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Proteasome inhibition has been observed in many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Here, the effect of proteasome inhibition on the morphology of cultured rat cortical astrocytes was investigated. Increasing evidence suggests that the function of astrocytes is related closely to its morphology. Lactacystin, a specific inhibitor of the 20S proteasome, can induce astrocytes stellation in a dose dependent manner and reorganize the cytoskeleton of astrocytes. Furthermore, decreased levels of expression of Rho A, total Akt, and Phospho-Akt were found in the process of astrocytes stellation and lysophosphatidic acid, an activator of Rho A, can largely reverse the astrocytes stellation caused by lactacystin. This suggests that proteasome inhibition in astrocytes could stabilize signals of morphological changes that might be processed through Rho and Akt signaling cascade. Our results suggest that proteasome inhibition might function as a factor regulating astrocytes morphology in some pathophysiological conditions.

Astrogliosis occurs after brain ischemia, and excessive astrogliosis can devastate the neuronal recovery. Previous reports show that galectin-1 (Gal-1) regulates proliferation of several cell types and plays an important role after nervous system injuries. Here, we found that expression of Gal-1 was remarkably up-regulated in activated astrocytes around ischemic infarct. Furthermore, under ischemic conditions either in vitro or in vivo, Gal-1 was found to inhibit the proliferation of astrocytes in a dose-dependent manner, attenuate astrogliosis and down-regulate the astrogliosis associated expression of nitric oxide synthase and interleukin-1β after the ischemia. All these changes were blocked by lactose, suggesting a lectin dependent manner of Gal-1's function. Moreover, 7-day Gal-1 treatment reduced apoptosis of neurons, decreased brain infarction volume and improved neurological function induced by the ischemia. Together, these findings indicate that through reducing astrogliosis related damages, Gal-1 is a potential therapeutical target for attenuating neuronal damage and promoting recovery of brain ischemia.

Stroke and traumatic injury to the nerve system may trigger axonal destruction and the formation of scar tissue, cystic cavitations and physical gaps. Olfactory ensheathing cells (OECs) can secrete neurotrophic factors to promote neurite growth and thus act as a prime candidate for autologous transplantation. Biological scaffolds can provide a robust delivery vehicle to injured nerve tissue for neural cell transplantation strategies, owing to the porous three-dimensional structures (3D). So transplantation of the purposeful cells seeded scaffolds may be a promising method for nerve tissue repair. This study aimed to evaluate the compatibility of a novel collagen-heparan sulfate biological scaffold with olfactory ensheathing cells in vitro.Collagen-heparan sulfate (CHS) biological scaffolds were made, and then the scaffolds and OECs were co-cultured in vitro. The viability of OECs was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay at days 1, 3, 5 and 7. Statistical analysis was evaluated by student's t test. Significance was accepted at P0.05. OECs were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE), and the CFSE-labeled OECs were seeded into CHS scaffolds. The attachment and growth of OECs in CHS scaffolds were observed and traced directly by fluorescent microscopy and environmental scanning electron microscope (ESEM).CHS biological scaffolds had steady porous 3D structures and no cytotoxicity to OECs (F = 0.14, P = 0.9330). CHS biological scaffolds were good bridging materials for OECs attachment and proliferation, and they promoted the axonal growth.The compatibility of CHS biological scaffolds with OECs is pretty good and CHS biological scaffold is a promising cell carrier for the implantation of OECs in nerve tissue bioengineering.

Increasing evidence indicates that proteasome inhibition occurs in multiple central nervous system (CNS) disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Compared with the extensive studies on neurons, little attention is paid on the proteasome inhibition in astrocytes. Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in cultured astrocytes. Simultaneously, lactacystin suppressed the expression of cell cycle proteins in astrocytes and caused the proliferating astrocytes arrested at G1/S checkpoint. Western blots showed that proteasome inhibition led to a decrease in cdk-2, cdk-4, cyclin D1 expression accompanied with an increase in p21waf1/cip1 expression. The effect of chronic low-level proteasome inhibition on astrocytes was consistent with that in acute proteasome inhibition. Furthermore, increased levels of interleukin-6 (IL-6) secretion, STAT-3 and phospho-STAT-3 expression were found, suggesting that proteasome inhibition in astrocytes could stabilize signals of grow arrest through the JAK/STAT signaling cascade.