Neuron density is decreased in the prefrontal cortex in Williams syndrome

Abstract

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99-112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Serotonergic innervation of the amygdala is increased in autism spectrum disorder and decreased in Williams syndrome

“…No correlations were found between age, sex, or postmortem interval and SERT-ir axon density. As observed in our previous analyses of the postmortem amygdala in WS and ASD [7,8], no significant differences in planimetric volume of any nucleus examined were found between the three groups. SERT-ir axon densities in the WS and NT infant subjects, although lower than the adult means, were within the standard deviation of the adults in their diagnostic group (Tables 2 and 3; Figs.…”

“…Here, we utilized immunohistochemical methods to determine the density of SERT immunoreactive (SERT-ir) axons in the lateral, basal, accessory basal, and central nuclei of the amygdala in WS and ASD, and we compared these results with our data on SERT-ir axon density in neurotypical (NT) postmortem brains, as previously reported in Lew et al [33], in order to test the hypothesis that serotonergic chemoarchitecture of targeted amygdaloid nuclei are disrupted in ASD and WS. Specifically, given previous qualitative observations of global increases in SERT axon density in ASD [34,35] and a pattern of opposing directions of change in WS and ASD cytoarchitecture [7,8,18], we predicted SERT axon density of the amygdala would be increased in ASD and decreased in WS compared to NT and that the basolateral nuclei would demonstrate the greatest differences between the two disorders.…”

“…In contrast, autism spectrum disorder (ASD) is a common neurodevelopmental disorder (1/59 in the USA [4]) with a highly complex and heterogeneous genetic etiology and a behavioral phenotype characterized in part by reduced drive for social engagement and decreased attention/atypical processing of the eyes of others, an important social stimulus in humans [5,6]. Our previous studies in the postmortem brains of individuals with ASD [7] and WS [8,9] have demonstrated opposing patterns of difference compared to healthy controls in the number of neurons in the same key social brain areas, paralleling differences in social behavior. Together, these findings suggest that a direct comparison of these two disorders may offer a unique human model in which to examine changes in the brain that may contribute to the biological underpinnings of social behavior and, furthermore, may help elucidate critical neural targets for potential therapeutics in disorders accompanied by sociobehavioral difficulties.…”

Early Life Adversity, but not suicide, is associated with less prefrontal cortex gray matter in adulthood

“…Our measured neuronal density was comparable to those reported in the literature (e.g., (Cotter et al, 2001;M. D. Underwood et al, 2012;Lew et al, 2017), but less than that reported by Rajkowska and colleagues who use a celloidin preparation producing considerable shrinkage and greater cell density (Rajkowska and Goldman-Rakic, 1995a) suggesting that our not finding a difference in neuron density was somehow a confound of the immunostaining or stereologic methods. We did detect a greater density of glial cell nuclei with ELA history and this difference is also not likely a confound since the glia density we measured was comparable to that reported in the literature (e.g., (Öngür et al, 1998;Cotter et al, 2001;J.…”

Altered Neocortical Dynamics in a Mouse Model of Williams–Beuren Syndrome

“…Abnormalities in the structure of the amygdala, hippocampus, and cerebral cortex have been described and related to the neurocognitive profile [2]. Anomalies in the cytoarchitecture of the cerebral cortex, specifically columnar orientation and cell and dendritic density, have been reported [3][4][5][6]. Sleep structure and efficiency have also been described as altered in WBS.…”