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

described FA S more than a doze n year s later. Kurtzman
and Mingo did not associate the craniofacial malformations
an d brai n dysfunctio n wit h prenata l
exposure t o alcohol, but the y di d link the diagnosti c
features that characterize FAS.
Ethanol can act through a number of mechanisms.
This is not to say that ethanol is a "dirty drug". Indeed,
evidence show s tha t i t affect s th e nervou s syste m i n
very specifi c ways . Moreover , th e manne r i n whic h
ethanol alter s developmen t instruct s u s abou t th e
adaptability an d resilienc y of the developin g nervous
system. Fro m a clinical perspective, a n understandin g
of the consequence s o f early exposure to ethanol i s of
paramount importance . Prenatal exposur e to alcoho l
affects upward s o f 1 % of al l liv e births an d i t i s th e
prime cause of mental retardation in the Unite d States
(Sokol e t al., 2003). Furthermore, ou r appreciatio n o f
ethanol-induced change s provide s a model o f and in -
sights int o th e etiolog y o f numerou s neurodevelop -
mental disorders, such as autism and schizophrenia.
The firs t se t of chapters i n Par t II addresses global
effects o f prenata l exposur e t o ethanol . Thes e in -
clude th e prevalenc e o f alcohol-induce d deficit s
among human s (Chapte r 8) , the structura l malfor -
mations cause d b y prenata l exposur e t o ethano l
(Chapter 9) , an d th e effect s o f ethanol o n nervous
system-endocrine system interactions (Chapte r 10) .
Following this discussio n i s a series of chapters tha t
focus o n th e fou r ontogeneti c phases : cell prolifera -
tion (Chapter s 1 1 and 12) , migration (Chapte r 13) ,
differentiation (Chapte r 14) , and death (Chapters 1 5
and 16) . The las t two chapters o f this section exam -
ine th e effect s o f ethano l o n tw o population s o f
neural-related cells : neura l cres t cell s (Chapte r 17 )
andglia (Chapter 18) .
NICOTINE-AFFECTED DEVELOPMENT
The fina l sectio n o f the boo k examines the respons e
of th e nervou s syste m t o a nicotin e challenge .
Whereas ethano l i s acte d upo n b y endogenou s
enzymes—for example , catalas e an d alcoho l
dehydrogenase —it does not act at a specific receptor .
In contrast , nicotin e allegedl y act s though a focused
endogenous mechanis m a t receptor s fo r cholinergic
neurotransmission. An understanding of the effect s of
nicotine i s not onl y importan t fo r appreciatio n o f a
basic scienc e issue , i t i s o f critica l clinica l impor -
tance. A fetus is exposed to nicotine though increase d
NEUROTOXICITY AND NORMAL DEVELOPMENT 5
blood concentrations in the pregnant woman as nicotine
freel y crosse s the placenta l "barrier," and infant s
are exposed to nicotine through secondhand smoke.
The clinica l problem o f fetal nicotin e exposur e is
discussed i n Chapter 19 . Nicotine i s a rather ubiquitous
substanc e — for thos e wh o smok e an d fo r thos e
who ar e expose d t o secondhand smoke . Nicotin e exposure
is often accompanied b y exposure to other substances
suc h a s alcohol . Thus , clinica l studie s hav e
fostered th e nee d t o conduc t well-controlle d anima l
studies to understand the behaviora l consequences of
exposure t o nicotin e pe r s e (Chapte r 20) . Althoug h
nicotine i s thought to act through specific cholinergic
receptors, it has broader effects through catecholaminergic
and othe r systems. These issues are examined i n
Chapters 2 1 and 22 , respectively. Chapter 2 3 explores
the effect s o f nicotine on specific ontogenetic events .
Separate studie s o f norma l developmen t an d o f
development altere d b y ethanol o r nicotin e provide
unique, thoug h limited , insigh t int o brai n develop -
ment. Eac h line of inquiry opens windows of understanding
tha t otherwis e migh t b e inaccessibl e fro m
other vantag e points . B y consolidating th e informa -
tion gathered from the three approaches, however, we
can gain a fuller appreciatio n (a ) of the complexit y of
neural development, an d (b ) of how i t can g o wrong
during a disease process.
Note
Abbreviations
CNS centra l nervous system
FAS feta l alcohol syndrome
1. I t wa s alleged that Harvey Kurtzma n an d Norman
Mingo were not th e first to dra w a face resemblin g
Alfred E . Neuman. Indeed , two lawsuits (base d on
copyrights file d i n 191 4 an d 1936 ) atteste d tha t
Kurtzman and Mingo were not the originators of the
caricature no w referre d t o a s Alfred E . Neuman. It
was used in advertisements for dental practices (see a
copy of the Manitoba Free Press in 192 8 [http://www
.imagehosting.us/index.php?action = show&ident =
728813]) and a n imag e was even used by the Nazi s
as part o f their anti-Semiti c campaig n i n th e 1930 s
(Djerassi, 1988 ; see http://garfield.library.upenn.edu/
essaysM2pl61yl989.pdf). [n.b. The nam e Alfred E .
Neuman an d th e imag e of the gap-toothe d person
were first joined i n 1956. ] The principa l (winning )
defense was that earlier artists had themselves copied