Expression of Adenomatous Polyposis Coli Protein in Reactive Astrocytes in Hippocampus of Kainic Acid-Induced Rat

Abstract

The adenomatous polyposis coli gene (APC) was initially identified through its link to colon cancer. It is associated with the regulation of cell cycle progression, survival, and differentiation of normal tissues. Recent studies have demonstrated that APC is also expressed in the adult brain at high levels. However, its role in glial cells under pathological progression remains unclear. In this study, we evaluated the expression of APC and its association with beta-catenin signaling pathway, following the induction of an excitotoxic lesion by kainic acid (KA) injection, which cause pyramidal cell degeneration. APC was predominantly present in oligodendrocytes in the normal brain, but was specifically associated with activated astrocytes in the KA-treated brain. Our quantitative analysis revealed that APC significantly increased from 1 day post lesion (PI), reached peak values at 3 days PI, and decreased thereafter. The phospho-GSK3beta levels also showed similar spatiotemporal patterns while beta-catenin expression was reduced at 1 and then increasingly returned to normal levels at 3, 7 days PI. For the first time, our data demonstrate the injury-induced astrocytic changes in the levels of APC, GSK3beta, and beta-catenin in vivo, which may actively be participate in cell adhesion and in the signaling pathway regulating cell survivals during brain insults.

Astrocyte-targeted production of interleukin-6 reduces astroglial and microglial activation in the cuprizone demyelination model: Implications for myelin clearance and oligodendrocyte maturation

“…5I). Some studies suggested that in certain pathological conditions, in addition to OLs, activated astrocytes might express APC (Lee et al, 2010;Leroy et al, 2001). To address this issue, we performed double immunofluorescent labeling for APC/GFAP.…”

Wnt1, FoxO3a, and NF-κB oversee microglial integrity and activation during oxidant stress

“…In general, Wnt proteins serve a variety of cellular functions that include the proliferation and enhancement of cellular survival [12, 16, 32, 34, 35]. Wnt signaling pathways also have been described in astrocytic cells [36], but the function that Wnt1 plays during microglial survival and proliferation remains unclear. During periods of cell injury, Wnt signaling can be depressed in bone tissue during ethanol-induced oxidative stress [37], in endothelial cells during elevated glucose [19], and in neurons during β-amyloid toxicity [20].…”

Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines

“…The hilar neurons are sensitive to KA-induced neurotoxicity, but neuron loss in the other areas of the hippocampus differs between animal species and strains [38-40]. In rats, the systemic injections of KA produced widespread neuronal death, primarily in the hippocampus hilus, CA1 and CA3 areas [30, 41]. Mouse strains vary significantly in their sensitivity to KA-induced neurodegeneration [39, 40, 42, 43].…”