Aβ Upregulates and Colocalizes with LGI3 in Cultured Rat Astrocytes

Abstract

1. The leucine-rich glioma inactivated (LGI) family of genes encodes a leucine-rich repeat (LRR) protein, proteins that are thought to be specifically involved in protein-protein and protein-matrix interactions. Since amyloid beta peptide (Abeta) has been previously shown to induce the expression of another LRR-encoding gene in neural cells, we assessed how Abeta affects LGI gene expression in rat primary cerebral cortical cultures and astrocyte cultures. Both RT-PCR and Western Blotting analyses revealed that Abeta robustly induced the expression of LGI3 in rat astrocyte cultures.2. Western Blotting analyses also showed that both glial fibrillary acidic protein (GFAP) and apolipoprotein E (ApoE) significantly increased coincidentally with the Abeta-induced upregulation of LGI3. Immunocytochemistry showed that LGI3 colocalized with Abeta at plasma membranes and also with internalized Abeta in astrocytes. These findings suggest that activated LGI3 may be involved in the astroglial response against Abeta.

The difference in gliosis induced by β-amyloid and Tau treatments in astrocyte cultures derived from senescence accelerated and normal mouse strains

“…2). This is consistent with the result of Kimura et al (2007) that after 24 h of incubation, the increase in GFAP was not significant. However, it should note that Kimura et al used Fischer 344 rats, which is a normal strain of laboratory rat (Holmes 2003).…”

“…2), suggesting that astrogliosis induced by Ab might be a prominent event in aging prone astrocytes, while it might be an early or inconspicuous event in normal astrocytes ( Fig. 4 in Kimura et al 2007). In fact, in untreated control cultures, the GFAP level of P8 astrocytes was slightly higher than that of R1 astrocytes (Fig.…”

“…The responses of astrocytes against Ab occur even before obvious neuronal damage can be detected suggesting that the role of astrocytes during the early stages of AD pathology must be very important (Kimura et al 2004(Kimura et al , 2007. In fact, GFAP was significantly increased with the Ab treatment of astrocyte in culture (Kimura et al 2007). Also, GFAP mRNA showed a 18-fold increase in astrocytes surrounding b-amyloid plaque indicating the induction of gliosis by Ab (Burbach et al 2004).…”

“…Furthermore, studies have shown that astrocytes play an important role in clearing Ab from the brain (Matsunaga et al 2003;Wyss-Coray et al 2003). The responses of astrocytes against Ab occur even before obvious neuronal damage can be detected suggesting that the role of astrocytes during the early stages of AD pathology must be very important (Kimura et al 2004(Kimura et al , 2007. In fact, GFAP was significantly increased with the Ab treatment of astrocyte in culture (Kimura et al 2007).…”

Immunohistochemical and Biochemical Analyses of LGI3 in Monkey Brain: LGI3 Accumulates in Aged Monkey Brains

“…A recent study showed that Ab induces the expression of a transmembrane protein that contains leucine-rich repeats (LRRs) (Satoh et al 2002). Using cultured rat astrocytes, we recently showed that Ab upregulates and colocalizes with leucine-rich glioma inactivated (LGI) 3, a transmembrane protein containing LRRs (Kimura et al 2007). …”