Development and Aging Expression of Cystathionine-Beta Synthase in the Temporal Lobe and Cerebellum of Down Syndrome Patients

Abstract

Down’s syndrome (DS) is characterized by intellectual disabilities and Alzheimer-type dementia. Cystathionine-β synthase (CBS) plays a role in the production of hydrogen sulfide (H2S) in the brain and is encoded by a gene which is localized in the DS critical region of chromosome 21. The expression of CBS was compared during development and aging. Therefore, cerebri (temporal lobe) and cerebelli from fetuses and adults were studied in 22 normal controls and 21 DS patients using immunohistochemical methods. During normal development, CBS-positive astrocytes appeared in the cortical layer at 14 weeks of gestation (GW), remained elevated until 34 GW and decreased slightly during the infantile period (1–11 months of age). A few CBS-positive neurons were transiently found in the deep cortical layer only at 35 GW. In the cerebellum, CBS-positive Bergmann glial cells were found from 26 GW to adulthood in both controls and DS patients. In DS, there were greater numbers of CBS-positive astrocytes, situated predominantly in granular cell layers II and IV, compared to the controls. In addition, CBS-positive astrocytes were also increased around senile plaques in adults with DS. The high level of CBS in the granular cell layers in DS may be related to an abnormal development of inhibitory neurons and may be responsible for the pathogenesis of intellectual disability, while the increased CBS observed in adult DS may be related to the pathogenesis of Alzheimer-type dementia.