Microglial proliferation attenuates sickness responses in adult mice during endotoxin-induced inflammation.

We previously reported that the single peripheral administration of lipopolysaccharide (LPS) induced robust and transient microglial proliferation or increased the microglial population in the circumventricular organs (CVOs) and other regions, including the hypothalamus, medulla oblongata, and limbic system. However, the functional significance of an increased microglial population during endotoxin-induced inflammation remains unclear. The present study showed microglial proliferation in the mouse brain during inflammation induced by 50 mg/kg zymosan, 160 nmol/kg prostaglandin E, and 5 mg/kg LPS.

Depletion of microglia and macrophages with clodronate liposomes attenuates zymosan-induced Fos expression and hypothermia in the adult mouse.

Toll-like receptor 2 (TLR2) recognizes a wide range of microbial molecules and plays critical roles in the initiation of innate immune responses. In the present study, we aimed to investigate whether the depletion of microglia and macrophages with clodronate liposomes (Clod-Lips) attenuates the activation of mouse brain circuits for TLR2-mediated inflammation and hypothermia. The peripheral administration of the TLR2 agonist zymosan induced nuclear factor-κB activation in microglia and macrophages and Fos expression in astrocytes/tanycytes and neurons in the circumventricular organs (CVOs).

Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation.

Numerous studies have reported the importance of microglial activation in various pathological conditions, whereas little attention has been given to the point for dynamics of microglial population under infection-induced inflammation. In the present study, the single systemic stimulation of 100 μg/kg lipopolysaccharide (LPS) induced robust microglial proliferation only in the circumventricular organs (CVOs) and their neighboring brain regions. More than half of microglia similarly showed proliferative activity in the CVOs and their neighboring brain regions after 1 mg/kg LPS stimulation, while this stimulation expanded microglia-proliferating brain regions including the hypothalamus, medulla oblongata, and limbic system.

Microglia are continuously activated in the circumventricular organs of mouse brain.

Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes. Moreover, microglia in the CVOs showed the strong protein expression of the M1 markers CD16/32 and CD86 and M2 markers CD206 and Ym1 without any pathological stimulation.

Lifespan extension in the spontaneous dwarf rat and enhanced resistance to hyperoxia-induced mortality.

Lifespan extension has been demonstrated in dwarfism mouse models relative to their wild-type. The spontaneous dwarf rat (SDR) was isolated from a closed colony of Sprague-Dawley (SD) rats. Growth hormone deficiencies have been indicated to be responsible for dwarfism in SDR.

Spontaneous dwarf rat: a novel model for aging research.

Aim: Dwarf animal models can provide new models for aging research. For the spontaneous dwarf rat (SDR), a dwarf strain derived from the Sprague-Dawley (SD) rat, no data relevant to aging research are available. The present study aimed to examine its growth, hormonal background, lifespan and age-related diseases.