Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning

Miyatake

et al. 2006

Neuropsychopharmacol

156

149

Long-term exposure to pyschostimulants and opioids induced neuronal plasticity. Accumulating evidence suggests that astrocytes actively participate in synaptic plasticity. We show here that a glial modulator propentofylline (PPF) dramatically diminished the activation of astrocytes induced by drugs of abuse, such as methamphetamine (METH) and morphine (MRP). In vivo treatment with PPF also suppressed both METH-and MRP-induced rewarding effects. On the other hand, intra-nucleus accumbens (N.Acc.) administration of astrocyte-conditioned medium (ACM) aggravated the development of rewarding effects induced by METH and MRP via the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, which modulates astrogliosis and/or astrogliogenesis. Furthermore, ACM, but not METH itself, clearly induced the differentiation of multipotent neuronal stem cells into glial fibrillary acidic protein-positive astrocytes, and this effect was reversed by cotreatment with the Jak/STAT inhibitor AG490. Intra-cingulate cortex (CG) administration of ACM also enhanced the rewarding effect induced by METH and MRP. In contrast to ACM, intra-N.Acc. administration of microglia-conditioned medium failed to affect the rewarding effects of METH and MRP in mice. These findings suggest that astrocyte-, but not microglia-, related soluble factors could amplify the development of rewarding effect of METH and MRP in the N.Acc. and CG. The present study provides direct evidence that astrocytes may, at least in part, contribute to the synaptic plasticity induced by drugs of abuse during the development of rewarding effects induced by psychostimulants and opioids.

Section: Discussionmentioning

confidence: 99%

Direct Evidence of Astrocytic Modulation in the Development of Rewarding Effects Induced by Drugs of Abuse

Miyatake

et al. 2006

Neuropsychopharmacol

156

149

“…Each chemokine binds to one or more specific G-protein-coupled receptor. Chemokines have traditionally been associated with inflammatory responses, but recently have been associated with more diverse roles including regulating the migration and survival of neurons (Menniken et al 1999;Chalasani et al 2003a,b;Belmadani et al 2005). For example, IL-8 promotes survival of hippocampal neurons (Araujo and Cotman 1993) and stromal-cell-derived factor 1 (SDF-1) promotes survival of retinal ganglion cells, even in the absence of neurotrophins (Chalasani et al 2003b).…”

Section: Discussionmentioning

confidence: 99%

Immortalized Mouse Inner Ear Cell Lines Demonstrate a Role for Chemokines in Promoting the Growth of Developing Statoacoustic Ganglion Neurons

Bianchi

Daruwalla

Roth

et al. 2005

JARO

The target-derived factors necessary for promoting initial outgrowth from the statoacoustic ganglion (SAG) to the inner ear have not been fully characterized. In the present study, conditioned medium from embryonic Immortomouse inner ear cell lines that maintain many characteristics of developing inner ear sensory epithelia were screened for neurite-promoting activity. Conditioned medium found to be positive for promoting SAG neurite outgrowth and neuronal survival was then tested for the presence of chemokines, molecules that have not previously been investigated for promoting SAG outgrowth. One candidate molecule, monocyte chemotactic protein 1 (MCP-1), was detected in the conditioned medium and subsequently localized to mouse hair cells by immunocytochemistry. In vitro studies demonstrated that function-blocking MCP-1 antibodies decreased the amount of SAG neurite outgrowth induced by the conditioned medium and that subsequent addition of MCP-1 protein was able to promote outgrowth when added to the antibodytreated conditioned medium. The use of the Immortomouse cell lines proved valuable in identifying this candidate cofactor that promotes outgrowth of earlystage SAG nerve fibers and is expressed in embryonic hair cells.

Journal of Neuroimmunology

“…Therefore, we focused on a concentration range known to have biological activity in our system and CXCL10 was tested at 50, 100 and 250 nM. These concentrations are likely to reflect pathophysiological conditions because CXCL10 levels in the normal brain are low or undetectable (Mennicken et al, 1999). For example, CXCL10 levels in the CSF of humans under normal conditions are around 100 pg/ml (Galimberti et al, 2006) but can increase as much as 50 fold during pathophysiological conditions such as CNS inflection (Cinque et al, 2005).…”

Section: Cxcl10 Treatmentmentioning

confidence: 99%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-κB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-κB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-κB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.