Objective: To investigate the changes in behavioristics, substantia nigra tyrosine hydroxylase (TH) immunoreactive cells, and ultrastructure of substantia nigra neurons in rats after manganese exposure via intracerebral injection.
Methods: A total of 72 healthy male Sprague-Dawley rats were randomly divided into exposure group and control group, with 36 rats in each group. The stereotactic technique was used for injection of 1 μl MnCl2·4H2O (1 mol/L) into the corpus striatum in the exposure group, and the control group was injected with the same volume of normal saline. The changes in rotational behavior, number of TH immunoreactive cells in the substantia nigra, and ultrastructure of the substantia nigra induced by apomorphine were observed at 8 hours and 1, 3, 7, 15, and 30 days after injection, and this measure was compared with manganese exposure via intraperitoneal injection.
Results: After apomorphine induction for 30 minutes, the exposure group showed a gradual increase in the number of rotations over the time of manganese exposure (F= 176.921, P<0.01) and a significantly higher number of rotations than the control group (F=482.654, P<0.01). The exposure group showed a gradual reduction in the mean A value of TH immunoreactive cells in the injured substantia nigra over the time of exposure (F=12.009, P<0.01) , and this value differed significantly between the injured substantia nigra in the exposure group and the contralateral substantia nigra in the exposure group and the injured side in the control group (F=36.131, P<0.01). At 3, 7, 15, and 30 days after exposure, the injured substantia nigra showed a significantly lower mean A value of TH immunoreactive cells than the contralateral side in the exposure group (all P<0.01). At 7, 15, and 30 days, the injured substantia nigra in the exposure group showed a significantly lower mean A value than the injured side in the control group (all P<0.01). After manganese exposure, substantia nigra neurons showed the changes including mitochondrial swelling, dilatation of the endoplasmic reticulum, and demyelination of nerve fibers in different stages, which suggested the dynamic process of dopaminergic neuron injuries. Compared with manganese exposure via intraperitoneal injection, manganese exposure via intracerebral injection can induce behavioral changes and injuries of the substantia nigra-striatum system more quickly.
Conclusion: Manganese exposure via intracerebral injection induces behavioral changes and injuries of substantia nigra dopaminergic neurons in rats within a short time.