To determine whether reduced nerve growth factor (NGF) and/or its high affi
nity receptor, trkA, play a role in the pathophysiology of Rett syndrome (R
S), we used immunohistochemistry in paraffin-embedded human autopsy brain t
issue to quantify NGF and trkA levels within the frontal cortex of 9 RS fem
ales and 10 female controls of similar age. The results showed a significan
t reduction of NGF expression in RS patients (p < 0.001). Specifically, all
RS brains exhibited NGF levels at or below the minimum level observed in c
ontrols. In 3 RS brains there was no NGF detected. TrkA expression was also
reduced in the RS group (p = 0.035). Interestingly, the expression of NGF
in the RS group was significantly related to the presence of cortical astro
gliosis (r = 0.91) as indicated by immunostaining for glial fibrillary acid
ic protein (GFAP). This suggests that while the signals for NGF production
during injury remain intact, the critical developmental signals required fo
r early NGF production are impaired.