Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes.

Abstract

Seizures may exert pathophysiological effects on dendritic spines, but the molecular mechanisms mediating these effects are poorly understood. Actin represents a major structural protein of dendritic spines, and actin filaments (F-actin) can be depolymerized by the regulatory molecule, cofilin, leading to structural or functional changes in spines in response to normal physiological activity. To investigate mechanisms by which pathophysiological stimuli may affect dendritic spine structure and function, we examined changes in F-actin and cofilin in hippocampus due to 4-aminopyridine (4-AP)-induced seizures/epileptiform activity in vivo and in vitro and investigated possible structural correlates of these changes in actin dynamics. Within an hour of induction, seizure activity caused both a significant decrease in F-actin labeling, indicating depolymerization of F-actin, and a corresponding decrease in phosphorylated cofilin, signifying an increase in cofilin activity. However, 4-AP seizures had no overt short-term structural effects on dendritic spine density. By comparison, high potassium caused a more dramatic decrease in cofilin and an immediate dendritic beading and loss of dendritic spines. These findings indicate that activation of cofilin and depolymerization of F-actin represent mechanisms by which seizures may exert pathophysiological modulation of dendritic spines. In addition to affecting non-structural functions of spines, the degree to which overt structural changes occur with actin depolymerization is dependent on the severity and type of the pathophysiological stimulus.

• Authors: Yannan Ouyang, Xiao-Feng Yang, Xiao Yan Hu, Ebru Erbayat-Altay, Ling-Hui Zeng, Jin-Moo Lee, Michael Wong
• Journal: Brain research (Brain Res) Vol. 1143 Pg. 238-46 (Apr 27 2007) ISSN: 0006-8993 [Print] Netherlands
• PMID: 17320053 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Actin Depolymerizing Factors
• Green Fluorescent Proteins
• 4-Aminopyridine
• Potassium

Topics

• 4-Aminopyridine
• Actin Cytoskeleton (metabolism)
• Actin Depolymerizing Factors (metabolism)
• Animals
• Dendritic Spines (metabolism)
• Disease Models, Animal
• Electroencephalography (methods)
• Enzyme Activation (drug effects)
• Gene Expression Regulation (drug effects)
• Green Fluorescent Proteins (metabolism)
• Hippocampus (drug effects, pathology)
• In Vitro Techniques
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neurons (drug effects, metabolism, pathology)
• Potassium (pharmacology)
• Seizures (chemically induced, pathology, physiopathology)