// NeighLab

Current Research Areas:

Reserach in the Neigh Lab broadly focuses on the mechanisms by which genetics and experience interact to modify the function of brain and its interactions with the other organ systems of the body.  Our work is highly integrative, multi-level, multi-disciplinary, and uses multiple model systems.

We are a question driven lab.  The techniques and approaches we use change to meet the demands of the next best scientific question.

We are a collaborative lab and research questions are chosen as a group.  

Currently, there are five general areas of research underway in the lab, but these divisions are fluid and responsive to the new information provided by the data that we generate, the innovative ideas of the research team, and the availability of funds to complete the work in the most rigorous manner possible.  

focus area #1: 

ADULT IMPLICATIONS OF CHRONIC ADOLESCENT STRESS: MEDIATORS AND MODIFIERS
Funding Source: National Institute of Nursing Research
NIH RePorter Link
Recent publications on this topic:
Bekhbat, M., Merrill, L., Lee, V., Neigh, G.N. (in press) Isoflurane differentially impacts the HPA axis in gene expression between male and female rats. Behavioural Brain Research.
Bourke, C., Glasper, E., Neigh, G (2014) SSRI or CRF antagonist partially ameliorate depressive-like behavior after adolescent social defeat. Behavioural Brain Research. 270:295-9.
Bourke, C.H., Raees, M.Q., Malviya, S., Bradburn, C.A., Binder, E.B., Neigh, G.N. (2013) Glucocorticoid sensitizers Bag1 and Ppid are regulated by adolescent stress in a sex-dependent manner. Psychoneuroendocrinology Jan 38(1): 84-93. PMID: 22647578
Bourke, C., Neigh, G.N. (2011) Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic. Hormones and Behavior, 60; 112-120.
Current research is building upon our previous findings to determine the extent to which interactions between FKBP5 and either the glucocorticoid receptor  or NFkB contribute to sex-specific effects of chronic adolescent stress.  In addition, we are examining using next generation sequencing techniques to identify the patterns of expression that are adopted by males and females following chronic adolescent stress in order to isolate candidate mechanisms for the prolonged changes in phenotype that are garnered by adolescent exposure to stressors. 

focus area #2: 

BIOLOGICAL MECHANISMS OF BIDIRECTIONAL RELATIONSHIP BETWEEN STRESS AND HIV
Funding Source: National Institute of Mental Health
NIH RePorter Link
Recent publications on this topic:
Neigh, G.N., Rhodes, S.T., Valdez, A., Jovanovic, T. (2015) PTSD co-morbid with HIV: separate but equal, or two parts of a whole? Neurobiology of Disease. Epub ahead of print.
 
Valdez, A., Rubin, L., Neigh, G.N. (in press) Untangling the Gordian knot of HIV, stress, and cognitive impairment. Neurobiology of Stress.
 
Rowson, A.S., Harrell, C.S., Bekhbat, M., Gangavelli, A., Wu, M.J., Kelly, S.D., Reddy, R., Neigh, G.N. (in press) Neuroinflammation and behavior in HIV-1 transgenic rats exposed to chronic adolescent stress. Frontiers in Psychiatry.
Nemeth, C.L., Bekhbat, M., Neigh, G.N. (2015) Neural effects of inflammation, cardiovascular disease, and HIV: parallel, perpendicular, or progressive? Neuroscience. 302: 165-173.
 
Panagiotakopoulos, L., Kelly, S., Neigh, G.N. (2015) HIV-1 proteins accelerate HPA axis habituation in female rats. Physiology and Behavior. 150:8-15.
Nemeth, C.L., Glasper, E.R., Harrell, C.S., Malviya, S., Otis, J.S., Neigh, G.N. (2014) Meloxicam blocks neuroinflammation, but not depressive-like behaviors, in HIV-1 transgenic female rats. PLos One. 9(10)e108399.
Current Research on this topic focuses on three areas:
1) The impact of chronic stress on pathogenesis and treatment response
2) The interactions between trauma and HIV and implications for PTSD and inflammation
3) The role of the glucocorticoid receptor in perpetuation of residual chronic inflammation in the context of HIV
This research area combines human investigation, nonhuman primate models, rodent models, and cell culture to develop convergining evidence regarding the biological mechanisms that drive the relationship between stress and HIV pathogenesis, treatment response, and co-morbidities.
RESEARCH PARTNERS FOR THESE PROJECTS INCLUDE:

focus area #3: 

GLUT 1 POLYMORPHISM DECREASES INCIDENCE OF DEPRESSION AND PTSD AFTER TRAUMA
Funding Source: National Institute of Mental Health
NIH RePorter Link
This research direction was born out of previous preclinical research aimed at understanding the role of a primary change in energetic availability in the generation of chronic stress-induced changes in behavior.  

Kelly, S.D., Harrell, C.S., Neigh, G.N. (2014) Chronic stress modulates regional cerebral glucose transporter expression in an age-specific and sexually-dimorphic manner. Physiology and Behavior. 126:39-49.

 

Harrell, C.S., Kelly, S.D., Neigh, G.N. (2014) Ovarian steroids influence cerebral glucose transporter expression in a region- and isoform-specific pattern. Journal of Neuroendocrinology. 26(4):217-25.

Harrell, C.S., Rowson, S., Neigh, G.N. (2015) Pharmacological stimulation of hypoxia inducible factor-1α facilitates the corticosterone response to a mild acute stressor. Neuroscience Letters. 600:75-9.

Subsequent work extended these questions into humans in collaboration with the Grady Trauma Project.  An abstract of this work can be found on pubmed until we complete the manuscript on this topic.  

focus area #4: 

EATING STRESS: IMPACT OF HIGH FRUCTOSE DIET DURING ADOLESCENCE
Recent publications on this topic:
Harrell, C.S., Burgado, J., Kelly, S.D., Johnson, Z.P., Neigh, G.N. (2015) High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats. Psychoneuroendocrinology. 62:525-264.
Harrell, C.S. Gillespie, C.F., Neigh, G.N. (2015) Energetic stress: The reciprocal relationship between energy availability and the stress response. Physiology and Behavior. Epub ahead of print.
We are currently developing new projects and funding applications in this area with the goal of building upon our current findings and further evaluate the basis of fructose-induced changes in behavior.  

focus area #5: 

NEUROVASCULAR IMPLICATIONS OF STRESS: CEREBROVASCULAR REMODELING AND CARDIOVASCULAR COMPROMISE
Recent publications in this area:

Neigh, G.N., Nemeth, C.L., Kelly, S.D., Hardy, E.E., Bourke, C., Stowe, Z.N., Owens, M.J. (in press) Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram. Physiology and Behavior.

 

Kalidindi, A., Kelly, S.D., Singleton, K., Guzman, D., Merrill, L., Willard, S.L., Shively, C.A., Neigh, G.N. (in press) Reduced vascularization of anterior hippocampus in a female monkey model of depression. Physiology and Behavior.

Nemeth, C.L., Miller, A.H., Tansey, M.G., Neigh, G.N. (2016) Inflammatory mechanisms contribute to microembolism-induced anxiety-like and depressive-like behaviors. Behavioural Brain Research. Epub ahead of print.

Nemeth, C.L., Neigh, G.N. (2015) Microemboli alter acute stress response and cause prolonged expression of MCP-1 in the hippocampus. Psychoneuroendocrinology. 54:71-77.

Nemeth C.L., Reddy, R., Behkbat, M., Bailey, J., Neigh, G.N. (2014) Microglial activation occurs in the absence of anxiety-like behavior following microembolic stroke in female, but not male, rats. Journal of Neuroinflammation. 11(1):174.

New projects are currently being developed in this area.  

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