Abstract

(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distress epilepsy-related behavioral and biochemical outcomes are associated with cognition and emotion. (2) Methods: Young and middle-aged Wistar rats (3 or 12 months old) were treated with pentylenetetrazol (PTZ, 35 mg/kg) and injected on alternated days for 20 (young rats) and 32 days (middle-aged rats). Kindling was reached after two consecutive stages 4 plus one stage 5 or 6 in Racine scale. Control and kindled rats were evaluated in the elevated plus-maze (EPM) and object-recognition tests and their hippocampus was collected 24 h later for mitogen-activated protein kinases (MAPK) dosage. (3) Results: Middle-aged rats presented a higher resistance to develop kindling, with a decrease in the seizure severity index observed following the 4th and 9th PTZ injections. Middle-aged rats displayed an increased duration of the first myoclonic seizure and an increased latency to the first generalized seizure when compared to younger rats. The induction of kindling did not impair the animals’ performance (regardless of age) in the object-recognition task and the EPM test as well as it did not alter the hippocampal levels of MAPKs. (4) Significance: Our findings reveal that, despite age-related differences during epileptogenesis, middle-aged rats evaluated after kindling performed similarly during discriminative learning and emotional tasks in comparison to young animals, with no alteration of hippocampal MAPKs. Additional investigation must be carried out to explore the electrophysiological mechanisms underlying these responses, as well as the long-term effects displayed after kindling.

Highlights

  • Epilepsy is characterized by a persistent brain susceptibility to unprovoked seizures, occurring after at least one epileptic seizure [1]

  • The induction of kindling did not impair the animals’ performance in the object-recognition task and the elevated plus-maze (EPM) test as well as it did not alter the hippocampal levels of mitogen-activated protein kinases (MAPK). (4) Significance: Our findings reveal that, despite age-related differences during epileptogenesis, middle-aged rats evaluated after kindling performed during discriminative learning and emotional tasks in comparison to young animals, with no alteration of hippocampal

  • We investigated whether and how aging may alter epilepsy-related behavior and hippocampal biochemical outcomes associated with learning, memory, and emotionality in middle-aged rats following a kindling protocol induced by the systemic injection of PTZ

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Summary

Introduction

Epilepsy is characterized by a persistent brain susceptibility to unprovoked seizures, occurring after at least one epileptic seizure [1] This chronic disorder affects approximately 50 million people worldwide, deeply disturbing their quality of life, with an occurrence of about 48 per 100,000 cases per year in the United States [2]. Little is known regarding the neurobiological and clinical aspects, the cognitive and emotional responses, displayed by people with late-onset epilepsy [3]. Such unpredictable scenarios impact preventive and therapeutic strategies that could significantly improve the prognosis in these unwell investigated patients [3]. Specific features between young and aged brain function facing epileptogenesis in animal models may shed light into the mechanisms underlying this uncharted phenomenon and potentially translate to preventive and substitute therapeutic approaches [4]

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