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Effect of phenytoin on cytoskeletal protein phosphorylation and neuronal structure in the rat sensory cortex
G Ruiz1, O G Flores, R González-Plaza
1Department of Cell Biology, Catholic University of Chile, Santiago.
Insights
Phenytoin (PH) alters brain neuron structure by changing the phosphorylation of cytoskeletal proteins like actin. This anticonvulsant
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Phenytoin (PH) is an anticonvulsant with known side effects, including morphological changes in brain cortex neurons.
- Evidence suggests PH may affect neuronal function by altering protein phosphorylation patterns.
- Cytoskeletal proteins are crucial for neuronal structure, making their phosphorylation a potential target of PH action.
Purpose of the Study:
- To investigate the effects of Phenytoin (PH) on the phosphorylation of cytoskeletal proteins in the brain.
- To determine if PH-induced changes in cytoskeletal protein phosphorylation correlate with observed morphological alterations in neurons.
Main Methods:
- Studied the impact of PH on brain cytoskeletal protein phosphorylation in 30-day-old rats.
- Utilized in vitro labeling experiments with [32P] to quantify changes in protein phosphorylation.
- Identified a 43-kDa polypeptide as actin using novel in vitro methods.
Main Results:
- Phenytoin (PH) administration altered the phosphorylation patterns of cytoskeletal proteins in rat brain extracts.
- A decrease in [32P] labeling was observed for a 43-kDa polypeptide (identified as actin).
- Increases in [32P] labeling were noted for 38-kDa and 120-kDa polypeptides.
Conclusions:
- Phenytoin (PH) affects the posttranslational phosphorylation of actin and other cytoskeletal proteins.
- These PH-induced alterations in protein phosphorylation may underlie the observed changes in dendritic patterns within the somatosensory cortex.
Abstract:
Phenytoin (PH) is commonly used as an anticonvulsant drug, and it causes several collateral effects including morphological changes in brain cortex neurons and teratogenic lesions in infants of epileptic mothers. Several lines of evidence indicate that PH may exert its action through the modification of phosphorylation patterns of neuronal polypeptides. We have studied the effects of PH on the phosphorylation of cytoskeletal proteins, because this could be related to the structural modifications induced by PH administration. The dendritic pattern of deep layers of the somatosensory cortex is clearly modified by PH but not the cell number, indicating that the drug disturbs the architecture of the neurons examined. In fact, the pattern of phosphorylation in cytoskeletal extracts of brains of 30-day-old rats is changed by PH. In vitro labeling experiments show decrease in the [32P] level of a 43-kDa polypeptide, whereas 38- and 120-kDa polypeptides show increases in their [32P] contents. The 43-kDa polypeptide has been identified as actin by in vitro experiments using a novel approach to determine cytoskeletal polypeptide behavior. We conclude that PH affects the posttranslational phosphorylation of actin and other related cytoskeletal proteins and in this manner may alter the normal morphological layout of dendritic patterns in the somatosensory cortex.