Progesterone blocks estrogen neuroprotection from kainate in middle-aged female rats.
The neuroprotective effects of estrogen in young adult rodents are well established. Less well understood is how estrogen neuroprotection is affected by aging and interactions with progesterone. In this study, we investigated the effects of estrogen and continuous progesterone, both alone and in combination, on hippocampal neuron survival following kainate lesion in 14-month-old female rats entering reproductive senescence. Our results show that ovariectomy-induced hormone depletion did not significantly affect the extent of kainate-induced neuron loss. Treatment of ovariectomized rats with estrogen significantly reduced neuron loss, however this effect was blocked by co-administration of continuous progesterone. Treatment of ovariectomized rats with progesterone alone did not significantly affect kainate toxicity. These results provide new insight into factors that regulate estrogen neuroprotection, which has important implications for hormone therapy in postmenopausal women.
Carroll
Jenna C
JC
Neuroscience Graduate Program, Davis School of Gerontology, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
Rosario
Emily R
ER
Pike
Christian J
CJ
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000473:pathology
D004967:Estrogens; D018696:Neuroprotective Agents; D011372:Progestins; D011374:Progesterone; D007608:Kainic Acid
Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H165-71
14988070
Neurobiol Aging. 2009 Jun;30(6):932-45
17950954
Exp Neurol. 1991 Nov;114(2):250-3
1748199
Brain Res. 2004 Oct 1;1022(1-2):148-56
15353224
Neurobiol Aging. 2001 Mar-Apr;22(2):309-19
11182481
J Neurotrauma. 2006 Jun;23(6):830-52
16774470
Exp Neurol. 2000 Sep;165(1):46-57
10964484
Neuroscience. 2006;138(3):1031-9
16310963
Seizure. 2008 Mar;17(2):176-80
18187348
Exp Neurol. 2003 Jul;182(1):124-34
12821382
Biol Reprod. 1988 May;38(4):780-9
3401536
Best Pract Res Clin Endocrinol Metab. 2003 Mar;17(1):105-22
12763515
Front Neuroendocrinol. 2008 Jan;29(1):88-113
17980408
Endocrinology. 2006 Jan;147(1):607-14
16239296
Brain Res. 2006 Jul 12;1099(1):206-10
16793026
Neuroreport. 2004 Dec 3;15(17):2659-63
15570173
J Neurosurg. 1997 Nov;87(5):724-30
9347981
J Cereb Blood Flow Metab. 1998 Nov;18(11):1253-8
9809515
Trends Endocrinol Metab. 2002 Aug;13(6):229-30
12128278
Biol Reprod. 1981 May;24(4):784-94
7195743
Brain Res. 2002 Jul 5;943(1):151-61
12088849
Environ Health Perspect. 1995 Oct;103 Suppl 7:5-8
8593874
Pharmacol Ther. 2007 Oct;116(1):77-106
17659348
Neuroscience. 2003;122(3):573-8
14622899
Neurobiol Aging. 2003 Sep;24(5):733-43
12885581
Neuroscience. 2006;138(3):831-5
16310320
Novartis Found Symp. 2000;230:94-107; discussion 107-11
10965504
Stroke. 2000 Jan;31(1):161-8
10625733
Neurosci Lett. 1995 Mar 24;188(2):117-20
7792054
Eur J Neurosci. 2006 Jul;24(1):229-42
16882019
J Neurosci. 2007 Nov 28;27(48):13357-65
18045930