Reduced nerve growth factor in Rett syndrome postmortem brain tissue

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.