Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-4-14
pubmed:abstractText
Sex- and age-associated deficits in brain structure and behavior are reported in a number of neuropsychiatric disorders. Although genetic and environmental factors are thought to contribute to the pathogenesis, there are only few examples in clinical or experimental systems that have identified specific causes. Here, we report that transforming growth factor-alpha (TGFalpha) may regulate sex- and age-dependent development of forebrain structures and associated neural functions after puberty. Waved-1 (Wa-1) mice inherit an autosomal recessive, spontaneous mutation that results in a postnatal reduction in TGFalpha gene expression. The assessment of forebrain structures using a three-dimensional magnetic resonance microscopy indicated ventricular enlargement and striatal reduction in both male and female Wa-1 adult mice, with Wa-1 males exhibiting a more severe phenotype. In contrast, the hippocampal volume was reduced only in adult Wa-1 males. Similarly, behavioral analyses showed impaired auditory and contextual fear learning in adult Wa-1 males only, whereas abnormal stress response was expressed by both male and female adult Wa-1 mice. Interestingly, all behavioral deficits were absent before full sexual maturation, despite some slight forebrain structural abnormalities. These results suggest that TGFalpha may regulate postpubertal, sex differentiation in ventricular and periventricular anatomy and associated behavior, affecting predominantly males. In particular, the adult male-specific reduction in hippocampal volume may reflect an age- and sex-specific regulation of stress homeostasis and fear learning. Furthermore, a lack of a behavioral phenotype, despite anatomical alterations in peripubertal Wa-1 mice, suggests that analysis of certain neuroanatomical features at puberty may predict neurobehavioral deficits in adulthood.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3870-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15829639-Acoustic Stimulation, pubmed-meshheading:15829639-Age Factors, pubmed-meshheading:15829639-Aging, pubmed-meshheading:15829639-Animals, pubmed-meshheading:15829639-Animals, Newborn, pubmed-meshheading:15829639-Behavior, Animal, pubmed-meshheading:15829639-Brain, pubmed-meshheading:15829639-Catecholamines, pubmed-meshheading:15829639-Choice Behavior, pubmed-meshheading:15829639-Chromatography, High Pressure Liquid, pubmed-meshheading:15829639-Conditioning (Psychology), pubmed-meshheading:15829639-Corticosterone, pubmed-meshheading:15829639-Exploratory Behavior, pubmed-meshheading:15829639-Fear, pubmed-meshheading:15829639-Female, pubmed-meshheading:15829639-Fever, pubmed-meshheading:15829639-Gene Expression Regulation, Developmental, pubmed-meshheading:15829639-Imaging, Three-Dimensional, pubmed-meshheading:15829639-Magnetic Resonance Imaging, pubmed-meshheading:15829639-Male, pubmed-meshheading:15829639-Mice, pubmed-meshheading:15829639-Mice, Inbred C57BL, pubmed-meshheading:15829639-Mice, Neurologic Mutants, pubmed-meshheading:15829639-Prosencephalon, pubmed-meshheading:15829639-RNA, Messenger, pubmed-meshheading:15829639-Radioimmunoassay, pubmed-meshheading:15829639-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15829639-Sex Differentiation, pubmed-meshheading:15829639-Stress, Physiological, pubmed-meshheading:15829639-Transforming Growth Factor alpha
pubmed:year
2005
pubmed:articleTitle
Postpubertal sex differentiation of forebrain structures and functions depend on transforming growth factor-alpha.
pubmed:affiliation
Department of Neurobiology and Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. koshibu@hifo.unizh.ch
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural