FETAL ALCOHOL SYNDROME (FAS) is the leading known cause of mental retardation and birth defects in the world. Fetal alcohol syndrome is a pattern of physical, behavioral and cognitive abnormalities seen in individuals exposed to alcohol in uterus. Because alcohol is a known teratogen and the damage done to a fetus by alcohol exposure is permanent, public education about the dangers of prenatal alcohol exposure has been extensive. Many of the features of the fetal alcohol syndrome are secondary to the effect of alcohol on brain development. These include microcephaly, short palpebral fissures, the long smooth philtrum and thin vermilion of the upper lip, joint anomalies, altered palmar crease pattern, and mental retardation. Animal studies as well as a limited amount of human data also show that maternal genotype is a key player : Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL), related to activity-dependent neuroprotective protein (ADNP), prevent alcohol-induced damage in a mouse model of FAS. In a recent study, the thyroxin reversed the deficit both in the level of their genes and their social behaviour, research is going on how the prenatal thyroid hormone supplementation reverses the behavioural deficits in the fetal alcohol spectrum disorder model. Another study used a priori approach to assess molecular phenotype in the cranial neural folds (head fold) of early mouse embryos soon after maternal alcohol treatment. FAS can be modulated pharmacologically with PK11195, a potent ligand with specific binding to the mitochondrial peripheral-type benzodiazepine receptor recognition site. PK11195 has been shown to protect early mouse embryos from eye and brain defects induced with diverse teratogens and to protect adult tissues from some inflammatory lesions. Microarray transcript profiling of the embryonic head fold at 3.0 hr after alcohol exposure or PK11195 counter-exposure enabled prioritization of candidate pathways that integrate the genomic response with genetic susceptibility of the system. These findings are consistent with the growing view that developmental exposure to alcohol alters common signalling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. CONCLUSIONS: Until the advent of effective prevention measures, it will remain necessary to seek ways to treat the life-long neurobehavioral consequences of prenatal alcohol exposure. Nevertheless, alcohol is a widely accepted and legal social drug, and many pregnant mothers continue to drink it while pregnant. Whereas, FAS is totally preventable by avoiding alco

1. FETAL ALCOHOL SYNDROME
BY
SHAIK SHAHEENA
VIGNAN’S UNIVERSITY
VADLAMUDI

2. When a woman drinks
alcohol during pregnancy,
she risks giving birth to a
child who will be born
with fetal alcohol
syndrome (FAS).

3. Alcohol travels through
this path and affects the
baby’s development,
particularly the heart and
the brain.
PATHWAY OF ALCOHOL FROM MOTHER TO FETUS

4. AN ARTICLE QUOTES THAT ‘
INDIAN FEMALES ARE
INCREASINGLY TURNING
EXPERIMENTAL’
THEIR RISING ASPIRATIONS
AND EXPOSURE TO DIFFERENT
LIFESTYLES APPEARS TO BE
DRIVING THIS DESIRE TO HAVE
NEWER EXPERINCES AND THAT
INCLUDES EXPERIMENTING
WITH ALCOHOL

8. Excessive alcohol exposure can cause
damage during all stages of
prenatal development.
• Pre-implantation: first 2 weeks
• Embryonic: 3-8 weeks after conception
• Fetal: from week 9 until birth

9. Alcohol can cause
permanent
damage to a baby
before most
women realize
they are
pregnant.

10. Fetal Alcohol Syndrome
(FAS)
which is characterized by
1. central nervous system
problems
2. low birth weight and
height
3. typical facial features
ALCOHOL RELATED BIRTH DEFECTS

11. • attention deficits
• language difficulties
• learning disabilities
• impulsive behavior
• poor judgment
CHILDREN WITH ALCOHOL RELATED BIRTH DEFECTS TYPICALLY
HAVE:

12. FETAL ALCOHOL SYNDROMECLEFT LIP/PALATE FAILURE
MIDLINE CLEAVAGE OF EMBRYONIC
FOREBRAIN
SINGULAR VENTRICULAR CAVITY

15. Similarities in mouse and human embryogenesis
provide opportunities to study the effects
of alcohol on development.
5 mm.
Mouse
(10 days old)
Human
(approx. 28 days old)
EYE
HEART
UPPER LIMB (ARM)
3 mm.

16. CELLS THAT SHOULD FORM MIDLINE STRUCTURES
OF THE BRAIN AND FACE ARE
KILLED BY ALCOHOL
Developing
brain and
face
Heart
Mouse embryo (viewed from
the front) at a stage corresponding
to a 22-23 day old human.
A close-up view of an alcohol-exposed
mouse embryo shows cells killed by alcohol
that have taken up a dark blue stain.

17. EYE EYE
A C
B D
MOUTH
MOUTH
NOSTRILS
NOSTRILS
MIDLINE STRUCTURES OF THE FACE AND BRAIN ARE DEFICIENT IN
ALCOHOL-EXPOSED MOUSE EMBRYOS AND IN INDIVIDUALS WITH FAS
THE FACE OF A CHILD
WITH FULL-BLOWN FAS
HAS FEATURES THAT
CAN BE CAUSED BY
DAMAGE TO MIDLINE
STUCTURES.
COMPARISON OF THE FACE (A) AND INTERIOR OF THE BRAIN (B) OF A NORMAL
MOUSE EMBRYO AND ONE DAMAGED BY ALCOHOL (C&D) SHOWS THAT THE NOSTRILS
ARE ABNORMALY POSITIONED (C) AND THE BRAIN IS MISSING MIDLINE STRUCTURES (D).

18. DIFFERENT APPROACHES FOR THE
DIAGNOSIS
TREATMENT
PRVENTION
OF ALCOHOL RELATED NEUROLOGICAL DISORDER
ESPECIALLY FETAL ALCOHOL SYNDROME
ARE DISCUSSED

19. • A variety of alcohol-induced alterations in maternal, placental and/or fetal
physiology have been proposed as the basis for this retarded fetal growth.
Using the embryonic chick as a model they have measured ethanol-induced
growth suppression as a function of embryonic age and ethanol dosage.
THE SUPPRESSION OF CELL DIVISION IS PROPORTIONAL TO THE ETHANOL
DOSE.
• Moreover, alcohol abuse can affect vitamin metabolism and absorption,
although how alcohol impairs such biochemical pathways remains to be
elucidated.
• For this purpose, we designed INTERACTOMES and employed
transcriptomic data analysis approaches to study the neural tissue of Mus
musculus exposed to ethanol prenatally and postnatally, simulating
conditions that could lead to FAS development at different life stages.
MOLECULAR MECHANISMS FOR GROWTH SUPPRESSION

20. This showed that FAS can promote early
changes in neurotransmitter release and
glutamate equilibrium, as well as an
abnormal calcium influx that can lead to
neuroinflammation and impaired
neurodifferentiation, both extensively
connected with vitamin action and
metabolism.
Genes related to retinoic acid, niacin,
vitamin D, and folate metabolism
were under expressed during
neurodevelopment and appear to
contribute to neuroinflammation
progression and impaired synapsis.

21. Alcohol increased embryonic and decidual
ADNP expression at 24 hours and it
persisted in the embryo for 10 days
Because ADNP is a neuro-protectant,
these findings suggest that it may be
released as a protective mechanism in FAS
Peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL),
related to activity dependent neuro-protective
protein (ADNP) prevent alcohol induced damage
in a mouse model of FAS

22. Advances in development of novel anti-oxidant therapies
as an approach for fetal alcohol syndrome prevention
Currently, there is no known effective strategy for prevention
(other than alcohol avoidance) or treatment.
The use of antioxidants as a potential therapeutic strategy for
the treatment using whole-embryo and culture cells models of
FASD was performed.
The induction of oxidative stress is believed to be one central
process linked to the development of the disease.
This experiment concluded that the imbalance of the
intracellular redox state contributes to the pathogenesis
observed in FASD models, and we suggest that antioxidant
therapy can be considered a new efficient strategy to mitigate
the effects of prenatal ethanol exposure.

23. A common molecular vulnerability in autism and
fetal alcohol spectrum disorder was found
Both disorders have symptoms of social
impairment and originate during brain
development in utero
A NORTHWESTERN MEDICINE STUDY

24. RAT MOTHER
( FED WITH ALCOHOL DURING PREGNANCY )
MALE OFFSPRING FEMALE OFFSPRING
SHOWED SOCIAL
IMPAIRMENT AND
ALTERED LEVELS
OF AUTISM-
RELATED GENES
FOUND IN HUMANS
WERE NOT
AFFECTED

26. This leads to apoptosis of the CRANIAL NEURAL CREST
CELLS (CNCCs) via two known mechanisms.
Ethanol can activate G-protein coupled receptors,
activating phospholipase C, which breaks down IP2 to IP3
and DAG.
IP3 mediated release of intracellular calcium stores leads to
increased Ca+2 dependent kinase activation.
Calmodulin and CamKII activation leads to
phosphorylation and proteolysis of β-catenin, which
affects gene expression and CNCC apoptosis.
Reducing β-catenin degradation is a potential
therapeutic target, and kinase inhibitors for CamKII and
GSK3β (canonical Wnt inhibitor) have been tested.
ETHANOL EXPOSURE CAN INDUCE THE CASPASE CASCADE
ETHANOL-INDUCED PRODUCTION OF CERAMIDE FROM
SPHINGOMYELIN is another potential mechanism that
leads to the malfunction of folbp-1, folate binding
protein-1, and contributing to FA deficiency.
This can lead to increased CNCC death.
Supplementation with FA can potentially rescue CNCC
death.
Dotted line indicates possible interaction between
canonical and noncanonical Wnt signaling pathways

27. INDIAN COUNTRY HAS LED RESPONSE TO THIS ISSUE BY
DEVELOPING THE MAJORITY OF PREVENTION AND
INTERVENTION CIRRCULA
THE NORTHWEST TRIBAL FASD PROJECT SEEKS TO REDUCE THE
INCIDENCE OF FASD AND TO ASSIST TRIBAL COMMUNITIES TO
IMPROVE THE QUALITY OF LIFE OF THOSE LIVING WITH FASD
WE MUST ALSO PROMOTE HOLISTIC HEALING THROUGH
TRADITIONAL AND DEVELOPMENTALLY APPROPRIATE
TECHNIQUES THAT ADDRESS THE PHYSICAL,
INTELLECTUAL, EMOTIONAL AND SPIRITUAL NEEDS OF
INDIVIDUALS AFFECTED BY FASD
STEPS TAKEN IN INDIA

28. CONCLUSIONS:
Until the advent of effective
prevention measures, it will remain
necessary to seek ways to treat the
life-long neurobehavioral
consequences of prenatal alcohol
exposure.

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