Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats)

Sitnikova, Evgenia

doi:10.3390/biomedicines12010122

Cited by 3 publications

(1 citation statement)

References 115 publications

(235 reference statements)

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“…The WAG/Rij rat absence epilepsy model is a suitable model for studying the development of epilepsy and comorbidities. WAG/Rij rats exhibit depression-like behavior compared to nonepileptic Wistar rats ( Sarkisova et al, 2003 ; Sarkisova and van Luijtelaar, 2022 ; Sitnikova, 2024 ). Around 3 months, when SWDs become more evident, depression-like behavioral symptoms also emerge.…”

Section: Discussionmentioning

confidence: 96%

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy

Balikci,

Eryilmaz,

Guler

et al. 2024

Front. Behav. Neurosci.

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Investigations in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats that are susceptible to genetic absence epilepsy have demonstrated that environmental modifications affect absence seizures. Previously, we showed that neonatal tactile stimulations produce disease-modifying effect on genetically determined absence epilepsy and associated depression in Wag/Rij rats. The study presented here examined the effect of TS during late ontogenesis (adolescence and young adulthood) on epilepsy and depression outcomes in this genetically epileptic rat strain. On postnatal day (PND) 38, male WAG/Rij rats randomly were assigned to either the tactile stimulation (TS), handled or control group (unhandled) with 8 animals in each group. Following a 7-day adaptation period to their new surroundings, the animals were submitted to tactile stimulation from PND 45 to PND 90, five days per week, for 5 min daily. The tactile-stimulated rat was removed from its cage, placed on the experimenter’s lap, and had its neck and back gently stroked by the researcher. The handled rats were taken to another cage and left alone for 5 min daily from PND 45 to PND 90. The control rats were left undisturbed in their home cage, except for regular cage cleaning. After PND 90, all rats were left undisturbed until behavioral testing and EEG recording. When the animals were 7 months old, they were subjected to the sucrose consumption test (SCT) and the forced swimming test (FST). Electroencephalogram (EEG) recordings were made at 8 months of age in order to measure electroencephalographic seizure activity, thus, the spike–wave discharges (SWDs). Tactile-stimulated rats showed increased sucrose consumption and number of approaches to the sucrose solution in the SCT when compared with the handled and control rats. In the FST, rats in TS group showed lower immobility time and greater immobility latency, active swimming time and diving frequency than the handled and control rats. The duration and the number of seizures were not different amongst the groups. The data obtained suggest that TS in young rats is able to prevent depression in WAG/Rij rats.

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Section: Discussionmentioning

confidence: 96%

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy

Balikci,

Eryilmaz,

Guler

et al. 2024

Front. Behav. Neurosci.

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Impact of Lyophilized Milk Kefir-Based Self-Nanoemulsifying System on Cognitive Enhancement via the Microbiota–Gut–Brain Axis

Anwar,

Boseila,

Mabrouk

et al. 2024

Antioxidants

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Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut–brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut–brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels.

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Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

Leitch

2024

IJMS

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Understanding the molecular mechanisms underlying the generation of absence seizures is crucial for developing effective, patient-specific treatments for childhood absence epilepsy (CAE). Currently, one-third of patients remain refractive to the antiseizure medications (ASMs), previously called antiepileptic drugs (AEDs), available to treat CAE. Additionally, these ASMs often produce serious side effects and can even exacerbate symptoms in some patients. Determining the precise cellular and molecular mechanisms directly responsible for causing this type of epilepsy has proven challenging as they appear to be complex and multifactorial in patients with different genetic backgrounds. Aberrant neuronal activity in CAE may be caused by several mechanisms that are not fully understood. Thus, dissecting the causal factors that could be targeted in the development of precision medicines without side effects remains a high priority and the ultimate goal in this field of epilepsy research. The aim of this review is to highlight our current understanding of potential causative mechanisms for absence seizure generation, based on the latest research using cutting-edge technologies. This information will be important for identifying potential targets for future therapeutic intervention.

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Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats)

Cited by 3 publications

References 115 publications

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy

Impact of Lyophilized Milk Kefir-Based Self-Nanoemulsifying System on Cognitive Enhancement via the Microbiota–Gut–Brain Axis

Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

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