This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, B. H. Articles by Gore, A. C. Search for Related Content PubMed PubMed Citation Articles by Miller, B. H. Articles by Gore, A. C.

N-Methyl-D-Aspartate Receptor Subunit Expression in GnRH Neurons Changes during Reproductive Senescence in the Female Rat

Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, and Brookdale Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029

Address all correspondence and requests for reprints to: Andrea C. Gore, Ph.D., Neurobiology of Aging Laboratories, Box 1639, Mount Sinai School of Medicine, New York, New York 10029. E-mail: andrea.gore{at}mssm.edu.

During reproductive senescence in females, the function of GnRH neurons becomes compromised, and this may play a role in the transition from normal estrous cycles to acyclicity. One hypothalamic component of this dysregulation is an alteration in the stimulatory effects of glutamate, acting via N-methyl-D-aspartate receptors (NMDARs), on GnRH release. The present study examined whether GnRH neurons express the subunits necessary to make functional NMDARs, and how subunit expression may change during aging in association with compromised reproductive physiology. Colocalization of the three NMDAR subunits that are most abundant in the hypothalamus (NR1, NR2A, or NR2B) with GnRH perikarya was determined in female rats at different stages of the reproductive life cycle: young (3–4 months) rats with regular estrous cycles, middle-aged (8–10 months) rats with regular estrous cycles, middle-aged rats with irregular estrous cycles, and middle-aged acyclic rats in persistent estrus. The number, percent, and localization of GnRH perikarya expressing NR1, NR2A, or NR2B were mapped and quantified by double label immunofluorescence microscopy. Overall, each of the NMDAR subunits was present in a majority of GnRH neurons. There were no age- or reproductive status-related changes in coexpression of NR1 or NR2A subunits in GnRH neurons. However, coexpression of the NR2B subunit, which affects several functional channel characteristics, was significantly lower in young compared with middle-aged rats, irrespective of reproductive status. This may result in an age-related increase in the ratio of the NR2B to the NR1 and NR2A subunits on GnRH neurons. These data indicate that the majority of GnRH neurons express the proteins needed to receive direct NMDAR-mediated glutamatergic input, and that a change in the stoichiometry of the NMDAR pentamer occurs during aging that precedes, and may have consequences for, altered neuroendocrine function.

This article has been cited by other articles:

				G. Neal-Perry, D. Lebesgue, M. Lederman, J. Shu, G. D. Zeevalk, and A. M. Etgen The Excitatory Peptide Kisspeptin Restores the Luteinizing Hormone Surge and Modulates Amino Acid Neurotransmission in the Medial Preoptic Area of Middle-Aged Rats Endocrinology, August 1, 2009; 150(8): 3699 - 3708. [Abstract] [Full Text] [PDF]

				G. S. Neal-Perry, G. D. Zeevalk, J. Shu, and A. M. Etgen Restoration of the Luteinizing Hormone Surge in Middle-Aged Female Rats by Altering the Balance of GABA and Glutamate Transmission in the Medial Preoptic Area Biol Reprod, November 1, 2008; 79(5): 878 - 888. [Abstract] [Full Text] [PDF]

				Y. Wang, M. Garro, H. A. Dantzler, J. A. Taylor, D. D. Kline, and M. C. Kuehl-Kovarik Age Affects Spontaneous Activity and Depolarizing Afterpotentials in Isolated Gonadotropin-Releasing Hormone Neurons Endocrinology, October 1, 2008; 149(10): 4938 - 4947. [Abstract] [Full Text] [PDF]

				W. Yin, J. M. Mendenhall, S. B. Bratton, T. Oung, W. G. M. Janssen, J. H. Morrison, and A. C. Gore Novel Localization of NMDA Receptors Within Neuroendocrine Gonadotropin-Releasing Hormone Terminals Experimental Biology and Medicine, May 1, 2007; 232(5): 662 - 673. [Abstract] [Full Text] [PDF]

				B. M. Nathan, C. A. Hodges, P. J. Supelak, L. C. Burrage, J. H. Nadeau, and M. R. Palmert A Quantitative Trait Locus on Chromosome 6 Regulates the Onset of Puberty in Mice Endocrinology, November 1, 2006; 147(11): 5132 - 5138. [Abstract] [Full Text] [PDF]

				J. H. Morrison, R. D. Brinton, P. J. Schmidt, and A. C. Gore Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women J. Neurosci., October 11, 2006; 26(41): 10332 - 10348. [Full Text] [PDF]

				P. L. Johnson and A. Shekhar Panic-prone state induced in rats with GABA dysfunction in the dorsomedial hypothalamus is mediated by NMDA receptors. J. Neurosci., June 28, 2006; 26(26): 7093 - 7104. [Abstract] [Full Text] [PDF]

				M. El-Etr, Y. Akwa, E.-E. Baulieu, and M. Schumacher The Neuroactive Steroid Pregnenolone Sulfate Stimulates the Release of Gonadotropin-Releasing Hormone from GT1-7 Hypothalamic Neurons, through N-Methyl-D-Aspartate Receptors Endocrinology, June 1, 2006; 147(6): 2737 - 2743. [Abstract] [Full Text] [PDF]

				W. Yin and A. C Gore Neuroendocrine control of reproductive aging: roles of GnRH neurons. Reproduction, March 1, 2006; 131(3): 403 - 414. [Abstract] [Full Text] [PDF]

				T. M. Plant, S. Ramaswamy, and M. J. DiPietro Repetitive Activation of Hypothalamic G Protein-Coupled Receptor 54 with Intravenous Pulses of Kisspeptin in the Juvenile Monkey (Macaca mulatta) Elicits a Sustained Train of Gonadotropin-Releasing Hormone Discharges Endocrinology, February 1, 2006; 147(2): 1007 - 1013. [Abstract] [Full Text] [PDF]

				G. S. Neal-Perry, G. D. Zeevalk, N. F. Santoro, and A. M. Etgen Attenuation of Preoptic Area Glutamate Release Correlates with Reduced Luteinizing Hormone Secretion in Middle-Aged Female Rats Endocrinology, October 1, 2005; 146(10): 4331 - 4339. [Abstract] [Full Text] [PDF]

				T. R. Chakraborty and A. C. Gore Aging-Related Changes in Ovarian Hormones, Their Receptors, and Neuroendocrine Function Experimental Biology and Medicine, November 1, 2004; 229(10): 977 - 987. [Abstract] [Full Text] [PDF]

				A. C. Gore, B. M. Windsor-Engnell, and E. Terasawa Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta) Endocrinology, October 1, 2004; 145(10): 4653 - 4659. [Abstract] [Full Text] [PDF]

				A. C. Gore Gonadotropin-Releasing Hormone Neurons: Multiple Inputs, Multiple Outputs Endocrinology, September 1, 2004; 145(9): 4016 - 4017. [Full Text] [PDF]