A postmortem stereological study of the amygdala in Williams syndrome
- 118 Downloads
Perturbations to the amygdala have been observed in neurological disorders characterized by abnormalities in social behavior, such as autism and schizophrenia. Here, we quantitatively examined the amygdala in the postmortem human brains of male and female individuals diagnosed with Williams Syndrome (WS), a neurodevelopmental disorder caused by a well-defined deletion of ~ 26 genes, and accompanied by a consistent behavioral profile that includes profound hypersociability. Using unbiased stereological sampling, we estimated nucleus volume, number of neurons, neuron density, and neuron soma area in four major amygdaloid nuclei- the lateral nucleus, basal nucleus, accessory basal nucleus, and central nucleus- in a sample of five adult and two infant WS brains and seven age-, sex- and hemisphere-matched typically developing control (TD) brains. Boundaries of the four nuclei examined were drawn on Nissl-stained coronal sections as four separate regions of interest for data collection. We found that the lateral nucleus contains significantly more neurons in WS compared to TD. WS and TD do not demonstrate significant differences in neuron number in the basal, accessory basal, or central nuclei, and there are no significant differences between WS and TD in nuclei volume, neuron density, and neuron soma area in any of the four nuclei. A similarly designed study reported a decrease in lateral nucleus neuron number in autism, mirroring the opposing extremes of the two disorders in the social domain. These results suggest that the number of neurons in the lateral nucleus may contribute to pathological disturbances in amygdala function and sociobehavioral phenotype.
KeywordsWilliams syndrome Neuropathology Neuroanatomy Neuron number Amygdala
This research was supported by the National Institutes of Health P01 NICHD033113, 5R03MH103697 and R56MH109587. We wish to thank the tissue donors and their families whose gift to science made this study possible, and especially Terry Monkaba and the Williams Syndrome Association. WS human tissue was obtained under the Ursula Bellugi WS Brain Collection, curated by KS at UC San Diego. Typically, developing human tissue was obtained from the University of Maryland Brain and Tissue Bank, which is a Brain and Tissue Repository of NIH NeuroBioBank. We thank Chelsea Brown, Valerie Judd, Hailee Orfant and Deion Cuevas for tissue processing assistance, and Kari Hanson, Branka Hrvoj, and Linnea Wilder for feedback.
Compliance with ethical standards
The authors declare they have no conflict of interest. This article does not contain any studies with human participants or authors performed by any of the authors. For this type of study formal consent is not required.
- Barger N, Stefanacci L, Schumann CM, Sherwood CC, Annese J, Allman JM, Buckwalter JA, Hof PR, Semendeferi K (2012) Neuronal populations in the basolateral nuclei of the amygdala are differentially increased in humans compared with apes: a stereological study. J Comp Neurol 520:3035–3054CrossRefPubMedPubMedCentralGoogle Scholar
- Edelmann L, Prosnitz A, Pardo S, Bhatt J, Cohen N, Lauriat T, Ouchanov L, Gonza-lez PJ, Manghi ER, Bondy P, Esquivel M, Monge S, Fallas M, Splendore A, Francke U, Burton BK, McInnes LA (2007) An atypical deletion of the Williams syndrome interval implicates genes associated with defective visuospatial processing and autism. J Med Genet 44:136–143CrossRefPubMedGoogle Scholar
- Meda SA, Pryweller JR, Thornton-Wells TA (2012) Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome. PLoS One 7Google Scholar
- Rubinow MJ, Mahajan G, May W, Overholser JC, Jurjus GJ, Dieter L, Herbst N, Steffens DC, Miguel-Hidalgo JJ, Rajkowska G, Stockmeier CA (2016) Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study. Brain Struct Funct 221(1):171–184CrossRefPubMedGoogle Scholar