Research experience
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Jan 2010–
Dec 2012Research: University of Hawaiʻi at Mānoa
University of Hawaiʻi at Mānoa · Pacific Biosciences Research CenterUSA · Honolulu -
Jan 2008
Research: Bucknell University
Bucknell UniversityUSA · Lewisburg
Publications (22) View all
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Article: Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles.
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ABSTRACT: Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder.Behavioural brain research 01/2013; · 3.22 Impact Factor -
Article: Addendum to 'BTBR T+tf/J mice: autism-relevant behaviors and reduced fractone-associated heparan sulfate' [Neurosci. Biobehav. Rev. 36(1) (2012) 285-296].
D Caroline Blanchard, Erwin B Defensor, Ksenia Z Meyza, Roger L H Pobbe, Brandon L Pearson, Valerie J Bolivar, Robert J BlanchardNeuroscience & Biobehavioral Reviews 11/2012; 36(10):2370. · 8.65 Impact Factor -
Article: The BTBR T(+)tf/J mouse model for autism spectrum disorders-in search of biomarkers.
Ksenia Z Meyza, Erwin B Defensor, Ashley L Jensen, Michael J Corley, Brandon L Pearson, Roger L H Pobbe, Valerie J Bolivar, D Caroline Blanchard, Robert J Blanchard[show abstract] [hide abstract]
ABSTRACT: Autism spectrum disorders (ASD) form a common group of neurodevelopmental disorders appearing to be under polygenic control, but also strongly influenced by multiple environmental factors. The brain mechanisms responsible for ASD are not understood and animal models paralleling related emotional and cognitive impairments may prove helpful in unraveling them. BTBR T(+)tf/J (BTBR) mice display behaviors consistent with the three diagnostic categories for ASD. They show impaired social interaction and communication as well as increased repetitive behaviors. This review covers much of the data available to date on BTBR behavior, neuroanatomy and physiology in search for candidate biomarkers, which could both serve as diagnostic tools and help to design effective treatments for the behavioral symptoms of ASD.Behavioural brain research 08/2012; · 3.22 Impact Factor -
Article: Absence of social conditioned place preference in BTBR T+tf/J mice: relevance for social motivation testing in rodent models of autism.
Brandon L Pearson, Jaclyn K Bettis, Ksenia Z Meyza, Lace Y Yamamoto, D Caroline Blanchard, Robert J Blanchard[show abstract] [hide abstract]
ABSTRACT: A major goal of translation research in autism is to characterize the physiological and psychological processes underlying behavioral abnormalities. Since autism reflects impairments in social motivation, we modified the mouse three-chamber social approach apparatus for use as a social conditioned place preference arena. We paired one of two unique contexts with social interactions in juvenile mice for five or ten conditioning sessions in BTBR T+tf/J mice and a control strain with normal approach behaviors (C57BL/6J) since the BTBR T+tf/J inbred mouse strain displays a variety of behavioral alterations analogous to symptoms of autism spectrum disorders. While C57BL/6J mice formed a conditioned place preference to the context associated with social interactions, particularly those receiving ten days of conditioning, BTBR T+tf/J mice did not. Neither absence of social proximity nor avoidance due to high rates of autogrooming appeared to underlie the impaired positive incentive value of the unconditioned social stimulus in the BTBR T+tf/J strain. These data contribute to a growing body of evidence suggesting that the BTBR T+tf/J strain shows impairments in all diagnostic domains of autism including social motivation. Additionally, social conditioning testing might provide an important social motivation measure in other rodent models of neuropsychiatric disorders characterized by social abnormalities.Behavioural brain research 04/2012; 233(1):99-104. · 3.22 Impact Factor -
Article: Oxytocin receptor and Mecp2(308/Y) knockout mice exhibit altered expression of autism-related social behaviors.
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ABSTRACT: The development of tasks measuring behaviors specific to the three major symptom categories for autism makes it possible to differentiate mouse models of autism spectrum disorders (ASD) in terms of changes in these specific categories. Prior studies indicate that BTBR T+tf/J mice, the strain that has been evaluated most extensively, show autism-relevant changes in all three symptom categories; reciprocal social interactions; communication; and repetitive, ritualized behaviors. This report reviews the behaviors of oxytocin receptor (Oxtr) and Mecp2(308/Y) wild-type (WT) and knockout (KO) mice, in a number of tests specifically designed to provide information on behaviors that may show functional parallels to the core symptoms of ASD. Oxtr KO mice show robust decreases in reciprocal social interactions, and reduced levels of communication, but no changes in repetitive, ritualized behaviors; whereas Mecp2(308/Y) KO mice show a slight but consistent enhancement of social behavior and communication, and no changes in repetitive, ritualized behaviors. This data base, although small, strongly indicates that mouse models can sort the diagnostic symptoms of autism, and suggests that biological and physiological analyses of these strains may be capable of providing differential information on the brain systems involved in particular symptoms of this disorder. Profiles of behavioral changes in other mouse models of ASD should provide additional specificity in the search for biomarkers associated with particular ASD symptoms and symptom clusters.Physiology & Behavior 03/2012; · 2.87 Impact Factor