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 signifi cant decline in number of choline acetyltransferase (ChAT)-containing neuro ns throughout the forebrain of RS girls. The loss of these ChAT-positive ce lls may be caused by a lack of nerve growth factor (NGF). In the current st udy, 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 tha t 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 cel ls. however, these neurons do not respond by producing the ChAT protein tha t is necessary for the production of the neurotransmitter acetylcholine.