Areas of Interest
The primary focus of the Seasholtz lab is studying the neural and endocrine control of the stress response. The mammalian stress response is mediated in large part by Corticotropin-Releasing Hormone (CRH, also known as CRF), a 41 amino acid peptide. In the neuroendocrine stress axis, hypothalamic CRH controls the release of adrenocorticotropin (ACTH) from the pituitary, which then controls glucocorticoid release from the adrenal gland. Within the brain, CRH acts as a neurotransmitter to control the behavioral, autonomic and immune responses to stress. Dysregulation of the CRH system has been linked to affective disorders including major depression, as well as anxiety disorders and addiction.
To understand the molecular regulation of the CRH system, particularly during stress, depression and relapse to addiction, the lab is studying the two classes of CRH receptors and the CRH-binding protein, using:
- Transgenic and knockout mouse models for behavioral analyses;
- In vivo stress and addiction studies;
- Cell culture analysis for biochemical signaling, trafficking and protein-protein interactions;
- In vitro assays with purified CRH-binding protein and CRH receptors for binding affinity determinations; and
- Molecular cloning for studies on the molecular evolution of CRH-binding protein (structure and function) from insects to humans.
Enhanced CRFR1-dependent regulation of a ventral tegmental area to prelimbic cortex projection establishes susceptibility to stress-induced cocaine seeking.
Vranjkovic O, Van Newenhizen E, Nordness ME, Blacktop JM, Urbanik LA, Mathy JC, McReynolds JR, Miller AM, Doncheck EM, Kloehn TM, Stinnett GS, Gerndt CH, Ketchesin KD, Baker DA, Seasholtz AF, Mantsch JR. J Neurosci. 2018; 38:10657-71.
Cell type-specific expression of corticotropin-releasing hormone-binding protein in GABAergic interneurons in the prefrontal Cortex.
Ketchesin KD, Huang NS, Seasholtz AF. Front Neuroanat. 2017; 11:90.
Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans.
Ketchesin KD, Stinnett GS, Seasholtz AF. Stress. 2017; 20:449-64.
For a complete list, visit https://www.ncbi.nlm.nih.gov/pubmed/?term=Seasholtz+AF%5BAuthor%5D