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The Journal of Neuroscience, July 15, 1999, 19(14):5792-5801
Estrogen Stimulates a Transient Increase in the Number of New
Neurons in the Dentate Gyrus of the Adult Female Rat
Patima
Tanapat,
Nicholas B.
Hastings,
Alison J.
Reeves, and
Elizabeth
Gould
Department of Psychology, Princeton University, Princeton, New
Jersey 08544
To determine whether a sex difference exists in the production of
hippocampal cells during adulthood, we examined proliferating cells and
their progeny in adult rats using the thymidine analog bromodeoxyuridine (BrdU) combined with immunohistochemistry for markers
of neurons and glia. Additionally, to determine whether ovarian
hormones affect cell proliferation, we examined the numbers of
BrdU-labeled cells at different estrous cycle stages and after ovarian
steroid manipulation. Stereological analyses of the numbers of
BrdU-labeled cells revealed that females produced more cells than males
in the dentate gyrus but not in the subventricular zone. The production
of new hippocampal cells in females appears to be affected by ovarian
hormone levels; ovariectomy diminished the number of BrdU-labeled
cells, an effect reversed by estrogen replacement. A natural
fluctuation in cell proliferation was also noted; females produced more
cells during proestrus (when estrogen levels are highest) compared with
estrus and diestrus. Many of these cells acquired neuronal
characteristics, including the formation of dendrites and expression of
Turned-On-After-Division 64 kDa, a marker of immature granule neurons,
and the calcium-binding protein calbindin, a marker of mature granule
neurons. However, examination of the numbers of pyknotic cells and the
numbers of BrdU-labeled cells at longer survival times revealed that
many new cells in the dentate gyrus eventually degenerate. Consistently the number of labeled cells in females is no longer higher than that
observed in males by 2 weeks after the last BrdU injection. These
findings suggest that estrogen-enhanced cell proliferation during
proestrus results in more immature neurons in the hippocampal formation
of females compared with males and present the possibility that these
new cells exert an important influence on hippocampal function.
Key words:
neurogenesis; dentate gyrus; granule neuron; sex
differences; estrous cycle; estrogen
Copyright © 1999 Society for Neuroscience 0270-6474/99/19145792-10$05.00/0
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