Dopaminergic and serotonergic neurotransmitters in bone marrow transplant patients

Depigmentation of neurons in the substantia nigra (SN) is found in patients dying after bone marrow transplantation (BMT). This study examined neurochemical striatal changes related to BMT. Caudate nucleus and putamen of 6 BMT subjects and 10 age-matched controls were analyzed for levels of dopamine (DA), homovanillic acid (HVA), 5-hydroxyindoleamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA), by high pressure liquid chromatography-electron capture detection (HPLC-ECD). In addition, assays of the enzymatic activities of monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) were performed. Cholinergic markers, ChAT and AChE, were reduced in BMT caudate (p < 0.05) but not in the putamen. A recovery toward normal cholinergic enzymatic activity was identified with increased post-transplant survival time. The level of DA was reduced 50% in BMT caudate and putamen while HVA was increased 30%, however, neither reduction achieved statistical significance. Increasing post-transplant survival time correlated with decreased levels of DA in caudate nucleus and putamen in the early post-transplant period, while HVA was increased over the same interval but tended to return to normal levels with increasing survival time. Two-fold increases of BMT caudate 5-HT (p < 0.003) and 5-HIAA were found; similar changes were noted in putamen 5-HT and 5-HIAA (p < 0.0008). Significant increases in MAO-A and B were found in BMT caudate (p < 0.0001 and p < 0.06, respectively) and putamen (p < 0.0005 and p < 0.006, respectively). No statistically significant changes were noted in the 5-HT, 5-HIAA, or MAO A or MAO B with increasing post-transplant survival. Whether these changes are the result of physiologic or toxic effects is unknown.