Rabies virus infection is associated with alterations in the expression of parvalbumin and secretagogin in mice brain.

Infection with the deadly rabies virus (RABV) leads to alteration of cellular gene expression. The RABV, similar to other neurodegenerative diseases may be implicated in neuronal death due to an imbalance in Ca2+ homeostasis. Parvalbumin (PV) and Secretagogin (Scgn), two members of the Calcium-Binding Proteins (CBPs) are useful neuronal markers responsible for calcium regulation and buffering with possible protective roles against infections. This study investigated whether infection with rabies virus causes variance in expression levels of PV and Scgn using the Challenge virus standard (CVS) and Nigerian Street Rabies virus (SRV) strains. Forty-eight, 4-week-old BALB/c mice strains were divided into two test groups and challenged with Rabies virus (RABV) infection and one control group. The presence of RABV antigen was verified by direct fluorescent antibody test (DFAT) and real-time quantitative PCR (qRT-PCR) was used to assess PV and Scgn gene expression. Infection with both virus strains resulted in significant (p < 0.05) increases in expression during early infection. Mid-infection phase caused reduced expression for both genes. However, as infection progressed to the terminal phase, a lower increase in expression was measured. Gene expression and viral load correlation indicated no positive relationship. Neurons with these CBPs may have a greater capacity to buffer calcium and be more resistant to degenerative changes caused by RABV. This implies that, when PV and Scgn expression levels are kept adequately high, the integrity of neurons may be maintained and degeneration caused by RABV infection may be prevented or stopped, hence, these are possible constituents of effective rabies therapy.

Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans, rats, and mice.

Secretagogin (SCGN) is a recently discovered calcium-binding protein belonging to the group of EF-hand calcium-binding proteins. SCGN immunostaining has been described in various regions of the human, rat and mouse brain. In these studies, it has been reported that, in general, the patterns of SCGN staining differ between rodents and human brains. These differences have been interpreted as uncovering phylogenetic differences in SCGN expression. Nevertheless, an important aspect that is not usually taken into account is that different methods are used for obtaining and processing brain tissue coming from humans and experimental animals. This is a critical issue since it has been shown that post-mortem time delay and the method of fixation (i.e., perfused vs. nonperfused brains) may influence the results of the immunostaining. Thus, it is not clear whether differences found in comparative studies with the human brain are simply due to technical factors or species-specific differences. In the present study, we analyzed the pattern of SCGN immunostaining in the adult human hippocampal formation (DG, CA1, CA2, CA3, subiculum, presubiculum, and parasubiculum) as well as in the entorhinal and perirhinal cortices. This pattern of immunostaining was compared with rat and mouse that were fixed either by perfusion or immersion and with different post-mortem time delays (up to 5 hr) to mimic the way the human brain tissue is usually processed. We found a number of clear similarities and differences in the pattern of labeling among the human, rat, and mouse in these brain regions as well as between the different brain regions examined within each species. These differences were not due to the fixation.

Secretagogin Immunoreactivity Reveals Lugaro Cells in the Pigeon Cerebellum.

Lugaro cells are inhibitory interneurons found in the upper granular layer of the cerebellar cortex, just below or within the Purkinje cell layer. They are characterized by (1) a fusiform soma oriented in the parasagittal plane, (2) two pairs of dendrites emanating from opposite ends of the soma, (3) innervation from Purkinje cell collaterals, and (4) an axon that projects into the molecular layer akin to granular cell parallel fibers. Lugaro cells have been described in mammals, but not in other vertebrate classes, save one report in teleost fish. Here, we propose the existence of Lugaro cells in the avian cerebellum based on the morphological characteristics and connectivity described above. Immunohistochemical staining against the calcium binding protein secretagogin (SCGN) revealed Lugaro-like cells in the pigeon cerebellum. Some SCGN-labeled cells exhibit fusiform somata and dendrites parallel to the Purkinje cell layer in the parasagittal plane, as well as long axons that project into the molecular layer and travel alongside parallel fibers in the coronal plane. While mammalian Lugaro cells are known to express calretinin, the SCGN-labeled cells in the pigeon do not. SCGN-labeled cells also express glutamic acid decarboxylase, confirming their inhibitory function. Calbindin labeling revealed Purkinje cell terminals surrounding the SCGN-expressing cells. Our results suggest that Lugaro cells are more widespread among vertebrates than previously thought and may be a characteristic of the cerebellum of all vertebrates.

Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494.

Secretagogin (SCGN) has recently been identified to play a crucial role in cell apoptosis, receptor signaling and differentiation. However, its clinical significance and functional roles in SCLC chemoresistance remain unknown. Here we examined the expression of SCGN in clinical samples from SCLC patients and evaluated its relation with clinical prognosis. Then up and down-regulation of SCGN were carried out in SCLC cell lines to assess its influence on chemoresistance. Furthermore, luciferase reporter assay was used to evaluate whether SCGN is a novel direct target of miR-494. Our results revealed that elevated expression of SCGN was correlated with the poorer prognosis of SCLC patients and the more significant correlation with chemosensitivity. We also found that knockdown of SCGN expression in H69AR and H446AR cells increased chemosensitivity via increasing cell apoptosis and cell cycle arrest of G0/G1 phase, while over-expression of SCGN reduced chemosensitivity in sensitive H69 and H446 cells. SCGN as a novel target of miR-494 by luciferase reporter assay, up-regulation of miR-494 can sensitize H69AR cells to chemotherapeutic drugs. These results suggest SCGN is involved in the chemoresistance of SCLC under the regulation of miR-494 and may be a potential biomarker for predicting therapeutic response in treatment SCLC.