Brain Structure and Function

, Volume 218, Issue 4, pp 1051–1060 | Cite as

Differential distribution and activation of microglia in the brain of male C57BL/6J mice

Original Article


Upon certain stimuli, microglia undergo different degrees of transformation in order to maintain homeostasis of the CNS. However, chronic microglia activation has been suggested to play an active role in the pathogenesis of neurodegenerative diseases. The density of microglia and the degree of microglia activation vary among brain regions; such differences may underlie the brain region-specific characteristics of neurodegenerative diseases. In this study, we aim to characterize the temporal and spatial profiles of microglia activation induced by peripheral inflammation in male C57BL/6J mice. Our results showed that, on average, microglia densities were highest in the cortex, followed by the limbic area, basal nuclei, diencephalon, brainstem and cerebellum. Among the 22 examined brain nuclei/regions, the substantia nigra had the highest microglia density. Microglia morphological changes were evident within 3 h after a single intraperitoneal lipopolysaccharides injection, with the highest degree of changes also in the substantia nigra. The lipopolysaccharide-induced microglia activation, determined by maximal cell size, was positively correlated with density of microglia and levels of TNFα receptor 1; it was not correlated with original microglia cell size or integrity of blood–brain barrier. The differential response of microglia also cannot be explained by different types of neurotransmitters. Our works suggest that the high density of microglia and the high levels of TNFα receptor 1 in the substantia nigra make this brain region the most susceptible area to systemic immunological insults.


Microglia TNFα receptor 1 Substantia nigra Systemic inflammation LPS Mouse 



Accumbens nucleus core




Blood–brain barrier


Bed nucleus of stria terminalis


CA2/CA3 of hippocampus

Cb ant/post

Cerebellum anterior lobe/posterior lobe


Central nervous system


Caudate-putamen (striatum)


Dentate gyrus of hippocampus


Dorsal hypothalamus


Ionized calcium-binding adapter molecule-1


Lateral hypothalamic


Lateral periaqueductal gray




Medial entorhinal cortex


Medial frontal cortex


Prefrontal cortex


Piriform cortex


Pontine nucleus


Substantia nigra


Superior colliculus


Sensory cortex, trunk region


Tumor-necrosis factor α


Tumor-necrosis factor receptor 1


Ventral anterior thalamic nucleus


Visual cortex


Ventral tegmental area


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Chinese Medicine for Post-BaccalaureateI-Shou UniversityKaohsiungTaiwan
  2. 2.Department of PhysiologyChina Medical UniversityTaichungTaiwan
  3. 3.Department of PathologyE-Da Hospital and I-Shou UniversityKaohsiungTaiwan
  4. 4.Department of Cell Biology and AnatomyNational Cheng Kung UniversityTainanTaiwan

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