Secretoneurin promotes pertussis toxin‐sensitive neurite outgrowth in cerebellar granule cells

Abstract

The neuropeptide secretoneurin (SN) is an endoproteolytic product of the chromogranin secretogranin II. We investigated the effects of SN on the differentiation of immature cerebellar granule cells derived from the external granular layer (EGL). Secretoneurin caused concentration-dependent increases in neurite outgrowth, reflecting differentiation. The maximum effect was reached at a concentration of 100 nM SN. Secretoneurin immunoneutralization using specific antiserum significantly decreased neurite outgrowth; however, neurite morphology was altered. An affinity chromatography-purified antibody significantly inhibited the outgrowth response to SN ( p < 0.001) without altering the morphology. Binding studies suggest the existence of specific G-protein-coupled receptors on the surface of monocytes that recognize SN. Assuming that SN promotes neurite outgrowth in EGL cells by acting through a similar G-protein-coupled mechanism, we treated SN-stimulated EGL cultures with pertussis toxin. Exposure to pertussis toxin (0.1 lg/mL) showed a significant inhibition of the SN-induced outgrowth. To establish a second messenger pathway we used the protein kinase C inhibitor staurosporine. We found that EGL cell viability was not enhanced following chronic SN treatment for 24 h. These data indicate that SN is a novel trophic substance that can affect cerebellar maturation, primarily by accelerating granule cell differentiation through a signalling mechanism that is coupled to pertussis toxin-sensitive G-proteins.

The Neuropeptide Secretoneurin Acts as a Direct Angiogenic Cytokine In Vitro and In Vivo

“…31 This is in contrast to our findings on ECs and to the observations made with VEGF on neuronal cells. 24 Presently, we can only speculate what mechanisms cause these differences.…”

“…24 Presently, we can only speculate what mechanisms cause these differences. One possible explanation would be the use of different neuronal cells in these studies (superior cervical ganglia and dorsal root ganglion cells 24 versus granular cells of the cerebellum 31 ).…”

Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke

“…*P < 0.05, **P < 0.01 vs. control. In agreement with previous studies, we found SN to have functions similar to those of glial cell-derived neurotrophic factor (GDNF), correlated to growth (18,(22)(23)(24) and repair (6,25,26) of injured neural tissue. Some literature has indicated that expression of SN is upregulated after cerebral ischemic insult (7).…”

“…In several recent reports, chromogranin/SN proteins have been found to be closely correlated with synaptic disturbance caused by neuronal/ glial and inflammatory mechanisms in conditions such as Alzheimer disease (3)(4)(5). It has also been reported that SN can promote the neurite outgrowth of immature cerebellar granule cells (6). Furthermore, in a recent report, increased expression of SN was found in an animal model after transient forebrain ischemia (7).…”

NG2 Glia: Novel Roles beyond Re-/Myelination

“…study of freshly sorted adult human NG2 glia [125] Neurotransmission [171,172] Chromogranin C, Chgc Gene expr. study of freshly sorted adult human NG2 glia [125] Neurite outgrowth [173] and angiogenesis [174].…”