Glial- and Neuronal-Specific Expression of CCL5 mRNA in the Rat Brain

Abstract

Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia. In the central nervous system (CNS), CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins. Evidence has also suggested that this chemokine may regulate opioid response. The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression. In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes, astrocytes and microglia. Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus. Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.

Ccl5 Mediates Proper Wiring of Feedforward and Lateral Inhibition Pathways in the Inner Retina

“…In the mature CNS, Ccl5 signaling linked to both inhibitory and glutamatergic neurotransmission. Ccl5 and Ccr expression is present within the ventral tegmental area, nucleus accumbens, striatum, prefrontal cortex, hippocampus, striatum and frontal cortex ( Szabo et al, 2002 ; Campbell et al, 2013 ; Mocchetti et al, 2013 ; Fe Lanfranco et al, 2018 ). Given expression of Ccl5 and Ccrs are associated with known brain circuits, i.e., dopaminergic mesolimbic pathway, and can modulate neurotransmission, it has been proposed that chemokines may serve as a third neurotransmitter system in the CNS ( Adler and Rogers, 2005 ).…”

“…Like other chemokines, Ccl5, formerly known as RANTES, is classically associated with chemotaxis and immune cell migration ( Rossi and Zlotnik, 2000 ; Appay and Rowland-Jones, 2001 ). However, studies elsewhere in the CNS suggest that Ccl5 and its receptors are also constitutively expressed by neurons and glia ( He et al, 1997 ; Babcock et al, 2003 ; Pham et al, 2005 ; Subileau et al, 2009 ; Sorce et al, 2011 ; Fe Lanfranco et al, 2018 ) and may play a role in neuron survival, development and neurotransmission ( Galasso et al, 1998 ; Mennicken et al, 2002 ; Gamo et al, 2008 ; Sorce et al, 2010 , 2011 ; Tripathy et al, 2010 ).…”

Oxymatrine Attenuates Dopaminergic Neuronal Damage and Microglia-Mediated Neuroinflammation Through Cathepsin D-Dependent HMGB1/TLR4/NF-κB Pathway in Parkinson’s Disease

“…The quantitative analysis of Immunofluorescence assay was performed as previously described (Lanfranco et al, 2017;Takizawa et al, 2017). Briefly, for TH immunofluorescence staining, 10 areas were randomly selected from the brain tissue slides or mice primary microglia coverslips in each group.…”

<b>Gnetin C suppresses double-stranded RNA-induced C-C motif chemokine ligand 2 (CCL2) and CCL5 production by inhibiting Toll-like receptor 3 signaling </b><b>pathway </b>

“…Chemokines are small, 8-to 12-kDa cytokines that have the ability to induce the chemotaxis of leukocytes and are divided into four groups based on their initial cysteine residue: XC, CC, CXC, and CX3C (24). Among them, CCL2 and CCL5 are produced by various cell types in the brain, such as neurons, astrocytes, and microglia (15,20), and are suggested to be involved in viral and autoimmune inflammatory neurological disorders (1,13). Previous infection with Epstein-Bar virus may contribute to the development of multiple sclerosis (17), and elevated levels of CCL2 and CCL5 are associated with the activity of this disease (3,29).…”