Protective effect of Lithium Chloride against Trimethyltin-induced hippocampal degeneration and comorbid depression in rats

Pathophysiology of depression is a controversial issue. The present study aimed at investigating the pathophysiology of depression in trimethyltin (TMT) intoxication as a hippocampal degeneration inducer. The effect of Lithium Chloride (LiCl) chronic administration on the amelioration of depression symptoms was also investigated. The rats were injected with single dose of TMT (8 mg/kg intra-peritoneal). The three test groups received 20, 40 and 80 mg/kg of LiCl respectively. Likewise, the vehicle treated group received saline for fourteen day. In order to assess the depression level, the immobility time of the rats was measured in the forced swim test (FST) and tail suspension test (TST). Then, the serum levels of tumor necrotic factor alpha (TNF-α) and brain derived neurotrophic factor (BDNF) were measured. Histological methods were then used to determine degenerated neurons and cell density in the hippocampus. An increase in the immobility time in FST and TST was seen in the rats who received TMT, while the rats receiving LiCl showed a significantly decreased immobility. In addition, LiCl administration increased the serum level of BDNF, while it decreased the serum level of TNF –α after TMT intoxication. The number of degenerated neurons in CA1, CA2, CA3 and DG of LiCl-treated groups were lower than that of vehicle treated group. LiCl treatment increased hippocampal cell density, especially in CA3 subfield. Taken together, the findings suggested that chronic administration of Lithium Chloride could ameliorate TMT-induced depression through up-regulation of BDNF and TNF-α signaling pathway.