Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1

Blue light exposure in vitro causes toxicity to trigeminal neurons and glia through increased superoxide and hydrogen peroxide generation

International audienceToday the noxiousness of blue light from natural and particularly artificial (fluorescent tubes, LED panels, visual displays) sources is actively discussed in the context of various ocular diseases. Many of them have an important neurologic component and are associated with ocular pain. This neuropathic signal is provided by nociceptive neurons from trigeminal ganglia. However, the phototoxicity of blue light on trigeminal neurons has not been explored so far. The aim of the present in vitro study was to investigate the cytotoxic impact of various wavebands of visible light (410-630 nm) on primary cell culture of mouse trigeminal neural and glial cells. Three-hour exposure to narrow wavebands of blue light centered at 410, 440 and 480 nm of average 1.1 mW/cm2 irradiance provoked cell death, altered cell morphology and induced oxidative stress and inflammation. These effects were not observed for other tested visible wavebands. We observed that neurons and glial cells processed the light signal in different manner, in terms of resulting superoxide and hydrogen peroxide generation, inflammatory biomarkers expression and phototoxic mitochondrial damage. We analyzed the pathways of photic signal reception, and we proposed that, in trigeminal cells, in addition to widely known mitochondria-mediated light absorption, light could be received by means of non-visual opsins, melanopsin (opn4) and neuropsin (opn5). We also investigated the mechanisms underlying the observed phototoxicity, further suggesting an important role of the endoplasmic reticulum in neuronal transmission of blue-light-toxic message. Taken together, our results give some insight into circuit of tangled pain and photosensitivity frequently observed in patients consulting for these ocular symptoms