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Assessment of Memory Function in Pilocarpine-induced Epileptic Mice
Published on: June 4, 2020
The Na+/K+ATPase activity is increased in the hippocampus after multiple status epilepticus induced by pilocarpine in
Erika Reime Kinjo1, Ricardo Mario Arida, Daniela Mara de Oliveira
1Depto. de Neurologia e Neurocirurgia, Disciplina de Neurologia Experimental, Universidade Federal de São Paulo, Unifesp. Rua Botucatu, 862 - Edif. Leal Prado, CEP 04023-900, São Paulo, Brazil.
Insights
Repetitive pilocarpine-induced status epilepticus (SE) in developing rats increases hippocampal Na(+)/K(+)ATPase activity long-term. A single SE episode had no effect, but multiple SE events induced lasting hyperactivity, indicating potential brain damage.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- Na(+)/K(+)ATPase is crucial for maintaining neuronal excitability.
- Enzyme malfunction is linked to neuronal hyperexcitability.
- Pilocarpine-induced status epilepticus (SE) in developing rats causes hyperexcitability and brain damage.
Purpose of the Study:
- To investigate the long-term effects of single versus repetitive pilocarpine-induced SE on hippocampal Na(+)/K(+)ATPase activity in developing rats.
- To understand the enzyme's role in SE-induced neuronal hyperexcitability during development.
Main Methods:
- Developing rats were subjected to one or three pilocarpine-induced SE episodes on specific postnatal days.
- Hippocampal Na(+)/K(+)ATPase activity was measured 7 and 30 days post-SE (at P16 and P39).
- Activity levels were compared between SE-exposed groups and control rats.
Main Results:
- A single SE episode did not alter Na(+)/K(+)ATPase activity at P16 or P39.
- Three consecutive SE episodes significantly increased hippocampal Na(+)/K(+)ATPase activity by +142% at P16 and +400% at P39.
- Control rats showed a significant reduction in Na(+)/K(+)ATPase activity at P39 compared to P16.
Conclusions:
- Multiple pilocarpine-induced SE events in developing rats lead to a sustained increase in hippocampal Na(+)/K(+)ATPase activity.
- This long-lasting hyperactivity suggests a persistent state of neuronal hyperexcitability.
- The findings highlight the detrimental impact of repeated seizures on developing brain enzyme function.
Abstract:
The effects of repetitive pilocarpine-induced status epilepticus (SE) in the hippocampal Na(+)/K(+)ATPase activity were studied in developing rat. Na(+)/K(+)ATPase is a membrane-bound enzyme responsible for the active transport of sodium and potassium ions through the membrane. It is necessary to maintain neuronal excitability. The malfunction of this enzyme has been associated with neuronal hyperexcitability. The pilocarpine-induced status epilepticus in developing rats leads to neuronal hyperexcitability and brain damage. We examined the activity of the Na(+)/K(+)ATPase enzyme in hippocampus of rats submitted to 1 episode of status epilepticus on postnatal day 9 and to 3 episodes of pilocarpine-induced status epilepticus on postnatal days 7, 8 and 9. Our findings showed that one status epilepticus episode does not modify the Na(+)/K(+)ATPase activity in hippocampus of rats studied 7 or 30 days later (at P16 or P39). However, an increase in the Na(+)/K(+)ATPase activity was detected in hippocampus of rats submitted to three consecutive status epilepticus during the development studied 7 (+142%) and 30 (+400%) days following the injections. In addition, a significant reduction in the Na(+)/K(+)ATPase activity was observed in control rats at P39 compared to P16. Our data suggest that multiple pilocarpine-induced status epilepticus in developing rats induce long-lasting increase in the Na(+)/K(+)ATPase activity in the hippocampus, reflecting hyperexcitability.

