>\n\u2022 cognitive flexibility<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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Research Activities<\/b><\/p>\n

I study the role of interleukin 6 (IL-6) and its downstream signaling pathway, the JAK\/STAT3 pathway, in normal brain function and in stress-induced psychopathology. IL-6 is involved in the peripheral inflammatory response to pathogens and initiates the fever response. However, it also functions as a growth and proliferation factor under normal, non-inflammatory conditions. IL-6 is not just produced by peripheral immune cells, but it is also present within the central nervous system, in glia (astrocytes and microglia) and in neurons; therefore this cytokine likely has CNS-specific functions, which are presently largely unknown.<\/span><\/p>\n

The hypothalamus is a brain area where IL-6 is particularly abundant and some evidence indicates that IL-6 is involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, the main stress response system of the body. One of my first questions after I joined the laboratory of Dr. D. Morilak at UTHSCSA, was to investigate the role of IL-6 and JAK\/STAT3 in HPA axis responses. In work funded by a NARSAD Young Investigator Award, I found that IL-6 and STAT3 modulate the way the HPA axis responds to different intensities and durations of stress (Girotti et al, 2011, 2013). Since abnormal responses of the HPA axis are observed in several psychopathologies that are exacerbated by chronic stress (such as depression, anxiety disorders and post-traumatic stress disorder), it is possible that hypothalamic IL-6 expression or its downstream signaling molecules, JAk2\/STAT3, are altered in these conditions.<\/span><\/p>\n

Besides their role in the hypothalamus, IL-6 and STAT3 have also an important role in facilitating cognitive function mediated by prefrontal cortex areas. During her thesis work, Jennifer Donegan, a former graduate student in the Morilak\u2019s lab, found that IL-6 and STAT3 signaling under non-inflammatory conditions are required for a rat to perform well in a task of cognitive flexibility, named \u201creversal learning\u201d, where the animal is required to shift attention from a previously rewarding contingency that has become non-rewarding to the now-rewarding contingency that was previously negative (Donegan et al 2014). An inability to adjust to new environmental contingencies and a lack of cognitive flexibility are hallmarks of several psychiatric disorders, including schizophrenia, obsessive-compulsive disorder, autism and depression. Therefore, Jennifer\u2019s data suggests that IL-6\/STAT3 dysregulation may contribute to cognitive dysfunction in these diseases.<\/span><\/p>\n

Previous work in the Morilak\u2019s laboratory showed that reversal learning is also dependent on intact serotonergic neurotransmission, specifically via 5HT2A receptors. Therefore, Jennifer and I postulated that one mechanism by which IL-6\/JAK\/STAT3 activation could mediate reversal learning was through an interaction with the 5HT2A receptor signaling pathway. We began to tackle this question in collaboration with Dr. Kelly Berg in the Department of Pharmacology, who provided us with a cultured neuronal cell line that expresses functional 5HT2A receptors and responds to IL-6 stimulation. In these experiments we found that indeed such cross-talk between the two pathways exists (Donegan et al 2015). These ideas form the basis of a recently funded R21.<\/span><\/p>\n

Some of the questions I am currently working on are:<\/span><\/p>\n

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  1. Is the interaction between IL-6\/JAK\/STAT3 pathway and serotonergic transmission in vivo necessary for cognitive flexibility?<\/span><\/li>\n
  2. Are other monoaminergic systems involved in IL-6\/STAT3 effects on cognitive flexibility?<\/span>
    \n<\/span> Noradrenergic transmission is also required for cognitive flexibility. With funds from a pilot project sponsored by the Center for Behavioral Neuroscience (CBN pilot grants) and in collaboration with Dr. Kelly Berg I will explore the possibility of an interaction between IL-6\/STAT3 signaling and the \u03b11 adrenergic receptor system in neuronal cell lines.<\/span><\/li>\n<\/ol>\n

    In future experiments, we will begin to identify the underlying circuitries, using viral-mediated cell-specific knock down of STAT3 expression or function to investigate whether STAT3 in a specific subpopulation of neurons is responsible for the behaviors.<\/span><\/p>\n

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    Accomplishments, Awards and Honors<\/b><\/p>\n