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Research depicts studies using rodents with EEG electrodes/drug ports to measure
brain activity and behaviour, with studies based on extensive biochemical and tissue
culture research
Research ethics in strict accordance with Canadian Council on Animal Care and
University of Western Ontario Animal Use Committee
Genetic/environmental interaction
Where is the Lesion? What is the Lesion?
Genetic (instruction)
Environment
Insults:
Infection (virus)/inflammatory (IL-6)
toxins (alcohol)/metals/drugs(valproate)
(germ cell-fetus-neonate)
NRL AUT MG
MG RG
RG
RG MG
Autism- A Disorder of Energy Utilization and Toxin Elimination
Oxidative Stress:
Inflammation, impaired metabolism
Process similar to memory!!!
Antioxidants- glutathione
Facilitators of mitochondrial
function-carnitine, methylation-
Methyl B12 (accessibility to CNS?)
A mitochondrial disorder?
(Mitochondrial DNA mutations- risk)
Role of Vaccine MMR- Controversial
High association with Autism- over 40% difficult to examine and assess
Risk factors for seizure or movement disorder often similar for autism
Gather information from patients with surgical treatment of epilepsy and movement
disorder (deep brain electrographic changes)
Common mechanisms?
Epilepsy
Prolonged neuronal
discharge
humourlessness
Post-ictal psychosis
-hypergraphia
-number fixation
- preoccupation
hyperreligiousit with detail ?hyperinhibition
y
Temporal lobectomy for intractable seizure
Activated Microglia in Epilepsy
Appropriately sequencing
movement
Learned movements
Disorders of Movement:
Ticks, impulsive actions
and twirling
Repetitive Stereotypic
Movements in Autism
Enlarged Brain Size Systemic Changes
Increased Neuronal Density Immune System
Altered Cell Migration Gastrointestinal System
Seizure Disorder Metabolic Disorder
Detoxification Systems
Hormonal (glutathione)
Sex Hormones
Oxytocin
Vasopressin
AUTISM
Genetic Factors
Neurotransmitter
Growth Factors
Cell-cell Interaction
Environment
Sex Linked (Fragile X)
Metals
Hydrocarbons
White Matter Disorder Infectious
Glial/microglial Changes Drug (valproate)
Neuroinflammation Diet- Wheat
(Impaired Neurodevelopment and Casein Allergy
Cortico-cortical processing) Carbohydrate?
Autism- The Blind Men and the Elephant
ASDs
Psssst…
Dr. MacFabe
Feed Us and
Spread Us
Around!!
Vehicle
Baseline
* Treatment
6 9 *
+
4 6
2 3
0 0
Propanol PBS PBS
Low High Sodium Propanol
Low High Sodium
Propionate Propionate Acetate
Propionate Propionate Acetate
50
Turning
40
#
#
Legend
Mean Turning
30
10
7000
Distance Moved Number of Movements
500
SAL
6000 PPAH
400 SAL
*
4000 300
* * * *
3000
* *
200
*
2000 *
100
1000
0 0
BL T1 T2 T3 T4 T5 T6 T7 D8 BL T1 T2 T3 T4 T5 T6 T7 D8
Day Day
vehicle Propionate
PBS PPA
Diabetes Autism
Type 1 Type II
Can’t metabolize glucose Can’t metabolize SCFAs?
Multi- system involvement
Multiple Causes (Genes/diet/environment)
Present with Metabolic Crisis (i.e infection)
Treatment-Carbohydrate restriction (direct/indirect)
Treatment-Insulin/glyburide Carnitine/bacterial
eradication/probiotics/MB12?
Multi- system approach
Common Infections, Chronic Antibiotics, Clostridia and Carnitine=
Convulsions “The Perfect Storm”
Carnitine
Klaus-Peter Ossenkopp, Ph.D., Donald Peter Cain, Ph.D., Martin Kavaliers, Ph.D.,
(Department of Psychology (Neuroscience)- University of Western Ontario)
Fred Possmayer PhD. (Biochemistry, Obstetrics/Gynecology)
Lisa Tichenoff, Kelly Foley MSc., Roy Taylor, Francis Boon, Soelaha Shams ,Melissa
Gordon, Andrew Franklin MSc., Jennifer Hoffman MSc., Jennifer Martins MSc., Karina
Rodriguez-Capote, PhD, Yalda Mohammad-Asef
Heng Yong-Yi Ph.D and Leo Lau Ph.D (Surface Science Western- The University of
Western Ontario)