Lawrence Reagan, PhD - US grants

DESCRIPTION (provided by applicant): This proposal will examine the relationship between diabetes-mediated impairments in insulin receptor (IR) signal transduction mechanisms, including insulin-stimulated protein phosphorylation and glucose transporter (GLUT) trafficking, and the development of cognitive deficits in diabetic subjects. The hippocampus is an important integration center for learning and memory in the mammalian central nervous system (CMS) and is particularly sensitive and responsive to changes in insulin concentrations. Insulin administration improves cognitive performance in a variety of physiological and pathophysiological settings, including diabetes. Conversely, decreases in IR expression and/or signaling may contribute to the development of diabetic encephalopathy, including cognitive deficits observed in type 1 subjects. Unlike the peripheral IR system, little is known about the functional role of IRs in the CMS and how the activity of the neuronal IR system may be impaired in diabetes phenotypes. In view of the emerging relationship between insulin and cognition and the importance of the hippocampus in cognition, the aims of this proposal are: 1) to establish the functional relationships of components of the IR system in the rat hippocampus, including phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (MARK) signaling and the insulin-sensitive GLUTs; 2) to determine whether the neurological consequences of diabetes include impairments in IR expression and/or signaling; 3) to determine whether downregulation of IR expression in the rat hippocampus produces impairments in IR/PI3-K/MAPK signaling and GLUT trafficking, thereby providing a mechanistic basis for decreases in behavioral performance observed in experimental models of type 1 diabetes. Successful completion of these studies will: 1) determine the signal transduction mechanisms of the IR system in the brain; 2) provide insight into the mechanisms through which insulin enhances cognitive function in physiological settings; 3) provide a fundamental mechanistic bridge between impairments in IR expression and/or signaling and the morphological, electrophysiological and cognitive deficits associated with type 1 diabetes.

The main goal of the Stress Neurobiology Workshop is to bring together researchers from all professional levels (undergraduate student to full professor) and from diverse disciplines to share and discuss recent findings toward understand the physiology associated with stress responses. Based on prior meetings, the Workshop will have a significantly broad attendance profile, attracting members from many fields and thereby facilitating multidisciplinary discussions related to stress research. The Workshop focuses on stress-related effects that integrate multiple systems, including physiology, immune, endocrine, and autonomic responses, as well as behavioral outcomes and resilience to stress-related disorders from a preclinical perspective. The meeting is focused on fundamental mechanisms through which organisms respond to stress in multiple species across the lifespan. This workshop, which takes place at the University of South Carolina in Columbia, SC, is the 6th of a biannual workshop series that offers the only small meeting focused on the neurobiology of stress that is open to students and PIs alike. This Workshop provides an opportunity for extensive face-to-face interactions among researchers and trainees with overlapping interests. The meeting also provides some historical perspective, introducing young investigators to the iconic researchers in stress neurobiology and their seminal work. More than half of the speakers are women at different career stages, from diverse cultural or ethnic backgrounds, and with different academic credentials. The research presented at this meeting will ultimately advance the understating of how stress affects brain and behavior and will also help train the next generation of scientists in this field.


In recent years there have been significant advances in understanding the neurobiology of stress, including the neuronal circuits, neurochemistry, and genetics that mediate stress responses and stress adaptation that will be the focus of our meeting. Many of these advances are supported by exciting new approaches to studying the brain and brain-body interactions such as optogenetics or chemogenetics, emerging conceptual understanding of brain-body communication via exosomes and the microbiome, as well as improvements in the analysis of large data sets, imaging and bioinformatics. This workshop focuses on stress susceptibility across the lifespan, highlighting different mechanisms contributing to resilience in stress responses from adolescence to senescence using different stress models and animal species. Additional sessions emphasize the range of structural, behavioral, genomic, and physiological processes associated with stress with sessions on the HPA axis, autonomic function, and synaptic plasticity. The scientific program includes two keynote lectures, five plenary sessions with five speakers each; two roundtable sessions, one of which is dedicated to harassment/discrimination-free scientific environment; two poster sessions (trainee presenters only); and a data blitz presentation for the travel award recipients (Graduate student and Postdoctoral fellows). A major goal of this this four-day workshop is to promote the professional development of trainees of all stages, new investigators, under-represented groups, and women. The requested funds will be used to support travel awards for trainees to attend the meeting. The vigorous scientific exchange at these meetings also generates new ideas and forges novel collaborations that support future advances.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.