We will continue our study of the role of steroid hormones, specifically androgens such as testosterone, in the development and adult function of spinal cord regions controlling masculine copulatory behaviors. By studying a simplified model system, the spinal nucleus of the bulbocavernosus (SNB), which consists of lumbar motoneurons innervating the striated perineal muscles called bulbocavernosus (BC), we can ask fundamental questions about the role of steroid hormones in sculpting the developing nervous system and fine-tuning the adult nervous system to control behavior, especially reproductive behaviors. We will use Cre- lox- technologies in laboratory mice to selectively disable the genes for the androgen receptor (AR) and/or brain-derived neurotrophic factor (BDNF). By disabling such genes in either motoneurons or striated muscle fibers we can ask the site of androgen action for maintaining the system during perinatal development, and for regulating the somata and dendrites of the SNB motoneurons in adulthood, as well as the behavioral capacity of the system. These studies of steroidal regulation of the SNB system may prove relevant to human disorders such as amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (SBMA) and Shy Drager disease. A characteristic of each of these human disorders is that BC motoneurons are either selectively spared or selectively targeted compared to other motoneurons. Discovering how BC motoneurons are regulated by androgen may reveal why they are selectively vulnerable in human neuromuscular disorders.

Public Health Relevance

We will continue our study of the role of steroid hormones, specifically androgens such as testosterone, in the development and adult function of spinal cord regions controlling behavior. Studying this steroid- sensitive system may afford a better understanding of human disorders such as amyotrophic lateral sclerosis, and spinal bulbar muscular atrophy, in which such steroid-sensitive motoneurons are selectively spared.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS028421-21
Application #
8625832
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Gubitz, Amelie
Project Start
1990-04-01
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
21
Fiscal Year
2014
Total Cost
$317,796
Indirect Cost
$101,233
Name
Michigan State University
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Chen, Chieh V; Brummet, Jennifer L; Lonstein, Joseph S et al. (2014) New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice. Horm Behav 65:211-8
Renier, Kayla J; Troxell-Smith, Sandra M; Johansen, Jamie A et al. (2014) Antiandrogen flutamide protects male mice from androgen-dependent toxicity in three models of spinal bulbar muscular atrophy. Endocrinology 155:2624-34
Johnson, Ryan T; Breedlove, S Marc; Jordan, Cynthia L (2013) Androgen receptors mediate masculinization of astrocytes in the rat posterodorsal medial amygdala during puberty. J Comp Neurol 521:2298-309
Zuloaga, Damian G; Poort, Jessica E; Jordan, Cynthia L et al. (2011) Male rats with the testicular feminization mutation of the androgen receptor display elevated anxiety-related behavior and corticosterone response to mild stress. Horm Behav 60:380-8
Zuloaga, Damian G; Jordan, Cynthia L; Breedlove, S Marc (2011) The organizational role of testicular hormones and the androgen receptor in anxiety-related behaviors and sensorimotor gating in rats. Endocrinology 152:1572-81
Ottem, Erich N; Poort, Jessica E; Wang, Hongbing et al. (2010) Differential expression and regulation of brain-derived neurotrophic factor (BDNF) mRNA isoforms in androgen-sensitive motoneurons of the rat lumbar spinal cord. Mol Cell Endocrinol 328:40-6
Johnson, Ryan T; Breedlove, S Marc (2010) Human trust: testosterone raises suspicion. Proc Natl Acad Sci U S A 107:11149-50
Pappas, Samuel S; Tiernan, Chelsea T; Behrouz, Bahareh et al. (2010) Neonatal androgen-dependent sex differences in lumbar spinal cord dopamine concentrations and the number of A11 diencephalospinal dopamine neurons. J Comp Neurol 518:2423-36
Johnson, Ryan T; Breedlove, S Marc; Jordan, Cynthia L (2010) Astrocytes in the amygdala. Vitam Horm 82:23-45
Martel, Michelle M; Klump, Kelly; Nigg, Joel T et al. (2009) Potential hormonal mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A new perspective. Horm Behav 55:465-79

Showing the most recent 10 out of 47 publications