Impairments in cognitive functions and emotional and social behaviors in a rat lithium-pilocarpine model of temporal lobe epilepsy

Smolensky, Ilya V.; Зубарева, О. Е.; Kalemenev, S. V.; Lavrentyeva, Valeria V.; Dyomina, A. V.; Karepanov, Anton A.; Zaitsev, Aleksey V.

doi:10.1016/j.bbr.2019.112044

Cited by 40 publications

(36 citation statements)

References 66 publications

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“…Thereby, the increased time spent in aversive areas of the elevated-plus maze might be related to an overall increased activity and reduced risk assessment. An increase in activity patterns has previously also been reported in different post-status epilepticus models [26][27][28]. Hyperactivity in these animals models with repeated seizure induction reflects the increased prevalence for attention-deficit/hyperactivity disorder in pediatric and adult patients with epilepsy [29,30].…”

Section: Discussionsupporting

confidence: 54%

Toward evidence-based severity assessment in mouse models with repeated seizures: I. Electrical kindling

Boldt

Koska

Dijk

et al. 2021

Epilepsy & Behavior

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Objective: Ethical decisions about an allowance for animal experiments need to be based on scientifically sound information about the burden and distress associated with the experimental procedure and models. Thereby, species differences need to be considered for recommendations regarding evidence-based severity assessment and refinement measures. Methods: A comprehensive analysis of behavioral patterns and corticosterone or its metabolites in serum and feces was completed in kindled mice. The impact of kindling via two different stimulation sites in the amygdala and hippocampus was determined. Data were compared to those from naive and electrodeimplanted groups. Results: Amygdala and hippocampus kindled mice exhibited comparable behavioral patterns with increased activity in the open field, reduced anxiety-associated behavior in the elevated-plus maze, and increased anhedonia-associated behavior in the saccharin preference test. In addition, repeated stimulation of the hippocampus caused a reduction in burrowing behavior and an increase in active social interaction. Levels of corticosterone and its metabolites were not altered in serum or feces, respectively. A comparison of mouse data with findings from amygdala kindled rats confirmed pronounced species differences in behavioral patterns associated with the kindling process. Significance: Taken together the findings suggest a severity classification for the mouse kindling paradigms as moderate regardless of the stimulation site. The outcome of the species comparison provides valuable guidance for species selection for studies exploring behavioral comorbidities. In this context, it is emphasized that the mouse kindling paradigms seem to be well suited for studies exploring the link between ictal events and network alterations on the one hand, and hyperactivity and anhedoniaassociated behavior on the other hand. Moreover, the underlying pathophysiological mechanisms and the impact of therapeutic interventions on these behavioral alterations can be studied in these paradigms providing guidance for the clinical management of respective psychiatric comorbidities in patients.

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Section: Discussionsupporting

confidence: 54%

Toward evidence-based severity assessment in mouse models with repeated seizures: I. Electrical kindling

Boldt

Koska

Dijk

et al. 2021

Epilepsy & Behavior

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“…As we mentioned before, the postsynaptic alterations in glutamate receptors and signaling pathways could impede PS-LTP generation under EPI conditions, and therefore, LEV may not have had an effect. Otherwise, our PS-LTP data could explain previous reports with respect to the cognitive impairment presented in animal models and patients with TLE [ 80 , 81 , 82 ], as it has been postulated that the LTP corresponds to the cellular bases of memory processes. Although our results do not show positive effects on short-term plasticity and PS-LTP in rats treated with LEV, it cannot be overlooked that the drug may enhance cognitive processes in the long term, as was observed in a study conducted in children who were treated with LEV for benign epilepsy and showed an improvement in cognitive abilities [ 83 ].…”

Section: Discussionsupporting

confidence: 82%

Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy

et al. 2020

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Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

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“…Rats were placed into a round arena with a diameter of 1 m, the height of the wall of 30 cm, and a lightness of 8 Lx. Rat movements were video recorded, and tracks were analyzed software "Round and Cross" (Institute of Experimental Medicine, St. Petersburg, Russia) [60]. Distance traveled during 3 min of testing was used to estimate the locomotor activity and time spent in the center of the arena ( 1 /4 of the arena's radius) and thigmotaxis (less than 7 cm from the wall) for estimation of the anxiety level.…”

Section: Behavioral Testsmentioning

confidence: 99%

Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats

Postnikova

Malkin

Захарова

et al. 2021

IJMS

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Disrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investigated the consequences of ceftriaxone (CTX), an enhancer of glutamate transporter 1 expression, treatment on long-term synaptic potentiation (LTP) in the hippocampus of young rats. In this study, 5-day administration of CTX (200 mg/kg) significantly weakened LTP in CA3-CA1 synapses. As shown by electrophysiological recordings, LTP attenuation was associated with weakening of N-Methyl-D-aspartate receptor (NMDAR)-dependent signaling in synapses. However, PCR analysis did not show downregulation of NMDAR subunits or changes in the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. We assume that extracellular burst stimulation activates fewer synapses in CTX-treated animals because increased glutamate reuptake results in reduced spillover, and neighboring synapses do not participate in neurotransmission. Attenuation of LTP was not accompanied by noticeable behavioral changes in the CTX group, with no behavioral abnormalities observed in the open field test or Morris water maze test. Thus, our experiments show that increased glutamate clearance can impair long-term synaptic plasticity and that this phenomenon can be considered a potential side effect of CTX treatment.

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Impairments in cognitive functions and emotional and social behaviors in a rat lithium-pilocarpine model of temporal lobe epilepsy

Cited by 40 publications

References 66 publications

Toward evidence-based severity assessment in mouse models with repeated seizures: I. Electrical kindling

Toward evidence-based severity assessment in mouse models with repeated seizures: I. Electrical kindling

Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy

Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats

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