Increased Serum Lithium Level due to Mild to Moderate damage to Dopaminergic Neurons of the Substantia Nigra, Evidence from Animal Model of Parkinson’s Disease induced by 6-Hydoxydopamine

Background and Aim:

 It has been reported that lithium (Li) has neuroprotective effects in neurodegenerative diseases. In this study, we investigated the association between serum Li level and Parkinson’s disease induced by 6-hydroxypapamine (6-OHDA) in rats.

6-OHDA was injected into the medial forebrain bundle by stereotoxic surgery. Apomorphine- induced rotational and cylinder tests were carried out before the toxin injection and in the second and sixth weeks thereafter. Blood samples were collected from the heart of the animals in the seventh week. The survival of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) was determined using immunohistochemistry. Li was measured by ion selective electrode method (ISE).

There was no significant difference in the serum Li levels between control and 6-OHDA-treated rats. Based on the severity of the rotational behavior, the 6- OHDA- treated rats were divided into two subgroups: symptomatic (with severe behavioral symptoms) and asymptomatic (with no or mild behavioral symptoms). In the symptomatic and asymptomatic subgroups, SNc DA neuronal loss was 83 ± 16% and 45± 10%, respectively. Serum li level in the asymptomatic subgroup was significantly higher than that in the symptomatic subgroup and control group.

Serum Li level increased in the mild to moderate damage to SNc DA neurons but returned to normal value in severe neuronal damage. Therefore, an increase in serum Li level can predict subclinical SNc DA neuronal death and helps in making early diagnosis of PD.