Anat Cell Biol.  2010 Jun;43(2):150-156. 10.5115/acb.2010.43.2.150.

Phosphorylation of 14-3-3zeta at serine 58 and neurodegeneration following kainic acid-induced excitotoxicity

• Jeong EA
• Jeon BT
• Kim JB
• Kim JS
• Cho YW
• Lee DH
• Kim HJ
• Kang SS
• Cho GJ
• Choi WS
• Roh GS

• KMID: 2168888
• DOI: http://doi.org/10.5115/acb.2010.43.2.150

Abstract

Oxidative stress-induced cell death leads to phosphorylation of 14-3-3zeta at serine 58. 14-3-3zeta is detected at significant levels in cerebrospinal fluid after kainic acid (KA)-induced seizures. Here we examined temporal changes in 14-3-3zeta phosphorylation in the hippocampus and amygdala of mice after KA treatment. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. We observed an increase in TUNEL and Fluoro-Jade B (FJB)-stained neurons in the hippocampus and amygdala of KA-treated mice. Phospho (p)-14-3-3zeta and p-JNK expression was increased in the hippocampus 2 and 6 h after KA treatment, respectively. In immunohistochemical analysis, p-14-3-3zeta-positive cells were present in the CA3 region of the hippocampus and the central nucleus of amygdala (CeA) of KA-treated mice. Thus, phosphorylation of 14-3-3zeta at serine 58 may play an important role in KA-induced hippocampal and amygdaloid neuronal damage.

Keyword

Kainic acid; 14-3-3zeta; hippocampus; amygdala; neurodegeneration

MeSH Terms

Amygdala
Animals
Cell Death
Fluoresceins
Hippocampus
In Situ Nick-End Labeling
Kainic Acid
Mice
Neurons
Phosphorylation
Seizures
Serine
Fluoresceins
Kainic Acid
Serine

Figure

• 

  Fig. 1 Effect of KA treatment on neuronal death and neurodegeneration in the hippocampus and amygdala. (A) Location of hippocampal cell death in a coronal brain section 48 h after KA treatment. (CA3, Cornu ammonis 3 of the hippocampus; CeA, Central nucleus of the amygdala; BLA, Basolateral nucleus of the amygdala). (B) Photo-micrograph of TUNEL and FJB-stained cells in the CA3 region of the hippocampus, CeA, and BLA 48 h after KA treatment. Scale bars = 200 µm.

• 

  Fig. 2 Effect of KA treatment on p-JNK expression in the hippocampus and amygdala. Western blot showing the time course of p-JNK expression in the hippocampus (A) and amygdala (B) after KA treatment. p-JNK was normalized to α-tubulin and represented as arbitrary units. Data are presented as the mean±SEM. *indicates P<0.05.

• 

  Fig. 3 Effect of KA treatment on p-14-3-3ζ expression in the hippocampus. (A) Representative micrographs showing p-14-3-3ζ immunoreactivity in mouse hippocampus after KA treatment. (B) Western blot showing the time course of p-14-3-3ζ and total 14-3-3ζ expression in the hippocampus after KA treatment. (C) p-14-3-3ζ was normalized to 14-3-3ζ and represented as ratio. Data are presented as the mean±SEM. *indicates P<0.05. Scale bar = 100 µm. Arrows indicate p-14-3-3ζ-immunostained cells from CA3 region of the hippocampus.

• 

  Fig. 4 Effect of KA treatment on p-14-3-3ζ expression in the amygdala. (A) Representative micrographs showing p-14-3-3ζ immunoreactivity in the CeA after KA treatment. (B) Western blot showing the time course of p-14-3-3ζ and total 14-3-3ζ expression in the hippocampus after KA treatment. (C) p-14-3-3ζ was normalized to 14-3-3ζ and represented as a ratio. Data are presented as the mean±SEM. *indicates P<0.05. Scale bar=100 µm.

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