Electrochemical And Histochemical Study On The Relationship Between High Brain Iron And Degeneration Of Dopaminergic Neurons In The Substantia Nigra Of Rats

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons originating in the zona compacta of the substantia nigra (SNc) and terminating in the striatum (Str). Extensive studies have indicated that iron levels inceased in the SNc of parkinsonian patients. Due to its intrinsic ability to catalyze the formation of free radicals, it could participate in the cascade of events ending in cell death. Therefore, the increase of iron content may be involved in the etiology of PD. The recently described pathology of Parkinson's disease supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN and within the melanized dopamine neurons. In the present study, we made acute and chronic iron-overloaded rats by iron dextran. Using fast cyclic voltammetry (FCV), tyrosine hydroxylase (TH) immuohistochemistry, Perls' iron staining, high performance liquid chromatography-electrochemical detection (HPLC-ECD), we investigated the release of DA in Str by electrical stimulation of medial forbrain bundle(MFB) and the contents of DA and its metabolits dihydroxy-phenylacetic acid (DOPAC) and homovanillic (HVA) in Str, the survival of DA neurons and the changes of iron in SN. The results were as follows:1. In the group of acute and chronic iron overloaded rats, DA release in Str was lower than that of the normal group (P<0.05). DA release was much lower in the group of chronic than the group of acute (P<0.05).2. In the group of acute and chronic iron overloaded rats, the content of DA and its metabolits DOPAC, HVA in Str decreased significantly, compared with that of the normal group (P<0.05). The content of DOPAC much decreased in the group of chronic than the group of acute (P<0.05).3. In the group of acute and chronic iron overloaded rats, the numbers of TH immunoreactive neurons in SN were observed reduced significantly, compared with that of the normal group (P<0.05). The numbers of TH immunoreactive neurons was further reduced in the chronic iron overloaded group than the acute iron overloaded group (P<0.05).4. Iron staining in SN increased both in the group of acute and chronic iron overloaded rats, compared with that of the normal group (PO.05). Comparing the group of chronic to the group of acute, the SN showed a further increase in iron staining (PO.05).The above results strongly suggest that high iron in brain may be involved in the process of death of DA neurons. Peripheral iron dextran injection can increase the iron content in SN, resulting in the death of DA neurons. The damage of the chronic iron overload to DA neurons is stronger than the acute iron overload. It provides experimental evidence for the participant of high brain iron in the etiology of PD and suggests a way to make a new chelator to reduce high brain iron for the prevention and treatment of PD.