Altered Expression Levels of Neurodevelopmental Proteins in Fetal Brains of BTBR T+tf/J Mice with Autism-Like Behavioral Characteristics

Abstract

Autism is a brain developmental disorder with characteristics of social interaction defects, language and communication dysfunction, and repetitive behavior. Occurrence of autism is continuously increasing, but the cause of autism is not clearly defined. Genetic linkage or environmental factors were proposed as sources for pathogenesis of autism. BTBR T+tf/J (BTBR) mice were reported as an appropriate animal model for autism investigation because of their similarities in behavioral abnormalities with human autistic subjects. The aim of this study was to evaluate expression levels of proteins involved with brain development at fetal stage of BTBR mice. FVB/NJ mice were used as a control strain because of their social behaviors. Level of fetal brain immunoglobulin (Ig) G deposit was also evaluated. Fetal brains were obtained at d 18 of gestational period. Thirty-one and 27 fetuses were obtained from 3 pregnant BTBR and FVB dams, respectively. The level of glial fibrillary acidic protein expression was significantly lower in fetal brains of BTBR than FVB/NJ mice. Expression of brain-derived neurotrophic factor and myelin basic protein was significantly more upregulated in BTBR than in FVB/NJ mice. No significant difference was obtained for nerve growth factor between the two strains. Levels of IgG isotypes deposited in fetal brain of BTBR mice were significantly higher than in FVB mice except for IgG1. Overall, these results suggest that prenatal alterations in expression of various fetal brain proteins may be implicated in aberrant behavioral characteristics of BTBR mice.

Peripheral brain-derived neurotrophic factor in autism spectrum disorder: a systematic review and meta-analysis

“…Interestingly, we found that peripheral BDNF levels were higher in the ASD samples from childhood but not from adulthood. Evidence from animal models of ASD suggests that BDNF levels increase in the foetal brain 29 30 . In the ASD model of sodium valproate (VPA) exposure in utero, VPA administration has been shown to increase BDNF protein levels in the feotal mouse brain 5- to 6-fold in vitro and in vivo 29 .…”

The BTBR mouse model of idiopathic autism – Current view on mechanisms

“…No significant difference was obtained for NGF (nerve growth factor) between the two strains (Hwang et al 2015). The upregulation of BDNF expression at an early developmental stage (in stark contrast to the BDNF signaling deficiency in later life of BTBR mice) is in line with clinical data showing increased plasma BDNF in children with ASD (Wang M. et al 2015).…”

“…Abs were found to be elevated in the striatum and substantia nigra regions, while increased deposition of IgG 1 was found in the cerebellum, cortex, hippocampus and striatum (Kim et al 2016). Hwang and colleagues (Hwang et al 2015) looked at levels of IgG isotypes deposited in fetal brain of BTBR mice. All but IgG 1 were elevated in comparison to FVB fetal brains.…”

Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations

“…Inflammatory mediators profile, including levels of immunoglobulins (Ig)G in the fetal brain of BTBR mice, have been characterized. BTBR mice had lower levels of glial fibrillary acidic protein (GFAP), and higher levels of brain-reactive immunoglobulin (IgG), except IgG1, than FVB mice [ 33 ]. This is in contrast with reports in humans showing increased GFAP levels in children with ASD [ 34 ].…”