In vivo characterization of functional states of cortical microglia during peripheral inflammation.

Peripheral inflammation is known to trigger a mirror inflammatory response in the brain, involving brain's innate immune cells - microglia. However, the functional phenotypes, which these cells adopt in the course of peripheral inflammation, remain obscure. In vivo two-photon imaging of microglial Ca signaling as well as process motility reveals two distinct functional states of cortical microglia during a lipopolysaccharide-induced peripheral inflammation: an early "sensor state" characterized by dramatically increased intracellular Ca signaling but ramified morphology and a later "effector state" characterized by slow normalization of intracellular Ca signaling but hypertrophic morphology, substantial IL-1β production in a subset of cells as well as increased velocity of directed process extension and loss of coordination between individual processes.

Impairment of in vivo calcium signaling in amyloid plaque-associated microglia.

Neuroinflammation is a hallmark of Alzheimer's disease (AD) both in man and in multiple mouse models, and epidemiological studies link the use of anti-inflammatory drugs with a reduced risk of developing the disease. AD-related neuroinflammation is largely mediated by microglia, the main immune cells of the central nervous system. In vitro, executive functions of microglia are regulated by intracellular Ca(2+) signals, but little is known about microglial Ca(2+) signaling in vivo.

Cleaved caspase-3 expression in hypothalamic magnocellular neurons may affect vasopressin secretion during experimental polymicrobial sepsis.

We investigated whether the vasopressin (AVP) secretion deficiency observed during cecal ligation and puncture (CLP)-induced sepsis may be caused by apoptosis in hypothalamic magnocellular neurons. Plasma cytokines (TNF-α, IL-1β and IL-6) and nitrate levels were increased during sepsis and plasma AVP levels were higher in the early phase returning to basal levels in the late phase. Concomitantly, expression of the apoptosis effector, cleaved caspase 3, was increased in magnocellular neurons, inferring that this increase in hypothalamic neurons may be caused by cytokines and elevated nitrate levels.

The CST3 BB genotype and low cystatin C cerebrospinal fluid levels are associated with dementia in Lewy body disease.

A large proportion of demented Lewy body disease patients have Alzheimer's disease (AD)- like pathology, in particular amyloid-beta (Abeta) plaques. Cystatin C (CysC) is a carrier of soluble Abeta (42) in the cerebrospinal fluid (CSF) and reduces Abeta plaque formation. The CST3 BB genotype leads to a reduced secretion of the protein in vitro and increases the risk for AD, suggesting that variability in the CST3 gene and CysC protein concentration may be associated with dementia in Lewy body disease.