A working hypothesis June 25 2014 Sneha Sheth Experimental Medicine UBC Supervisor Dr Chris Shaw Research Question Do aluminum adjuvants contribute to an autismlike phenotype in young mice ID: 525414
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Slide1
Aluminum and Autism Spectrum Disorders: A working hypothesis
June 25, 2014
Sneha
Sheth
Experimental Medicine, UBC
Supervisor: Dr. Chris ShawSlide2
Research Question: Do aluminum adjuvants contribute to an autism-like phenotype in young mice? Slide3
Autism Spectrum Disorders (ASD)Slide4
Two-Hit hypothesis for ASD
Genes
Environment
Neuroinflammatory
processes and immune dysfunction associated with
ASD
can result
following pre or post natal
exposure to various
xenobiotics (i.e., bisphenol A, PCBs, Pb, Hg and Al)4Slide5
Examples of Aluminum ExposureSlide6
Aluminum
is a neurotoxin
impairs memory, cognition and psychomotor control
impairs neurotransmission and synaptic activity
blood brain barrier changes
pro-oxidant
activates microglia and brain inflammation
depresses brain glucose metabolism
impairs protein transcription
promotes
neurite
damage
promotes amyloidosis
(
Tomljenovic
, J of
Alzheimers
Dis
2011, 23(4):
567-598
)Slide7Slide8
A case for Al in the etiology of ASD?Slide9Slide10Slide11
Social Interaction Test
Protocol
:
Yang, M., Silverman, J. L. and Crawley, J. N. 2011. Automated Three-Chambered Social Approach Task for Mice. Current Protocols in Neuroscience. 56:8.26.1–8.26.16.Slide12
Study DesignSlide13
Preliminary
data
*
Males
FemalesSlide14
Overall Limitations & proposed solutionsSlide15
Conclusion and key takeaways
Aluminum is a proven neurotoxin
Oddities in social interaction is a defining characteristic of Autism Spectrum disorders
Young male and female mice have shown deficits in social interaction as a result of aluminum exposure
More data is needed to establish a putative role of aluminum in the etiology of Autism Spectrum DisordersSlide16
References
Hendry J,
DeVito
T,
Gelman
N,
Densmore
M,
Rajakumar
N, Pavlosky W, Williamson PC, Thompson PM, Drost DJ, Nicolson R.White matter abnormalities in autism detected through transverse relaxation time imaging. Neuroimage 2006; 29: 1049–57Vargas DL, Nascimbene
C, Krishnan C, Zimmerman AW,
Pardo
CA.
Neuroglial
activation and
neuroinflammation
in the brain of patients with autism. Ann Neurol. 2005;57(1):67-81.
Vojdani
A, Campbell AW,
Anyanwu
E, et al. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with
encephalitogenic
proteins from milk, Chlamydia
pneumoniae
and Streptococcus group A. J Neuroimmunol2002;129(1-2):168-77
Dietert
RR,
Dietert
JM. Potential for early-life immune insult including developmental
immunotoxicity
in autism and autism spectrum disorders: focus on critical windows of immune vulnerability. J
Toxicol
Environ Health B
Crit
Rev. 2008;11(8):660-80.
Tomljenovic L. Aluminum and Alzheimer's Disease: After a Century of Controversy, Is there a Plausible Link? J
Alzheimers Dis. 2011;23(4):567-98.Toimela
T,
Tahti
H. Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and
methylmercury
in cell lines of neural origin. Arch
Toxicol
. 2004;78(10):565-74.
Li X,
Zheng
H, Zhang Z, Li M, Huang Z,
Schluesener
HJ, et al.
Glia
activation induced by peripheral administration of aluminum oxide
nanoparticles
in rat brains.
Nanomedicine
. 2009;5(4):473-9
W.
Zheng
, Journal of Toxicology. Clinical Toxicology 39 (2001) 711–719.
Oliveira, G.,
Diogo
, L.,
Grazina
, M., Garcia, P., Psych, A. A., Marques, C., Miguel, T., Borges, L., Vicente, A. M. and Oliveira, C. R. (2005), Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Developmental Medicine & Child Neurology, 47: 185–189.
Tomljenovic
,
Lucija
; Shaw, Christopher A(2011)
Journal of inorganic biochemistry
vol. 105 (11) p. 1489-99
C.J.
Newschaffer
, M.D.
Falb
, J.G. Gurney, Pediatrics 115 (2005) e277–e282.Slide17
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