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Published on: December 9, 2013
Postnatal apoptosis, development, and sex difference in the lateral septum of rats
Shinji Tsukahara1, Kouichi Inami, Fumihiko Maekawa
1Graduate School of Science and Technology, Kobe University, Nada-ku, Kobe 657-8501, Japan. stsuka@kobe-u.ac.jp
Insights
Apoptosis, or programmed cell death, shapes the developing rat lateral septum (LS). Sex differences in caspase-3-independent apoptosis contribute to the structural sexual differentiation of the intermediate lateral septum (LSi).
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- The lateral septum (LS) plays a crucial role in various behaviors.
- Understanding the developmental processes, including apoptosis, that contribute to its sexual differentiation is essential.
Purpose of the Study:
- To investigate the role of apoptosis in the structural and morphological sex differences of the LS during postnatal development.
- To examine the temporal and regional changes in apoptotic cell numbers and their correlation with LS development and sexual differentiation.
Main Methods:
- Immunohistochemical detection of apoptotic cells using antibodies against single-stranded DNA (ssDNA) and active caspase-3.
- Measurement of LS volume and the number of apoptotic cells in different LS subregions (dorsal, intermediate, ventral) at various postnatal days (PD1-31) in male and female rats.
Main Results:
- Apoptotic cell numbers in the LS peaked between PD6-8 and decreased thereafter, indicating developmental cell loss.
- Specific regional differences in apoptosis were observed, with higher caspase-3 activity in the ventral LS (LSv) early on.
- A sex difference in ssDNA-positive cells was noted in the intermediate LS (LSi) at PD16, with males showing higher numbers, but no corresponding caspase-3 difference.
- By PD31, the LSi was larger in females than in males, suggesting a role for apoptosis in this sexual dimorphism.
Conclusions:
- Apoptosis, partly mediated by caspase-3 activation, is a key process in the postnatal development of the rat LS.
- Regional variations in apoptosis occur within the LS during development.
- Caspase-3-independent apoptotic mechanisms contribute to the morphological sexual differentiation of the LSi.
Abstract:
To determine whether apoptosis is involved in the formation of the structure and morphological sex difference of the lateral septum (LS), the postnatal developmental changes in the number of apoptotic cells were examined in the LS on postnatal day 1 (PD1 = birth day), 4, 6, 8, 11, 16, and 31 in male and female rats. Apoptotic cells were immunohistochemically detected by antibody against single-stranded DNA (ssDNA) or active caspase-3. The volume of the LS was also measured and was found to increase with age. The number of apoptotic cells detected by anti-ssDNA in the LS increased from PD1 to PD8 but decreased after PD11. Also, the LS was divided into dorsal, intermediate, and ventral parts (LSd, LSi, and LSv), and the volume and number of ssDNA-immunoreactive cells in each part were measured on PD6, 8, 11, 16, and 31. In both sexes, a large number of ssDNA-immunoreactive cells was found in the LSd and LSi on PD8 (but not on PD6) and in the LSv on PD6 and PD8. On PD6, the number of active caspase-3-immunoreactive cells was significantly greater in the LSv than in the LSd or LSi, in both sexes. Only the LSi of males had a high number of ssDNA-immunoreacitve cells on PD16; the number was significantly greater than that of females of the same age. However, there was no significant sex difference in the number of active caspase-3-immunoreacitve cells in the LSi on PD16. On PD31, the volume of the LSi was significantly greater in females than in males. There was no sex difference in volume or number of apoptotic cells in the LSd or LSv. These findings indicate that loss of cells due to apoptosis, which is partially caused by activation of caspase-3, occurs in the LS during postnatal development, with regional differences. They also indicate that sex difference in caspase-3-independent apoptosis contributes to morphological sexual differentiation of the LSi.