cyclin-d1 and Seizures

The effects of chloroquine on glial fibrillary acidic protein (GFAP), proliferation cell nuclear antigen (PCNA) and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole (PTZ) were observed in the present study. Forty-eight male adult Sprague-Dawley (SD) rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram (EEG) were observed and recorded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group (IV - V degree), and slight seizure activity (I - IIl degree) in the chloroquine intervening group (P < 0.05). EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low-amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group (P < 0.05 and P < 0.01, respectively). No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups (P > 0.05). The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups (P < 0.05). Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.

Topics: Animals; Cerebral Cortex; Chloroquine; Cyclin D1; Glial Fibrillary Acidic Protein; Hippocampus; Male; Pentylenetetrazole; Proliferating Cell Nuclear Antigen; Random Allocation; Rats; Rats, Sprague-Dawley; Seizures

Citron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-K-/- mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS.

Topics: Animals; Apoptosis; Ataxia; Brain; Cell Division; Cyclin D1; DNA; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Neurodegenerative Diseases; Neurons; Polyploidy; Protein Serine-Threonine Kinases; rho-Associated Kinases; Seizures; Stem Cells