Comparative analysis of microglia activation and dopaminergic neuron loss between substantia nigra and ventral tegmental area

摘要

In the central nervous system dopaminergic (DA) neurons are mainly located in the ventral tegmental area (VTA) and substantia nigra (SN) It has been known that the numbers of DA neuron in the SN decrease with age Whether similar event occurs in the VTA remains unknown Previous studies demonstrated that DA neurons are highly susceptible to microglial activation and pro-inflammatory cytotoxic factors Therefore the objective of this study was to compare the effects of aging and inflammation on the levels of microglia activation and DA number in the VTA and SN Microglia were labeled immunohistochemically by Iba-1 antibodies whereas DA neurons were labeled by tyrosine hydroxylase antibodies in mice with different ages (3 6 9 12 months) The results showed that the age-associated DA neuron loss was only evident in the SN but not in the VTA The degrees of age-associated microglia activation were more profound in the SN than in the VTA Furthermore microglia of the SN had more processes than that in the VTA at the age of 3 months Moreover the densities of microglia at 2-day-old mice were similar between two brain regions and largely increased after birth in the SN To compare the responses of microglia activation induced by LPS LPS was either injected to peritoneum (1 mg/kg 0 15 mg/kg) or directly to the SN and VTA (0 25 ?l 25 ?g/ml) of 2-month-old male C57BL/6 mice All groups were sacrificed at either 3h or 24h after the injection The results showed that the densities and degrees of activation of microglia in the SN were higher than those of VTA at 3 h and 24 h after intraperitoneal LPS injection Meanwhile the numbers of DA neuron loss were larger in the SN than that of VTA at 24 h after intraperitoneal LPS injection Similarly 3 h after LPS injection to the SN the degrees of microglia responses and DA neuron loss were more pronounced than those of the VTA Because LPS induced severe cell death in both brain regions 24 h after injection we failed to compare the numbers and morphological changes of microglia and DA neuron In conclusion the numbers of DA neurons in the SN decreases as age increased; while such changes are less significant in the VTA We suggest that the differential responses are caused by different microglia densities in these two brain regions; the higher microglia density will result in higher inflammatory reactions Interestingly the microglia densities of SN and VTA are similar at 2 d after birth The reasons for the different degrees of change in microglia density in these two brain regions await future characterization

獎項日期	2014 8月 20
原文	English
監督員	Yu-Min Kuo (Supervisor)