A specific protein abnormality associated with cobalt-induced epilepsy in mice

Density profiles of protein patterns from cortical tissue exhibit an increase in only one peak when mice are rendered epileptic by application of cobalt to the cortex. The increase and diminution in peak height, attributed to a change in the concentration of a single protein (protein 3), coincides with the severity of seizure activity; with the degree of abnormality of the cortex region affected; and with the time of onset, duration, and disappearance of the epileptic condition. Thus, the concentration of protein 3 is highest in tissue from the site of cobalt application (up to 10× normal), is increased less in the focus (up to 5× normal), while in the mirror focus (contralateral, not exposed surgically), the increase in the concentration of protein 3 is still detectable, but not as pronounced. The concentrations in these cortex regions decrease to normal in reverse order to their elevation when the epileptic signs begin to diminish. Furthermore, the increase of protein 3 in all three areas is proportional to the severity of epilepsy. The concentration of protein 3 also becomes enhanced when the cortex is injured, but no progressive increase in the concentration occurs with time, nor does the concentration reach that observed in the site of cobalt application or the focal region. These mice do not exhibit spontaneous seizures, but injection of pentelynetetrazol confirms that animals with brain injury only are more susceptible to seizures. The results of this study suggest that both the area of cortex affected and the intensity of metabolic alterations may be precipitating factors in establishing an epileptic condition. This view is in agreement with clinical observations on epilepsy.