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

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Abstract

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.

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Abbreviations

AcbC:

Accumbens nucleus core

Amyg:

Amygdala

BBB:

Blood–brain barrier

BNST:

Bed nucleus of stria terminalis

CA2/3:

CA2/CA3 of hippocampus

Cb ant/post:

Cerebellum anterior lobe/posterior lobe

CNS:

Central nervous system

CPu:

Caudate-putamen (striatum)

DG:

Dentate gyrus of hippocampus

DH:

Dorsal hypothalamus

Iba-1:

Ionized calcium-binding adapter molecule-1

LH:

Lateral hypothalamic

LPAG:

Lateral periaqueductal gray

LPS:

Lipopolysaccharide

MEnt:

Medial entorhinal cortex

MFC:

Medial frontal cortex

PFC:

Prefrontal cortex

Pir:

Piriform cortex

Pn:

Pontine nucleus

SN:

Substantia nigra

SC:

Superior colliculus

S1:

Sensory cortex, trunk region

TNFα:

Tumor-necrosis factor α

TNFR1:

Tumor-necrosis factor receptor 1

VA:

Ventral anterior thalamic nucleus

V1:

Visual cortex

VTA:

Ventral tegmental area

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Acknowledgments

This work was supported by National Science council (NSC 99-2320-B-006-017-MY3 and NSC99-2314-B-214-008) of Taiwan.

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Authors and Affiliations

  1. Department of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan

    Ting-Ting Yang

  2. Department of Physiology, China Medical University, Taichung, Taiwan

    Chingju Lin

  3. Department of Pathology, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan

    Chao-Tien Hsu & Tzu-Feng Wang

  4. Department of Cell Biology and Anatomy, National Cheng Kung University, 1 Ta Hsueh Road, Tainan, 70101, Taiwan

    Fang-Yi Ke & Yu-Min Kuo

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  1. Ting-Ting Yang
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Correspondence to Ting-Ting Yang or Yu-Min Kuo.

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Yang, TT., Lin, C., Hsu, CT. et al. Differential distribution and activation of microglia in the brain of male C57BL/6J mice. Brain Struct Funct 218, 1051–1060 (2013). https://doi.org/10.1007/s00429-012-0446-x

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