Investigation on the neuroinflammatory mechanism of iron-induced selective dopaminergic neurodegeneration / 中华神经科杂志

ABSTRACT

Objective To investigate the role and neuroinflammatory mechanism of iron on dopamine ( DA) neurons in multiple primary midbrain cultures that mimic human substantia nigra pars compacta.Methods Ferrous chloride ( Fe2+ ) with the desired concentrations of 5,25 and 100 μmol/L was used to ( 1 ) treat primary midbrain neuron-microglia-astroglia cultures for 7 days and the numbers of DA neurons and total neurons were counted after tyrosine hydroxylase (TH) and neuron-specific neuclear protein neurons in 5,25 and 100 μmol/L Fe2 + -treated groups were 89%,70% and 55% of control group,and 25,100 μmol/L Fe2+ significantly decreased DA neuronal numbers compared with control group ( F = 12.047,P ＜0.01);DA neuronal bodies were shrunk and smaller,cytoplasmic stainings were reduced,neuronal dendrites were decreased;(2) The numbers of Neu-N ( + ) total neurons in 5,25 and 100 μmol/L Fe2+-treated groups were 100%,104% and 101% of control group and Fe2+ did not decrease DA neuronal numbers compared with control group (t =4.458,P ＞ 0.05 );5,25 and 100 μmol/L Fe2+-induced difference between total neurons and DA neurons were 11%,34% and 46%,and 25 and 100 (Amol/L Fe2+ produced significant difference(t =8.098,P ＜0.05;t = 11.218,P＜0.05);(3) In primary midbrain neuron-microglia-astroglia and neuron-astroglia cultures,the numbers of DA neurons in 25 μmol/L Fe+-treated group were 70% and 98% of control group,respectively.The difference between two groups was 28%,which was statistically significant (t =8.061,P＜0.05);The numbers of DA neurons in 100 μmol/L groups were 183%,190 % and 240% of control group,and 25 and 100 μmol/L Fe2 + significantly increased microglial numbers compared with control group ( F = 6.101,P ＜ 0.01 );dramatic changes of microglial morphology were indicated by the enlarged cell bodies and irregular shape.Conclusions Fe2 + provokes selective DA neuronal damage and microglia are the mediators of the neurotoxic effect,which may be due to microglial over-activation featured by the significant production of neurotoxic factors and morphological changes of microglia.This investigation cast a new light for PD therapy by inhibiting Fe2+ -induced neuroinflammation characterized by the microglial over-activation.