Abstract/Details

The role of cell death in the development of a sexually dimorphic neuromuscular system


2007 2008

Other formats: Order a copy

Abstract (summary)

Hormonally regulated cell death is thought to underlie many sex differences in the nervous system, but little is known about the molecular mechanisms involved. This question was investigated in a sexually dimorphic neuromuscular system in mice. Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) innervate striated perineal muscles including the bulbocavernosus (BC) and levator ani (LA). In rats, SNB cell number and BC/LA muscle size are similar in males and females prenatally, but the postnatal persistence of this neuromuscular system is androgen dependent. Androgens reduce cell death of SNB motoneurons during a perinatal critical period and, as a result, males have more SNB motoneurons than do females in adulthood. The Bcl-2 family of proteins, which includes anti-apoptotic (e.g., Bcl-2) and pro-apoptotic (e.g., Bax, Bak) family members, regulates cell death in neurons and other tissues. I found that Bax is essential for the normal sex difference in SNB motoneuron number in adult mice. Experiments to characterize the time course of developmental cell death in the SNB of mice proved inconclusive based on counts of retrogradely-labeled SNB motoneurons and pyknotic cells in the SNB region, but suggest that developmental cell death may overlap with a period of late secondary SNB migration. Further, SNB motoneuron location differs between perinatal male and female mice.

It's controversial whether the sex difference in perineal muscle size is due to sexually dimorphic cell death or to androgen dependent growth, especially of the LA. We find that Bax deletion slightly increased LA fiber number in adult females, but did not eliminate the gross sex difference in perineal muscle size. Modest effects of Bax deletion on the perineal muscles in adulthood may result from functional redundancy between Bax and Bak. In confirmation, I found that Bax/Bak DKO females have a more than 10-fold increase in LA fiber number over that in wild type females. In addition, wild type females have a higher density of TUNEL-positive cells than do males in both the BC and the LA during perinatal life. Thus, cell death makes an important contribution to the sexually dimorphic development of the BC and the LA.

Indexing (details)


Subject
Neurology
Classification
0317: Neurology
Identifier / keyword
Biological sciences, Cell death, Neuromuscular, Sexually dimorphic, Spinal nucleus of the bulbocavernosus
Title
The role of cell death in the development of a sexually dimorphic neuromuscular system
Author
Jacob, Dena A.
Number of pages
121
Publication year
2007
Degree date
2008
School code
0118
Source
DAI-B 69/07, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549663881
Advisor
Forger, Nancy G.
University/institution
University of Massachusetts Amherst
Department
Neuroscience & Behavior
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3315510
ProQuest document ID
304838872
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304838872
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.