Brain Development: Normal Processes and the Effects of Alcohol ...

immune functio n i n th e offspring , wit h particula r
emphasis o n th e HP A axi s an d th e concep t o f feta l
programming. Ethanol-induce d disturbance s o f th e
reciprocal interconnections betwee n th e pregnant female
an d th e fetu s ma y provide a common pathway
by which perinatal exposure to different agent s results
in feta l programming . Th e feta l HP A axi s i s reprogrammed
by ethanol exposure such that HPA tone is
increased throughou t life . HP A activit y is increased
and HP A regulation i s altered unde r bot h basa l an d
stress conditions . Increase d exposur e t o endogenou s
glucocorticoids over the lifespa n ca n alte r behavioral
and physiological responsiveness and increase vulnerability
t o illnesse s late r i n life . Deficit s i n immun e
competence ma y b e on e o f th e long-ter m conse -
quences of fetal HP A programming. Prenatal ethanol
exposure compromise s offsprin g immun e functio n
and increases vulnerability to the immunosuppressive
effects o f stress.
It is now essential t o explore possible epigenomic
mechanisms mediatin g altere d physiologica l and be -
havioral functio n followin g prenata l ethano l expo -
sure. Th e fac t tha t ethano l cause s alteration s i n th e
methylation stat e withi n cell s support s the possibil -
ity tha t mechanism s simila r t o thos e describe d b y
Weaver an d colleague s (2004 ) mediat e th e change s
induced b y ethano l exposur e i n utero . Dat a fro m
such investigation s will have important implications
for th e developmen t o f therapeutic intervention s focused
o n reversin g the long-ter m advers e effect s o f
prenatal alcohol exposure .
Abbreviations
ACTH adrenocorticotropi c hormon e
ADX adrenalectom y
AVP arginin e vasopressin
J3-EP p-endorphi n
CBG corticosterone-bindin g globulin
CNS centra l nervous system
CON A concanavali n A
CORT corticosteron e
CRH corticotropin-releasin g hormone
CRH-R! corticotropin-releasin g hormone type 1
receptor
DO! l-(2 , 5-dimethoxy-4-iodophenyl)-2-amino -
propane hydrochloride
ETHANOL EFFECTS ON ENDOCRINE AND IMMUNE FUNCTION 17 3
8-OH-DPAT 8-hydroxy-2-(di-n-propylamino) -
tetralin
FASD feta l alcohol spectrum disorders
FEE feta l ethanol-exposed
S-HT serotoni n
G gestationa l day
GABA y-aminobutyri c acid
GDX gonadectom y
GnRH gonadotropin-releasin g hormone
GR glucocorticoi d receptor
hn heteronuclea r
HPA hypothalamic-pituitary-adrena l
HPG hypothalamic-pituitary-gonada l
Ig immunoglobuli n
IL interleuki n
LC-NE locu s coeruleu s noradrenergi c (sympa -
thetic adrenal medullary)
LPS lipopolysaccharid e
MHC majo r histocompatibility complex
MR mineralocorticoi d receptor
NE norepinephrin e
NMDA N-methyl-D-aspartat e
NO nitri c oxide
NOS nitri c oxide synthase
P postnata l day
POMC pro-opiomelanocorti n
PVN paraventricula r nucleus
PWM pokewee d mitogen
SHRP stres s hyporesponsive period
SIN-1 3-morpholinosydnonimin e
SNRP stres s nonresponsive period
TCR T cell receptors
TNF tumo r necrosis factor
ACKNOWLEDGMENTS Th e researc h from ou r laboratory
tha t i s reporte d in thi s revie w wa s supporte d by
grants fro m th e Nationa l Institut e o f Alcoho l Abus e
and Alcoholis m and fro m th e Universit y o f British Co -
lumbia Huma n Earl y Learnin g Partnershi p to J.W .
J.H.S. was supported by a Bluma Tischler postdoctoral
fellowship.