Altered Cholinergic Function in the Basal Forebrain of Girls with Rett Syndrome

Rett syndrome (RS) is a neurodevelopmental disorder that is predominant in females and is associated with cortical atrophy, stereotyped hand movements and severe mental deficiency. Previous studies have demonstrated a significant decline in number of choline acetyltransferase (ChAT)-containing neurons throughout the forebrain of RS girls. The loss of these ChAT-positive cells may be caused by a lack of nerve growth factor (NGF). In the current study, cortical levels of NGF were normal in RS girls as compared to age- and sex-matched controls. The number of neurons within the basal forebrain that express the 75 kDa (p75) low-affinity receptor for NGF was unchanged. In contrast, the number of ChAT-positive neurons was significantly decreased. The results suggest that normal amounts of NGF are available for binding to the p75 receptor and for retrograde transport to forebrain cholinergic cells, however, these neurons do not respond by producing the ChAT protein that is necessary for the production of the neurotransmitter acetylcholine.