Ectopic Tyrosine Hydroxylase-immunoreactive Neurons in the 6-OHDA-lesioned Striatum in Neonatal Rat

Hann, Hoo Jae

Abstract

Tyrosine hydroxylase-immunoreactive (TH-IR) neurons are known to exist in the substantia nigra pars compacta (SNpc), but not in the striatum in normal rats. In this study, injection of 6-OHDA into the 7 or 14 day neonatal rat striatum resulted in the appearance of ectopic TH-IR neurons in striatum. TH-IR cells were observed as early as postlesion day 3 and confirmed as neurons by TH/NeuN double immunohistochemistry. One or two neurons were found in most striatal sections at post-lesion day 4 where they were preferentially located in the ventro-lateral striatum, striatopallidal junction and globus pallidus. A small portion of these neurons persisted at least until post-lesion day 56, the oldest age studied. TH-IR neurons were found bilaterally in 6-OHDA-lesioned animals, but never in normal or vehicle-injected controls. To determine if these neurons resulted from stem cells, bromodeoxyuridine (BrdU) was injected daily for the first five days to label dividing cells. There was no co-localization of TH and BrdU immunoreactivity, excluding the possibility of stem cells as the source of these neurons. Although the TH-IR neurons were not numerous, their appearance following injury to the nigrostriatal system suggests that there is a capacity in neonatal brain to compensate for this lesion by upregulating dopaminergic phenotypic characters in pre-existing cells. The mechanism underlying this interesting phenotypic plasticity is unknown, but may be relevant to developing novel therapies for Parkinson's disease through stimulation of the brain's own potential for repair.