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Postnatal Interventions to Attenuate the Effects of
Prenatal Alcohol Exposure:A Review of Animal Literature
Reuven Sussman, Hon BSc.,FAS Clinic Coordinator, Research Coordinator
Outline
• Background• 4 Modes of intervention:
– Environmental Enrichment– Postnatal Handling– Therapeutic Motor Training– Exercise
• Discussion• Future Directions
Background
• Early identification of at-risk children is becoming more accurate
• Early intervention reduces likelihood of secondary disabilities
• There is a lack of evidence-based interventions for FASD
• Animal studies offer advantages for the preliminary study of interventions
Background – FASD Characteristics
• Poor hand-eye coordination
• Tremors• Weak grip• Poor balance• Set shifting• Rely on
somatosensory information
• Hyperactivity
• Low IQ• Memory problems• Language problems• Attention problems• Slow reaction time• Visuospatial
abilities• Executive functioning
problems• Problems with
social/adaptive functioning
Background – FASD Brain
• Brain Structures– Prefrontal Cortex,
Corpus Callosum, Basal Ganglia
– Cerebellum– Hippocampus– Hypothalamic-
Pituitary-Adrenal (HPA) Axis
General Procedures
• Pregnant dams divided into 3 groups– Alcohol Exposed (AE), Pair-fed (PF), Food/water control
(C)
• Pups are kept with dam (or fostered) until weaning (21-28 days)
• Intervention applied– Environmental Enrichment (EE), Postnatal Handling (PH),
Therapeutic Motor Training (TMT), Exercise
• Behavioural and/or physiological testing– Water maze, Radial arm maze, avoidance learning,
conditioned taste aversion learning, open field activity– Analysis of neurons from certain brain regions, testing
stress hormone levels, stimulating/measuring LTP
General Procedures – con’t
Timing and Amount of Exposure
• Dose-response curve for maternal alcohol use is unknown in humans
• In rats, 200mg/dL for 4 hours causes massive neurodegeneration (but 83mg/dL throughout gestatation may be harmful)– Reviewed studies: avg ~150mg/dL, max
278mg/dL, min 100mg/dL
• Brain growth Spurt: human 3rd trimester, rat end of gestation to P14.
Environmental Enrichment (EE)
• Intervention: 8-12 animals, toys changed regularly
EE – con’t
• Behavioural effects:– EE rats ↑ water maze and radial arm
maze; but alcohol had no effect (2-3)– AE rats had hind limb ataxia; attenuated
by EE (3)– AE rats more active in open field (1,4)
and Y-maze (1), EE ameliorated over-activity in mice one of two studies (1,4)
– AE mice showed poor taste aversion learning; Attenuated by EE (5)
EE – con’t
• Neurological Effects:– Alcohol ↓ cortical thickness of occipital
lobe; EE not able to attenuate (trend toward ↑ brain weight) (2)
– AE-EE rats did not have ↑ dendritic spine density (6)
– Alcohol reduced survival of new hippocampal neurons; EE increased survival only in non-AE mice (7)
Postnatal Handling (PH)
• Intervention: Removal of dams/pups for 3 min or 15 min and putting them in separate cages– Handling is done pre-
weaning
PH –con’t
• Behavioural Effects:– Handling attenuated AE learning deficit
in step down avoidance task (8)– Weight gain deficits ameliorated (9-12)– Handling further worsens conditioned
taste aversion in AE rats (12)
PH – con’t
• HPA axis effects:– Handling, in combination with fostering
can improve regulation of HPA axis in some cases (9-11)
– AE rats have higher CRF mRNA levels; handling reduces levels in non-AE rats only (13)
Therapeutic Motor Training (TMT)
• Intervention: 10-20 days of obstacle course training
TMT – con’t
• Behavioural effects:– At end of training AE=PF=C on
course performance (14-15)– All rats tested on 3 novel tasks:
• AE rats performed worse on novel tests unless given TMT
• TMT attenuated performance deficits(15)
– Exercise group did not improve over controls (15)
• Neurological Effects:– AE rats had ↓ Purkinje Cells,
but rehabilitation ↑ parallel fibre synapses (16)
Exercise
• Intervention: Male rats housed individually with running wheel before testing
Exercise – con’t
• Behavioural effects:– AE rats performed worse on water maze;
voluntary exercise attenuated deficit (17)
• Neurological Effects:– AE rats have ↓ capacity for LTP; exercise
increases capacity (17)
Discussion
• EE may be actually be effect of isolation
• Rodent effects of prenatal alcohol different from humans
• Human exposure is more complex
Future Directions
• Research human interventions similar to EE, TMT, PH or exercise– What is handling?– What is Therapeutic Motor Training?– How early can interventions be applied?
Thank you
References• 1 Osborne et al (1980)• 2 Wainwright et al (1993)• 3 Hannigan et al (1993• 4 Mothes et al (1996), • 5 Opitz et al (1997)• 6 Berman et al (1996)• 7 Choi et al (2005)• 8 Gallo & Weinberg (1982)• 9 Weinberg et al (1995)• 10 Ogilvie & Rivier (1997)• 11 Gabriel et al (2000) • 12 Gabriel et al (2001)• 13 Gabriel et al (2005)• 14 Klintsova et al (1997)• 15 Klintsova et al (1998)• 16 Klintsova et al (2002)• 17 Christie et al (2005)
• If you require more detailed references please ask