Cells of the sympathoadrenal lineage: Biological properties as donor tissue for cell-replacement therapies for Parkinson's disease

Sympathoadrenal (SA) cell lineage encompasses neural crest derivatives such as sympathetic neurons, small intensely fluorescent (SIF) cells of sympathetic ganglia and adrenal medulla, and chromaffin cells of adrenal medulla and extra-adrenal paraganglia. SA autografts have been used for transplantation in Parkinson's disease (PD) for three reasons: (i) as autologous donor tissue avoids graft rejection and the need for immunosuppressant therapy, (ii) SA cells express dopaminotrophic factors such as GNDF and TGFβs, and (iii) although most of SA cells release noradrenaline, some of them are able to produce and release dopamine. Adrenal chromaffin cells were the first SA transplanted cells in both animal models of PD and PD patients. However, these autografts have met limited success because long-term cell survival is very poor, and this approach is no longer pursued clinically. Sympathetic neurons from the superior cervical ganglion have been also grafted in PD animal models and PD patients. Poor survival into brain parenchyma of grafted tissue is a serious disadvantage for its clinical application. However, cultured sympathetic cell grafts present a better survival rate, and they reduce the need for levodopa medication in PD patients by facilitating the conversion of exogenous levodopa. SA extra-adrenal chromaffin cells are located on paraganglia (i.e., the Zuckerkandl's organ), and have been used for grafting in a rodent model of PD. Preliminary results indicate that long-term survival of these cells is better than for other SA cells, exerting a more prolonged restorative neurotrophic action on denervated host striatum. The ability of SA extra-adrenal cells to respond to hypoxia, differently to SA sympathetic neurons or adrenal medulla cells, could explain their good survival rate after brain transplantation.     

Stress induces zinc finger immediate early genes in the rat adrenal gland

The secretion of steroid hormones from the adrenal cortex as well as cathecolamines from the adrenal medulla is stimulated by stress. In this study, we studied the effect of capsaicin-induced stress on the expression of the immediate-early genes (IEGs) NGFI-A, -B, -C, egr-2, -3 and Nurr1 in the rat adrenal gland using in situ hybridization. All of these IEGs except egr-2 were rapidly induced in the adrenal cortex and medulla. The temporal patterns of the IEG induction in medulla varied significantly. NGFI-A was induced in medulla within 15 min after stress, NGFI-B, egr-3 and Nurr1 were induced by 30 min, whereas NGFI-C was induced by 2 h. Surprisingly, only NGFI-B and Nurr1 were induced in the glucocorticoid secreting regions of zonae reticularis and fasciculata of the cortex, starting 15 min after the stress. All of the inducible IEGs were induced in the aldosterone secreting zona glomerulosa 15-30 min after the capsaicin injection. NGFI-A, NGFI-B and Nurr1 expression persisted for 6 h. Since the IEGs studied had major differences in their temporospatial induction pattern, they are likely to be induced by distinct stress-elicited factors and have separate target genes and roles in stress-induced glucocorticoid and catecholamine secretion.