Translocator protein (18 kDa) is involved in the regulation of reactive gliosis

Abstract

Translocator protein (18 kDa) (TSPO), previously known as peripheral‐type benzodiazepine receptor, is a critical component of the mitochondrial permeability transition pore. Brain inflammation results in the induction of the expression of TSPO in glial cells and some TSPO ligands decrease reactive gliosis after brain injury. However, since some TSPO ligands are neuroprotective, their effects on reactive gliosis may be the consequence of a reduced neurodegeneration. To assess whether TSPO ligands can modulate reactive gliosis in absence of neuronal death, we have tested their effects on the inflammatory response induced in the hippocampus of male rats by the intracerebroventricular infusion of lipopolysaccharide (LPS). LPS treatment did not induce neuronal death, assessed by Fluoro jade‐B staining, but increased the number of cells immunoreactive for vimentin and MHC‐II, used as markers of reactive astrocytes and reactive microglia, respectively. Furthermore, LPS produced an increase in the number of proliferating microglia. The TSPO ligand PK11195 reduced the number of MHC‐II immunoreactive cells and the proliferation of microglia in LPS treated rats. In contrast, another TSPO ligand, Ro5‐4864, did not significantly affect the response of microglia to LPS. Neither PK11195 nor Ro5‐4864 affected the LPS‐mediated increase in the number of vimentin‐immunoreactive astrocytes at the time point studied, although PK11195 reduced vimentin immunoreactivity. These findings identify TSPO as a potential target for controlling neural inflammation, showing that the TSPO ligand PK11195 may reduce microglia activation by a mechanism that is independent of the regulation of neuronal survival. © 2007 Wiley‐Liss, Inc.

Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide

“…After ischemic insult, activated astrocytes release high levels of nitric oxide, peroxynitrite, glutamate, TNF-α, and IL-1β [38,39]. Although there are some studies on astrocytes in the brain with LPS preconditioning [40][41][42], our finding indicates that the reduction of activated astrocytes may participate in a protective role of LPS preconditioning against ischemic damage.…”

Targeting the 18-kDa translocator protein: recent perspectives for neuroprotection

“…By stereotaxic injection of LPS into the substantia nigra (SN) of mouse brains, Bae et al [44] have investigated the antiinflammatory effects of PK11195 and Ro5-4864 in CNS; the reduction in the expression of ionized calcium binding adaptor molecule 1 (Iba-1) and NF-kB and inhibition of the release of iNOS, TNF-α and IL-6 have been evidenced in microglia of SN [44]. Similarly, the LPS infusion in the hippocampus of male rats has suggested that in vivo PK11195 administration has been able to reduce the number of major histocompatibility complex (MHC)-II immunoreactive cells and microglia proliferation; in contrast, Ro5-4864 does not significantly affect the response of microglia to LPS [47].…”

The relation between α-synuclein and microglia in Parkinson’s disease: Recent developments

“…163 In fact, we have shown in an alpha-synuclein model of 164 PD both in rodents and primates, that the microglia 165 response is early, preceding cell death, but not static 166 (Sanchez-Guajardo et al, 2010;Barkholt et al, 2012). 167 Also in vitro microglia's response to alpha-synuclein is 168 complex, with both pro and anti-inflammatory profiles 169 co-existing in parallel (Reynolds et al, 2008b to apoptosis (Veenman and Gavish, 2012), increased pro-188 liferation and phagocytosis (Choi et al, 2011) and its 189 modulation seems to be indeed involved in microglia acti-190 vation (Veiga et al, 2007). In addition, the limitation to (Gao et al, 2008).…”