在中樞神經系統中，多巴胺神經元主要分佈於中腦腹側被蓋腦區及黑質腦區中。中腦黑質腦區多巴胺神經元的數目會隨著年紀增加而減少，但此一老化現象在腹側被蓋腦區則仍不清楚。先前的文獻指出，多巴胺神經元對微小膠細胞的活化及其活化後釋放的發炎相關物質具高敏感性。而且，老化已知會增加微小膠細胞的活化程度。本研究的目的是比較老化或發炎，對黑質腦區及腹側被蓋腦區中，微小膠細胞活化程度和多巴胺神經元數目之影響。我們以免疫組織化學法對多巴胺神經元和微小膠細胞進行染色，以計數其數目和量測形態之變化。在老化的實驗部分，我們比較3、6、9、12個月大的公小鼠，發現黑質腦區中微小膠細胞的密度和活化程度，隨年齡增加而增加，而多巴胺神經元的數目則隨之減少。此現象在腹側被蓋腦區則不顯著。接著，我們針對3個月大的小鼠進行分析，發現黑質腦區的微小膠細胞分支數明顯多於腹側被蓋區。於是我們進一步比較新生小鼠黑質腦區和腹側被蓋區的微小膠細胞，結果發現兩腦區微小膠細胞的密度和活化程度並無不同。顯示黑質腦區在出生後，微小膠細胞的密度會逐漸升高。在發炎的實驗部分，我們分別比較不同的注射位置(腹腔或腦內)、不同的脂多醣濃度（0.15或1毫克/公斤）、不同的犧牲時間(3或24小時)，對微小膠細胞活化程度和多巴胺神經元數目之影響。腹腔注射的結果顯示，黑質腦區的微小膠細胞的密度和活化程度，在兩種脂多醣濃度的刺激下，都比腹側被蓋區高。在脂多醣注射24小時後，黑質腦區多巴胺神經元數目減少的情形，比腹側被蓋區更為顯著。腦內注射的結果顯示，脂多醣直接注射於黑質腦區3小時後，所誘發的微小膠細胞個別活化程度，比直接注射於腹側被蓋區高；黑質腦區多巴胺神經元減少的數目，也較腹側被蓋區顯著。腦內注射脂多醣24小時後，在黑質腦區和腹側被蓋區均造成微小膠細胞和多巴胺神經元非常嚴重的死亡，所以無法準確定量。總結本研究，黑質腦區中多巴胺神經元的數目，會隨著老化而下降，但是此一現象在腹側被蓋腦區則不明顯。這可能是因為黑質腦區中微小膠細胞的密度較高，造成區域內的發炎反應較大。但是，黑質腦區中微小膠細胞的密度於出生後兩天時，跟腹側被蓋腦區比較並無不同。但是，為何出生後微小膠細胞的密度在黑質腦區快速倍增，而在腹側被蓋腦區只有緩慢增加則有待後續實驗釐清。

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 µl, 25 µg/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.

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