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MECHANISMS OF SEXUAL DIFFERENTIATION IN NEURAL SYSTEMS

Award Number: R01HD033044
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/12/2000
PERIOD OF PERFORMANCE END DATE: 05/31/2005

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MECHANISMS OF SEXUAL DIFFERENTIATION IN NEURAL SYSTEMS - DESCRIPTION (adapted from applicant's abstract): A large number of sex differences in the central nervous systems (CNS) of vertebrates have now been described. Such morphological dimorphisms may underlie well documented sex differences in behavior, in susceptibility to certain drugs, and in the incidence of some human mental disorders including autism, depression and schizophrenia. In many cases, neural sex differences have been shown to be due to differential exposure to gonadal steroid hormones in males and females. However, the cellular and molecular mechanisms governed by hormones in the nervous system are not well understood. The identification and cloning of several new neurotrophic molecules has fueled an explosion of research into the actions of trophic molecules in the CNS, and recent findings indicate a role for neurotrophic factors in sexually dimorphic development. Experiments in the first half of this proposal will test the idea that effects of gonadal steroids are mediated by trophic factors in a well-characterized model system. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles constitute an anatomically simple system that is sexually dimorphic in many mammals. SNB motoneurons reside in the lumbar spinal cord and innervate striated perineal muscles attached to the phallus. Androgens regulate SNB motoneuron survival during perinatal development, and SNB cell size in adulthood. Recent observations suggest that some effects of androgens on this system are mediated by protein neurotrophic factors. Trophic factor antagonists will be administered to developing and adult rats in order to identify endogenously produced factors controlling SNB cell survival and morphological plasticity. In the second half of this proposal, the intracellular events regulated by hormones and neurotrophic factors will be explored. Specifically, a role for the death-regulatory protein, Bcl-2, in sexually dimorphic cell death will be tested in the SNB and in the anteroventral periventricular nucleus (AVPV) of the hypothalamus. Because the neurotrophic factors and death-regulatory proteins to be examined are expressed throughout the nervous systems of many vertebrates, including humans, information gained from this work will be relevant to our overall understanding of the extracellular and intracellular molecules mediating hormone regulated development and plasticity in neural tissues.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $207,225 )
2004	2004	UNIVERSITY OF MASSACHUSETTS	406C-1 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Child Health and Human Development Extramural Research	000	10	5/12/2004	NON-COMPETING CONTINUATION	$207,225
														Subtotal = $207,225

Issue Date FY: 2003 ( Subtotal = $207,225 )
2003	2003	UNIVERSITY OF MASSACHUSETTS	406C-1 GOODELL BUILDING	AMHERST	MA	01003	HAMPSHIRE	USA	Child Health and Human Development Extramural Research	000	9		NON-COMPETING CONTINUATION	$207,225
														Subtotal = $207,225

Issue Date FY: 2002 ( Subtotal = $207,225 )
2002	2002	UNIVERSITY OF MASSACHUSETTS	406C-1 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Child Health and Human Development Extramural Research	000	8	6/17/2002	NON-COMPETING CONTINUATION	$207,225
														Subtotal = $207,225

Issue Date FY: 2001 ( Subtotal = $197,595 )
2001	2001	UNIVERSITY OF MASSACHUSETTS	406C-1 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Child Health and Human Development Extramural Research	000	7	5/30/2001	NON-COMPETING CONTINUATION	$197,595
														Subtotal = $197,595

Issue Date FY: 2000 ( Subtotal = $197,742 )
2000	2000	UNIVERSITY OF MASSACHUSETTS	406C-1 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Child Health and Human Development Extramural Research	000	6	6/12/2000	COMPETING CONTINUATION	$197,742
														Subtotal = $197,742

Grand Total All Awards = $1,017,012

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MECHANISMS OF SEXUAL DIFFERENTIATION IN NEURAL SYSTEMS

Award Number: R01HD033044

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/12/2000

PERIOD OF PERFORMANCE END DATE: 05/31/2005

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