scholarly journals Altered Expression of Par3, aPKC-λ, and Lgl1 in Hippocampus in Kainic Acid-Induced Status Epilepticus Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Zhang ◽  
Fafa Tian ◽  
Zheren Tan ◽  
Juan Du ◽  
Xiaoyan Long

Introduction: Mossy fiber sprouting (MFS) is a frequent histopathological finding in temporal lobe epilepsy (TLE) and is involved in the pathology of TLE. However, molecular signals underlying MFS remain unclear. Partitioning defective 3(Par3), atypical protein kinase C-λ(aPKC-λ), and lethal giant larvae 1(Lgl1) were involved in the neuronal polarity and axon growth. The potential roles of those proteins in MFS and epileptogenesis of TLE were investigated.Material and Methods: The epileptic rat models were established by intracerebroventricular injection of kainic acid (KA). The degree of MFS was measured by using Timm staining, Neuronal loss and the expression aPKC-λ, Par3, and Lgl1 in hippocampus were measured by using immunohistochemistry and western blot analysis.Results: The neuronal loss in CA3 region was observed from 3 days to 8 weeks, while the neuronal loss in the hilar region was observed from 1 to 8 weeks in experimental group. The Timm score in the CA3 region in experimental group was significantly higher than that in the control group from 2 to 8 weeks. Compared with control group, the expressions of Par3 and Lgl1 were upregulated and the expression of aPKC-λ was downregulated in the experimental groups. Positive correlation between the Par3 expression and Timm scores, and the negative correlation between the aPKC-λ expression and Timm scores in CA3 region were discovered in experimental group.Conclusion: The findings of the present study indicated that aPKC-λ, Par3, and Lgl1 may be involved in MFS and in the epileptogenesis of temporal lobe epilepsy.

2020 ◽  
Vol 22 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Maria Elisa Serrano ◽  
Mohamed Ali Bahri ◽  
Guillaume Becker ◽  
Alain Seret ◽  
Charlotte Germonpré ◽  
...  

Abstract Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.


2021 ◽  
Vol 22 (8) ◽  
pp. 3860
Author(s):  
Elisa Ren ◽  
Giulia Curia

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.


2021 ◽  
Vol 29 (1) ◽  
pp. 45-53
Author(s):  
Julia I. Medvedeva ◽  
Roman A. Zorin ◽  
Vladimir A. Zhadnov ◽  
Michael M. Lapkin

Aim. This study aimed to investigate the mechanisms of autonomic regulation and autonomic support in focal frontal and temporal lobe epilepsy. Materials and Methods. Thirty-six individuals were examined (19 men and 17 women; mean age 33.71.4 years) in the control group (without history of epileptic seizures) and 68 patients (32 men and 36 women, 34.11.5 years) with focal epilepsy (36 patients with frontal lobe epilepsy, of which 32 had temporal lobe epilepsy). Physiological parameters of heart rate variability and of skin sympathetic evoked potentials were evaluated. Results. Predomination of sympathetic influences in both groups of patients was found. According to the analysis of skin sympathetic evoked potentials, a high activity of the suprasegmental autonomic centers was determined in patients with epilepsy. Based on the results of the correlation analysis, the initial state in patients with temporal lobe epilepsy was characterized by greater intrasystemic tension that reflects the high level of physiological costs. The logit regression analysis model makes it possible to distribute patients with focal epilepsy into groups with different disease courses on the basis of the parameters of the autonomic support of the activity. Conclusion. In patients with focal epilepsy, predomination of sympathetic influences was observed, as well as greater activity of the suprasegmental centers of the autonomic regulation. Intrasystemic ratios of autonomic regulation parameters demonstrate an increase in the intrasystemic tension and a limitation of functional reserves in patients with temporal lobe epilepsy. A complex of parameters of autonomic support allows, based on the logit regression analysis, to distribute patients into groups with different courses of focal epilepsy.


2017 ◽  
Vol 134 ◽  
pp. 273-282 ◽  
Author(s):  
Yajie Chi ◽  
Bolin Wu ◽  
Jianwei Guan ◽  
Kuntai Xiao ◽  
Ziming Lu ◽  
...  

1997 ◽  
Vol 78 (4) ◽  
pp. 1860-1868 ◽  
Author(s):  
Michele L. Simmons ◽  
Gregory W. Terman ◽  
Charles Chavkin

Simmons, Michele L., Gregory W. Terman, and Charles Chavkin. Spontaneous excitatory currents and κ-opioid receptor inhibition in dentate gyrus are increased in the rat pilocarpine model of temporal lobe epilepsy. J. Neurophysiol. 78: 1860–1868, 1997. Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of mossy fiber collaterals into the dentate gyrus inner molecular layer. We have used the rat pilocarpine model of temporal lobe epilepsy to study the functional consequences of mossy fiber sprouting on excitatory activity and κ-opioid receptor-mediated inhibition. Using the whole cell voltage-clamp technique, we found that abnormal excitatory activity was evident in granule cells of the dentate gyrus from pilocarpine-treated rats. The frequency of spontaneous excitatory postsynaptic currents (EPSCs) was increased greatly in cells from tissue in which significant mossy fiber sprouting had developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in association with mossy fiber sprouting. Giant EPSCs also could be evoked by low-intensity stimulation of the perforant path. Mossy fibers release not only excitatory amino acids, but also opioid peptides. κ-Opioid receptor-mediated inhibition in normal Sprague-Dawley rats was seen only in hippocampal sections from the ventral pole. In pilocarpine-treated rats, however, kappa receptor-mediated effects were seen in both ventral and more dorsal sections. Thus in this model of temporal lobe epilepsy, several types of abnormal excitatory activity were observed, thereby supporting the idea that mossy fiber sprouting leads to recurrent excitatory connections. At the same time, inhibition of excitatory activity by κ-opioid receptors was increased, perhaps representing an endogenous anticonvulsant mechanism.


2012 ◽  
Vol 10 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Jackeline Moraes Malheiros ◽  
Beatriz Monteiro Longo ◽  
Alberto Tannús ◽  
Luciene Covolan

Magnetic resonance images are useful in the study of experimental models of temporal lobe epilepsy. The manganese-enhanced MRI (MEMRI) technique is of interest since it combines the effects caused by manganese on the increased contrast in activated cell populations, when competing with calcium in synaptic transmission. Thus, the purpose of this study was to investigate the temporal evolution of the contrast related to manganese in the acute phase of temporal lobe epilepsy induced by systemic pilocarpine and compare it to the expression of the c-Fos protein. During this phase, the intensity of the MEMRI signal was analyzed at three different time points (5, 15 or 30 minutes) after the onset of status epilepticus (SE). The group that was maintained in status epilepticus for 30 minutes showed a decrease in intensity of the signal in CA1 and the dentate gyrus (DG). There were no differences between the control group and the other groups treated with pilocarpine. The expression of the protein, c-Fos, in the same animals showed that even in the short-duration status epilepticus (5 minutes), there was already maximal cellular activation in subregions of the hippocampus (DG, CA1 and CA3). Under the experimental conditions tested, our data suggest that the MEMRI signal was not sensitive for the identification of detectable variations of cell activation in the acute phase of the pilocarpine model. Our findings are not consistent with the idea that manganese contrast reflects primarily alterations in cellular activity during SE when other signal-modifying elements can act.


Sign in / Sign up

Export Citation Format

Share Document