Age dependent learning and memory deficit in Pentylenetetrazol kindled mice.

Epilepsy is a chronic neurological disorder and well documented to induce cognitive impairment. Further onset of epilepsy at different age levels have different effect on cognitive function. Kindling has been used to model clinical epilepsy to study different psychiatric and neurological changes associated with it. Only one study has been reported for age dependent learning deficit in kindled rats but till date no such study is available for mice. Therefore this study was envisaged to find out the correlation of age of mice with feasibility for induction and resistance to kindling and learning and memory deficits. In this study, kindling was induced by administration of subconvulsive dose of pentylenetetrazol (35 mg/kg; i.p.) on alternate days in mice of different age group (2, 6 and 12 month old). For the evaluation of short term, long term spatial and contextual fear memory Elevated Plus Maze and Passive Shock Avoidance Paradigm were used respectively. Induction of kindling significantly impaired learning and memory in different age group of mice as compared to their naïve. Kindling also affected the working and reference spatial memory, with function of age in kindled mice, and contextual fear memory in kindled mice, however not in age dependent manner. Thus the present study validated the existence of age dependent differences in learning and memory deficit and induction of kindling in mice. Results suggested suitability of 6 month old mice for long term neuropharmacological studies pertaining to epilepsy associated cognitive deficit with adequate memory deficit and insignificant resistance to kindling and mortality.

Mishra A ，Goel RK 《-》

Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice.

Epilepsy is a chronic neurological disorder and generally associated with certain psychiatric comorbidities. Among several comorbidities depressive behavior and cognitive impairment has been reported to be most debilitating comorbidity associated with epilepsy. This study was envisaged to evaluate the ameliorative effect of Curcumin on depression like behavior and cognitive impairment observed in pentylenetetrazole kindled animals. Male Swiss Albino mice were kindled with subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.). Successfully kindled animals were used in the study to observe the effect of different treatments. Treatment groups received phenytoin (30 mg/kg) and Curcumin (50, 100 and 200mg/kg) for 15 days. The animals were challenged with pentylenetetrazole (35 mg/kg, i.p.) on day 5, 10 and 15 and seizure severity score, immobility period, number of mistakes and step down latency were recorded. On 15th day, all the animals were sacrificed after behavioral evaluations and their brain was isolated and homogenized to estimate brain norepinephrine, serotonin, total nitrite level and acetylcholinesterase activity. Phenytoin treatment significantly improved the depressive like behavior along with its anticonvulsant effect, however was unable to improve memory impairment. Curcumin significantly attenuated seizure severity, depression like behavior and memory impairment in kindled animals, in dose dependent manner. These results were supported by the biochemical modulation of brain monoamine, nitrosative stress level and acetylcholinesterase activity. Thus present study concluded that Curcumin has the ameliorative effect on seizure severity, depression like behavior and memory impairment in pentylenetetrazole kindled mice, possibly via central monoaminergic modulation and inhibitory effect on nitrosative stress and acetylcholinesterase activity.

Choudhary KM ，Mishra A ，Poroikov VV ，Goel RK ... -  《-》

Effect of prenatal pentylenetetrazol-induced kindling on learning and memory of male offspring.

Current data concerning the effects of maternal seizure during pregnancy on newborns are limited. This study was carried out to investigate the effect of prenatal pentylenetetrazol (PTZ)-induced kindling on learning and memory of offspring. Female Wistar rats were kindled with i.p. injections of 25 mg/kg of PTZ on day 13 of their pregnancy. The spatial performance and passive avoidance learning of pups were tested at 7 weeks and 12 weeks of age using Morris water maze (MWM) task and shuttle-box apparatus, respectively. We found, for the first time, that prenatal exposure to maternal seizure induced by PTZ leads to a significant impairment of learning and memory. In addition, the number of live birth was significantly lower in kindled rats compared to control. In MWM studies, the young offspring of kindled rats had poor spatial learning ability. The frequent tonic-clonic seizures in pregnancy was also associated with a poor memory as evidenced by decrease in distance swam in the target quadrant by the offspring of the kindled mother in the adulthood. Data obtained from shuttle-box studies showed that retention latencies of pups born to kindled dams were significantly reduced compared to those born to control dams. The hippocampus, amygdala and frontal cortex are very important for memory consolidation and our data suggest that subsequent developmental events are not sufficient to overcome the adverse effects of prenatal exposure to maternal seizures to these regions of the brain. These observations may have clinical implications for cognitive and memory dysfunction associated with epilepsy during pregnancy.

Pourmotabbed A ，Nedaei SE ，Cheraghi M ，Moradian S ，Touhidi A ，Aeinfar M ，Seyfi Z ，Pourmotabbed T ... -  《-》

Adjuvant anticholinesterase therapy for the management of epilepsy-induced memory deficit: a critical pre-clinical study.

Epilepsy is one of the major neurological disorders still awaiting safer drugs with improved antiepileptic effect and lesser side effects. Apart from epilepsy itself, AEDs also have been shown to induce cognitive impairment in patients with epilepsy. There are limited data for the treatment of this menace. As cholinergic approach has widely been practiced for the restoration of memory in various neurodegenerative disorders, this study was envisaged to evaluate add on effect of acetylcholinesterase inhibitor (tacrine) with phenytoin in pentylenetetrazole-kindling-induced learning and memory deficit in mice. In this study, mice were kindled using subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.; at interval of 48 ± 2 hr) and successfully kindled animals were divided into different groups and treated with vehicle, phenytoin and phenytoinin in combination with tacrine (0.3 mg/kg), atropine (1 mg/kg) and tacrine + atropine. Effect of different interventions on learning and memory was evaluated using elevated plus maze and passive shock avoidance on days 5, 10, 15 and 20. Phenytoin-treated kindled animals were associated with learning and memory deficit, while tacrine supplementation improved memory deficit with increased seizure severity score. Atropine treatment significantly reversed the protective effect of tacrine. Neurochemical findings also support the behavioural finding of the study. Our results suggest the use of anticholinesterases, with better seizure tolerance, for the management of cognitive impairment of epilepsy, as adjunct therapy.

Mishra A ，Goel RK 《-》

[Impaired memory following repeated pentylenetetrazol treatments in kindled mice].

Takechi K ，Suemaru K ，Kawasaki H ，Araki H ... -  《-》