Cnestis ferruginea Vahl ex DC (Connaraceae) downregulates expression of immediate early genes in kainic acid-induced temporal lobe epilepsy in mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emmanuel S. Ojo ◽  
Ismail O. Ishola ◽  
Olasunmbo Afolayan ◽  
Ayorinde B. James ◽  
Benneth Ben-Azu ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Preventive Treatment ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Early Genes ◽  
Fos Protein ◽  
Oxide Synthase

Abstract Objectives This study investigates the influence of Cnestis ferruginea (CF) on kainic acid (KA)-induced immediate early genes (IEGs) associated with hippocampal sclerosis in temporal lobe epilepsy (TLE) in mice. Methods Animals were randomly divided into preventive treatment; vehicle (10 mL/kg, p.o.) or CF (400 mg/kg, p.o.) for three consecutive days before KA (5 mg/kg, i.p.) on days 4 and 5. In the reversal model, KA (5 mg/kg, i.p.) was administered on days 1 and 2 before CF (400 mg/kg) administration on days 3–5. Animals were euthanized on day 5, 6 h after KA exposure in preventive model and 1 h after CF administration in reversal model to estimate markers of IEGs. Results KA upregulated the expression of c-Fos protein by 3.32-, 9.45-, 8.13-, and 8.66-fold in the hippocampal CA1, CA2, CA3, and DG regions, respectively. Also, KA elevated inducible nitric oxide synthase protein expression by 10.9-, 10.6-, 9.78-, and 9.51-fold. Besides, mRNA expression of brain-derived neurotrophic factors and heat shock protein was increased by 2.38- and 1.39-fold, respectively, after exposure to KA which were attenuated by CF. Conclusions CF attenuated KA-induced IEGs and could be used as an adjunct in TLE.

The significance of the expression of Fos protein in the brain for the classification of antipsychotics

1997 ◽  
Vol 9 (4) ◽  
pp. 143-150
Author(s):  
J. Korf ◽  
J.B. Sebens
Keyword(s):  
Nucleus Accumbens ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Early Genes ◽  
Onderzoek Naar ◽  
Fos Protein ◽  
The Brain

SamenvattingIn de afgelopen zes jaar is veel onderzoek verficht naar de effecten van antipsychotica op de regionale c-fos-expressie in de hersenen. Deze benadering biedt in een dierexperimentele proefopzet de mogelijkheid op cellulair niveau de effecten van psychofarmaca te bestuderen. Het fos-gen behoort tot de groep ‘immediate early genes’. Dit zijn genen die de transcriptie van andere, vaak onbekende genen reguleren. Een aantal aspecten van dit mechanisme wordt in deze bijdrage beschreven. Het onderzoek naar de effecten van antipsychotica op c-fos-expressie wordt samengevat en de betekenis voor de classificatie van antipsychotica benadrukt. Het blijkt dat deze farmaca effectief zijn in zowel de (meso)limbische gebieden (als nucleus accumbens, septum en amygdala) als ook in de basale ganglia. De relatieve effecten, wat betreft de c-fos-reactie, van de atypische antipsychotica (als clozapine en risperidon) zijn hoger in de limbische structuren, vergeleken met de effecten van de typische (als haloperidol). De potentie van de c-fos-methodiek voor verdere ontwikkelingen in dit gebied wordt aangegeven.

scholarly journals Lateralized phenotypic differences in females in the intrahippocampal kainic acid mouse model of temporal lobe epilepsy

2021 ◽  
Author(s):  
Cathryn A. Cutia ◽  
Leanna K. Leverton ◽  
Xiyu Ge ◽  
Rana Youssef ◽  
Lori T. Raetzman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Gain ◽  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Dorsal Hippocampus ◽  
Hippocampal Sclerosis ◽  
Endocrine Dysfunction ◽  
Seizure Focus ◽  
Reproductive Endocrine

AbstractClinical evidence indicates that patients with temporal lobe epilepsy (TLE) often show differential outcomes of comorbid conditions dependent on the lateralization of the seizure focus. However, whether a left or right seizure focus produces differential effects on comorbid outcomes has not been investigated in a rodent model of chronic recurrent seizures. Here, we used the intrahippocampal kainic acid (IHKA) mouse model of TLE to determine whether targeting of left or right dorsal hippocampus for injection produces different outcomes in hippocampal sclerosis, body weight gain, and multiple measures of reproductive endocrine dysfunction in female mice. At one, two, and four months after injection, in vivo measurements of estrous cycles and weight were followed by ex vivo examination of hippocampal sclerosis, circulating ovarian hormone and corticosterone levels, ovarian morphology, and pituitary gene expression. IHKA mice with right-targeted injection (IHKA-R) showed greater granule cell dispersion and pituitary Fshb expression compared to mice with left-targeted injection (IHKA-L). By contrast, pituitary expression of Lhb and Gnrhr were higher in IHKA-L mice compared to IHKA-R, but these values were not different from respective saline-injected controls. IHKA-L mice also showed an increased rate of weight gain compared to IHKA-R mice. Disruptions to estrous cyclicity, however, were similar in both IHKA-L and IHKA-R mice. These findings indicate that although major reproductive endocrine dysfunction phenotypes present similarly after targeting left or right dorsal hippocampus in the IHKA model of TLE, distinct latent mechanisms based on lateralization of seizure focus may contribute to produce similar emergent reproductive endocrine outcomes.Significance StatementPeople with epilepsy often develop comorbidities dependent on the side of the brain in which the seizures originate. However, the mechanisms linking laterality of seizure initiation side to different comorbidities are unknown. Here, we examined whether injection of kainic acid in the left or right hippocampus, a model of temporal lobe epilepsy, produces differential effects on hippocampal damage, weight gain, and measurements of female reproductive endocrine function in female mice. We found that hippocampal sclerosis, pituitary gene expression, and weight gain are influenced by the side of injection. These results are the first demonstration of changes in pituitary gene expression in a model of epilepsy and indicate that the hemisphere targeted in the intrahippocampal kainic acid model impacts phenotypic outcomes.

Angiotensin II Type 1 Receptor Blockade Inhibits the Expression of Immediate-Early Genes and Fibronectin in Rat Injured Artery

Circulation ◽  
1995 ◽  
Vol 92 (1) ◽  
pp. 88-95 ◽  
Author(s):  
Shokei Kim ◽  
Masaki Kawamura ◽  
Hideki Wanibuchi ◽  
Kensuke Ohta ◽  
Akinori Hamaguchi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Receptor Blockade ◽  
Early Genes ◽  
Injured Artery

scholarly journals Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

2021 ◽  
Vol 22 (8) ◽  
pp. 3860
Author(s):  
Elisa Ren ◽  
Giulia Curia
Keyword(s):  
Animal Models ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Current Knowledge ◽  
Focal Epilepsy ◽  
Ex Vivo ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Epileptogenic Zone ◽  
Epileptiform Discharges

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.

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