Navigation Links
Sex Steroid Regulation of Vasopressin Levels Secreted by hNT Neurons*

hNT Neurons used to imitate neurodegeneration


Rob D. Dickermana Thomas Fungweb N.Y. Zachariaha Walter J. McConathya,b
aDepartment of Medicine, bDepartment of Biomedical Sciences,
University of North Texas Health Science Center


This article describes an innovative technique that uses Stratagenes postmitotic human central nervious system cells (hNT Neurons) to imitate the aging human brain, neurodegeneration, and to investigate the role of sex steroids in neurotransmitter transcription and synthesis. Preliminary data show the potential of this model system.

The normal, physiological aging of the human brain has been associated with cellular atrophy and cell death. Sex differences in the aging brain have been documented by magnetic resonance imaging,1 suggesting that age-related changes in neuronal systems may be due in part to changes in the hormonal milieu. The age-related decline of circulating sex steroids is one of the most consistent findings in the aging literature.2,3 It has been demonstrated in the rat that vasopressinergic neurons are responsible for many of the behaviors and neurophysiological functions that are impaired in aging, including social memory, conditioned avoidance behavior and temperature regulation.4 A peptide hormone of interest, vasopressin, or antidiuretic hormone (ADH), is made in specialized neurons found in the hypothalamus and then transported to the pituitary gland. In neurons, both ADH content and ADH mRNA levels show a marked decline in senescence.5,6 Testosterone can reverse senescent decline in the levels of extrahypothalamic ADH mRNA in rats.7 In addition, the density of ADH nerve fibers is higher in male rats than in female rats.8 ADH nerve-fiber density can be reduced by castration and restored to normal density following testosterone replacement therapy.9

hNT Neurons and Alzheimers Disease

Another topic in neurogenerative research that could benefit from the hNT model system is Alzheimers disease. This disease is known to affect the female population more than the male population, and the females affected by Alzheimers disease suffer more severe forms of dementia.5 Dementia associated with Alzheimers disease is thought to be linked to the cholinergic system.6,7 Animal studies have demonstrated that the cholinergic system and overall brain activity can be enhanced by estrogen treatment.8,9 Recent studies have shown that estrogen stimulates mRNA for new growth of axons and dendrites and enhances gene expression for acetylcholine production.10,11 Several studies of menopausal women undergoing estrogen treatment demonstrate that estrogen directly affects memory.13-15 Interestingly, the male brain is thought to be less affected by Alzheimers due to the neural conversion of testosterone to estrogen by the enzyme aromatase.16 Thus, the normal hormonal milieu associated with aging may be directly responsible for age-related neurodegenerative changes and Alzheimers disease.

hNT Neurons and Sex Steroids

Steroid

Incubation Time
(hours)

Vasopressin
(pg/ml)

Control

6

1.8

24

3.6

48

6.3

Estrogen
(25 pg/ml)

6

3.6

24

3.6

48

6.3

Dihydrostestosterone

6

8.1

24

5.5

48

3.5

Testosterone
(3 ng/ml)

6

3.6

24

48

8.1

Testosterone
(9 ng/ml)

6

3.5

24

3.6

48

9.9

Testosterone
(18 ng/ml)

6

3.6

24

8.1

48

17.4

table 1

In order to demonstrate that sex steroids increase neuronal protein synthesis of the neuropeptide vasopressin, Stratagenes hNT Neurons were cultured with various physiological and supraphysiological levels of estrogen, testosterone and dihydrotestosterone (table 1). Cell culture media was collected at 6, 24 and 48 hours, and vasopressin was quantitated by radioimmunoassay (RIA). The more potent androgen, dihydrotestosterone, demonstrated the most immediate effect on vasopressin synthesis. High doses of testosterone had the greatest overall effect on vasopressin synthesis, while estrogen treatment mimicked control neurons. Neurons were also incubated with [35S]methionine and steroids to monitor sex steroid alterations in protein synthesis. Dihydrotestosterone appeared to be the most potent initiator of protein synthesis in the neurons.

These preliminary results demonstrate that hNT neurons synthesize the neuropeptide vasopressin. As previously demonstrated with animal models,2,5 hNT neuronal vasopressin synthesis responds to testosterone treatment. Incorporation of [35S]methionine indicates that hNT neurons appear to increase total neuronal protein synthesis in response to dihydrotestosterone.

Conclusions

Stratagenes hNT Neurons provide a viable model that may resemble the human aging brain more closely than previous animal models. Our results show that these neurons respond to various sex steroids and to varying concentrations of sex steroids. hNT neurons provide opportunities for research in the areas of steroid-responsive neuropeptides and age-related neurodegeneration.

Acknowledgments

The authors would like to thank the American Osteopathic Association and Glaxo-Wellcome for fellowship support.

REFERENCES

  1. Gur, R.C., et al. (1991) Proc. Natl. Acad. Sci. USA. 88: 2845-2849.

  2. Brenner, W.J., Vitiello, M.V., and Prinz, P.N. (1983) J. Clin. Endocrinol. Metab. 56: 1278-1287.

  3. Ravid, R., et al. (1987) Gerontology 33: 87-98.

  4. Dantzer, R., et al. (1988) Brain Res. 457: 143-147.

  5. Dorsa, D.M., and Bottemiller, L.A. (1982) Brain Res. 242: 3237-3242.

  6. Fliers, E., De Vries, G.J., and Swaab, D.F. (1985) Brain Res. 348: 1-8.

  7. Dobie, D.J., et al. (1992) Brain Res. 583: 247-252.

  8. Miller, M.A., Urban, J.H., and Dorsa, D.M. (1989) Endocrinology 125: 2335-2340.

  9. Devries, G.J., Duetz, W., and Buijs, R.M. (1984) Dev. Brain Res. 298: 141-145.

  10. Paganini-Hill, A., and Henderson, V.W. (1994) Am. J. Epidemiol. 140: 256-261.

  11. Rocca, W.A., et al. (1986) Ann. Neurol. 19: 415-424.

  12. Bartus, R.T., et al. (1982) Science 217: 408-414.

  13. Coyle, J.T., et al. (1983) Science 219: 1184-1190.

  14. Luine, V. (1985) Exp. Neurol. 89: 484-490.

  15. Luine, V., et al. (1980) Brain Res. 191: 273-277.

  16. Sohrabi, F., et al. (1994) J. Neurosci. 14: 459-471.


'"/>

Source:


Page: All 1 2 3 4 5 6 7

Related biology technology :

1. Reagents for Up and Down-Regulation of miRNA Activity in Mammalian Cells
2. Th1 and Th2 Balance, Regulation, and Involvement in Disease
3. Enzyme Immunoassay for Studying Intracellular Levels of cAMP
4. hNT BlueNeurons Express b-Galactosidase at High Levels
Post Your Comments:
*Name:
*Comment:
*Email:
TAG: Sex Steroid Regulation Vasopressin Levels Secreted hNT Neurons

(Date:8/19/2014)... A Geisinger researcher on a personal crusade ... for Disease Control and Prevention (CDC) award recognizing his ... Joseph Boscarino , Ph.D. MPH, senior ... of researchers nominated for the Centers for Disease Control ... Data Methods and Study Design. "Hepatitis C ...
(Date:8/19/2014)... 2014 Research and Markets  has announced the ... Global Strategic Business Report" report to their offering. ... Oxide Fuel Cells (SOFCs) in US$ Thousands. The report provides ... , Europe , Asia-Pacific ... provided for the period 2012 through 2020. Market data and ...
(Date:8/19/2014)... XenoTech announces an exclusive partnership ... production from bioactive small molecules. Based on ... enables convenient and timely assessment of critical metabolite ... President of Commercial Operations, Christian Darabant, “the value ... can be measured directly by comparison with the ...
(Date:8/19/2014)... 2014 CSSi, the leader in patient recruitment ... formation of the company,s Medical and Clinical Advisory Board ... Dr. William E. Gannon, Jr. to the ... The MCAB, with Dr. Gannon,s leadership, will ... and set strategic goals for the advancement and development ...
Breaking Biology Technology:Geisinger investigator nominated for federal award 2Geisinger investigator nominated for federal award 3Global Solid Oxide Fuel Cells (SOFCs) - Strategic Business Report 2014 2Beyond Metabolite Identification, Testable Quantities Now Offered by XenoTech 2Beyond Metabolite Identification, Testable Quantities Now Offered by XenoTech 3CSSi Appoints Dr. William E. Gannon, Jr. to Newly Formed Medical and Clinical Advisory Board 2CSSi Appoints Dr. William E. Gannon, Jr. to Newly Formed Medical and Clinical Advisory Board 3
... , ... Centage extends its financial performance management offerings to bring powerful, dynamic, driver-based planning, ... ... 2009 -- Centage Corporation, a leading provider of integrated budgeting, forecasting, consolidation and ...
... BOZEN, Italy, August 10 , ... Health Robotics today announced that it ... Robotics, CytoCare Robot. The,agreement enables McKesson to achieve its goal ... admixtures. , "We are very pleased ...
... LEXINGTON, Mass. and HEIDELBERG, Germany, Aug. 10 ... DNA-capture method, HybSelect(TM), to re-sequence the exons of genes involved ... the ultimate goal of developing genetic tests to detect carrier ... , In this collaboration the NCGR will bring ...
Cached Biology Technology:Centage Corporation Announces Planning Maestro Business Performance Management Software for Mid-Market Enterprises 2Centage Corporation Announces Planning Maestro Business Performance Management Software for Mid-Market Enterprises 3McKesson Expands Pharmacy Automation Product Portfolio to Include I.V. Therapy 2McKesson Expands Pharmacy Automation Product Portfolio to Include I.V. Therapy 3The National Center for Genome Resources Studies Childhood Diseases Using febit's DNA Capture Method 2The National Center for Genome Resources Studies Childhood Diseases Using febit's DNA Capture Method 3
(Date:8/20/2014)... Women who are poor experience higher cortisol levels in ... of the stress hormone, putting them at greater ... a new research from the University of Colorado Denver. ... American Journal of Human Biology , is the first ... to the socioeconomic status of their mothers during pregnancy. ...
(Date:8/20/2014)... When a colony of honeybees grows to about 4,000 ... reproductive cycle: the building of a special type of ... team of experts from the Department of Neurobiology and ... what starts the reproductive cycle of honeybee colonies. The ... The Science of Nature . , Reproduction isn,t ...
(Date:8/20/2014)... leaves, photosystem 1 (PS1) absorbs light and its ... carbon dioxide to biomass. Photovoltaic devices, mostly build ... but produce electricity. One approach for the development ... the semi-conductor with the isolated membrane protein complexes ... a highly stable PS1 from thermophilic cyanobacteria that ...
Breaking Biology News(10 mins):CU Denver researcher shows economic disparities impact infant health 2Worker bees 'know' when to invest in their reproductive future 2A semi-artificial leaf faster than 'natural' photosynthesis 2
... ) continues to expand at a record pace with the ... 2012, EOL provides data on nearly half of all described ... issues from the International Union for the Conservation of Nature ... before. In the four years since its first ...
... of species previously unknown to science have been discovered ... dark environment surrounding hydrothermal vents. The discoveries, made ... of Southampton and British Antarctic Survey, include new species ... an octopus. For the first time, researchers have ...
... Jan. 3, 2011 By manipulating the way bacteria ... have achieved an unprecedented degree of control over the ... potentially significant health and industrial applications, particularly to bioreactor ... Professor Thomas K. Wood and Associate Professor Arul Jayaraman ...
Cached Biology News:The Encyclopedia of Life expanding at a record pace 2'Lost world' discovered around Antarctic vents 2Manipulating way bacteria 'talk' could have practical applications, Texas A&M profs say 2Manipulating way bacteria 'talk' could have practical applications, Texas A&M profs say 3