The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes.

Pro-inflammatory cytokines have been implicated in the precipitation of depression and related disorders, and the antidepressant sensitive serotonin transporter (SERT) may be a major target for immune regulation in these disorders. Here, we focus on astrocytes, a major class of immune competent cells in the brain, to examine the effects of pro-longed treatment with tumor necrosis factor-alpha (TNF-α) on SERT activity. We first established that high-affinity serotonin uptake into C6 glioma cells occurs through a SERT-dependent mechanism.

The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells.

Localized tissue hypoxia is a feature of infection and inflammation, resulting in the upregulation of the transcription factors hypoxia-inducible factor 1α and nuclear factor κB (NF-κB) via inhibition of oxygen sensing hydroxylase enzymes. Previous studies have demonstrated a beneficial role for the hydroxylase inhibitor dimethyloxallyl glycine (DMOG) in inflammatory conditions, including experimental colitis, by regulating the activity of hypoxia-inducible factor 1 and NF-κB. We have demonstrated in vivo that pretreatment with DMOG attenuates systemic LPS-induced activation of the NF-κB pathway.

Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis.

Complement is implicated in the pathology of neurodegenerative and inflammatory disease in the central nervous system (CNS). Although studies demonstrate that inhibition of complement activation attenuates disease development in the CNS, the specific complement components that contribute to the pathogenesis of CNS diseases remain unclear. To dissect the role of C5a in CNS disease, we developed a transgenic mouse that produces C5a exclusively in the brain using the astrocyte-specific, murine glial fibrillary acidic protein (GFAP) promoter.

The differential response of astrocytes within the vestibular and cochlear nuclei following unilateral labyrinthectomy or vestibular afferent activity blockade by transtympanic tetrodotoxin injection in the rat.

In this study, we investigated whether changes in the vestibular neuronal activity per se influence the pattern of astrocytes morphology, glial fibrillary acidic protein (GFAP) expression and ultimately their activation within the vestibular nuclei after unilateral transtympanic tetrodotoxin (TTX) injections and after unilateral inner ear lesion. The rationale was that, theoretically the noninvasive pharmacological functional blockade of peripheral vestibular inputs with TTX, allowed us to dissociate the signals exclusively related to the shutdown of the resting activity of the first-order vestibular neurons and from neuronal signals associated with trans-ganglionic changes in first order vestibular neurons induced by unilateral labyrinthectomy (UL). Since the cochlea was removed during the surgical procedure, we also studied the astrocytic reaction within the deafferented cochlear nuclei.