Estrous cycle regulates activation of hippocampal Akt, LIM kinase, and neurotrophin receptors in C57BL/6 mice.
Estradiol modulates dendritic spine morphology and synaptic protein expression in the rodent hippocampus, as well as hippocampal-dependent learning and memory. In the rat, these effects may be mediated through nongenomic steroid signaling such as estradiol activation of the Akt and LIM kinase (LIMK) pathways, in addition to genomic signaling involving estradiol upregulation of brain-derived neurotrophic factor expression (BDNF). Due to the many species differences between mice and rats, including differences in the hippocampal response to estradiol, it is unclear whether estradiol modulates these pathways in the mouse hippocampus. Therefore, we investigated whether endogenous fluctuations of gonadal steroids modulate hippocampal activation of the Akt, LIMK, and the BDNF receptor TrkB in conjunction with spatial memory in female C57BL/6 mice. We found that Akt, LIMK, and TrkB were activated throughout the dorsal hippocampal formation during the high-estradiol phase, proestrus. Cycle phase also modulated expression of the pre- and post-synaptic markers synaptophysin and post-synaptic density 95. However, cycle phase did not influence performance on an object placement test of spatial memory, although this task is known to be sensitive to the complete absence of ovarian hormones. The findings suggest that endogenous estradiol and progesterone produced by the ovaries modulate specific signaling pathways governing actin remodeling, cell excitability, and synapse formation.
Spencer
J L
JL
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA. spencej@rockfeller.edu
Waters
E M
EM
Milner
T A
TA
McEwen
B S
BS
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000076122:Disks Large Homolog 4 Protein; D004958:Estradiol / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D054461:Lim Kinases / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017475:Receptors, Nerve Growth Factor; D016708:Synaptophysin; D011374:Progesterone; D004958:Estradiol; D054461:Lim Kinases; D051058:Oncogene Protein v-akt; D051528:Guanylate Kinases