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Amygdala kindling

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https://www.readbyqxmd.com/read/29114861/kappa-opioid-receptors-regulate-hippocampal-synaptic-homeostasis-and-epileptogenesis
#1
Bridget N Queenan, Raymond L Dunn, Victor R Santos, Yang Feng, Megan N Huizenga, Robert J Hammack, Stefano Vicini, Patrick A Forcelli, Daniel T S Pak
OBJECTIVE: Homeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo. METHODS: We previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functional changes...
November 8, 2017: Epilepsia
https://www.readbyqxmd.com/read/29107199/kindling-epileptogenesis-and-panic-like-behavior-their-bidirectional-connection-and-contribution-to-epilepsy-associated-depression
#2
Jesús-Servando Medel-Matus, Don Shin, Raman Sankar, Andrey Mazarati
Anxiety is one of the most common comorbidities of epilepsy, which has major detrimental effects on the quality of life. Generalized anxiety disorder (GAD) associated with epilepsy has been receiving most attention. However, several other forms of anxiety reportedly present in patients with epilepsy, including panic disorder (PD). In this study, using an animal model of limbic epilepsy, we examined the interplay between epilepsy and panic-like behavior (PLB). Further, considering the high degree of comorbidity between depression on the one hand, and both epilepsy and PD on the other hand, we studied whether and how the presence of PLB in animals with epilepsy would affect their performance in depression-relevant tests...
October 26, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29090671/targeted-blockade-of-tarp-g8-associated-ampa-receptors-anticonvulsant-activity-with-the-selective-antagonist-ly3130481-cerc-611
#3
Jeffrey M Witkin, Douglas A Schober, Scott D Gleason, John T Catlow, Warren J Porter, Jon Reel, X Jin, J Hobbs, Donald Gehlert, Douglas L Gernert, Kevin M Gardinier, Akihiko S Kato, X Ping, J L Smith
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) g-8 that is under development for epilepsy. The present study provided a broad inquiry into its anticonvulsant properties. LY3130481 was anticonvulsant in multiple acute seizure provocation models in mice and rats. In addition, LY3130481 was effective against absence seizures in the GAERS genetic model and in the Frings mouse model...
November 1, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28948088/linking-kindling-to-increased-glutamate-release-in-the-dentate-gyrus-of-the-hippocampus-through-the-stxbp5-tomosyn-1-gene
#4
Seth R Batten, Elena A Matveeva, Sidney W Whiteheart, Thomas C Vanaman, Greg A Gerhardt, John T Slevin
INTRODUCTION: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling. METHODS: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1(-/-) (Tom(-/-)) animals...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28751143/n-alkyl-1-1-biphenyl-2-sulfonamide-derivatives-as-novel-broad-spectrum-anti-epileptic-drugs-with-efficacy-equivalent-to-that-of-sodium-valproate
#5
Tomoyuki Tanaka, Nana Yajima, Tomoko Kiyoshi, Yoshiki Miura, Seiji Iwama
In order to develop phenyl sulfonamides as a novel class of anti-epileptic drugs (AED) for both general and partial seizure, we initiated in vivo screening of our chemical library in the mice MES and sc-PTZ models and found compounds 1 and 2 as lead compounds. Optimization of 1 and 2 led to the discovery of compound 21, which showed potent anticonvulsant effect in MES, scPTZ and rat amygdala kindling models. These findings indicate that compound 21 could be a useful new broad spectrum AED like sodium valproate and provide an opportunity to struggle current therapy-resistant epilepsy...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28746840/quantitative-assessments-of-extracellular-eeg-to-classify-specific-features-of-main-phases-of-seizure-acquisition-based-on-kindling-model-in-rat
#6
Mostafa Jalilifar, Ali Yadollahpour, Ahmad Ali Moazedi, Zohreh Ghotbeddin
OBJECTIVE: Quantitative assessments of extracellular EEG to identify specific features of three main phases of seizure acquisition based on kindling model in Rat. METHODS: Male rats were divided into 2 groups including kindled (n=10) and sham (n=7) and respectively underwent an amygdala rapid kindling and placebo kindling. EEG signals in stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 generalized seizure stages (GSSs) were divided into 5 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-28Hz), and gamma (28-40Hz)...
July 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28710841/accelerated-kindling-epileptogenesis-in-tg4510-tau-transgenic-mice-but-not-in-tau-knockout-mice
#7
Shijie Liu, Yu Shen, Sandy R Shultz, Anne Nguyen, Christopher Hovens, Paul A Adlard, Ashley I Bush, Jianxiong Chan, Patrick Kwan, Terence J O'Brien, Nigel C Jones
The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild-type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks...
September 2017: Epilepsia
https://www.readbyqxmd.com/read/28674781/spike-densities-of-the-amygdala-and-neocortex-reflect-progression-of-kindled-motor-seizures
#8
Yu-Lin Wang, Sheng-Fu Liang, Alvin W Y Su, Fu-Zen Shaw
Amygdala kindling is a common temporal lobe-like seizure model. In the present study, temporal and spectral analyses of the ictal period were investigated throughout amygdala kindling in response to different behavioral seizures. Right-side amygdala was kindled to induce epileptiform afterdischarges (ADs). ADs of both the frontal cortex and amygdala were analyzed. Powers of the low (0-9 Hz)- and high (12-30 Hz)-frequency bands in response to different behavioral seizures were calculated. Densities of upward and downward peaks of spikes, which reflected information of spike count and spike pattern, throughout kindle-induced ADs were calculated...
July 4, 2017: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28570965/neurochemical-evidence-based-suggested-therapy-for-safe-management-of-epileptogenesis
#9
Navjot Kaur, Tanveer Singh, Sandeep Kumar, Rajesh Kumar Goel
Most of the clinically available antiepileptic drugs have only antiseizure effects and are reported unable to prevent epileptogenesis. In the past decade, several drugs underwent clinical trials for management of epileptogenesis, but none of the drugs tested was found effective. One of the major lacunas is availability of appropriate preclinical approaches to delineate mechanisms of epileptogenesis. Thus, the present study attempts to suggest a neurochemistry based approach for safe management of epileptogenesis...
May 29, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28502217/hippocampal-low-frequency-stimulation-inhibits-afterdischarge-and-increases-gaba-a-receptor-expression-in-amygdala-kindled-pharmacoresistant-epileptic-rats
#10
Guofeng Wu, Likun Wang, Zhen Hong, Siying Ren, Feng Zhou
OBJECTIVE: The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. METHODS: A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats)...
May 14, 2017: Neurological Research
https://www.readbyqxmd.com/read/28485718/transcriptional-profile-of-hippocampal-dentate-granule-cells-in-four-rat-epilepsy-models
#11
Raymond Dingledine, Douglas A Coulter, Brita Fritsch, Jan A Gorter, Nadia Lelutiu, James McNamara, J Victor Nadler, Asla Pitkänen, Michael A Rogawski, Pate Skene, Robert S Sloviter, Yu Wang, Wytse J Wadman, Claude Wasterlain, Avtar Roopra
Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling...
May 9, 2017: Scientific Data
https://www.readbyqxmd.com/read/28393712/therapeutic-role-of-synaptic-vesicle-glycoprotein-2a-sv2a-in-modulating-epileptogenesis
#12
Yukihiro Ohno, Kentaro Tokudome
Dysfunction of synaptic neurotransmitter release is closely involved in the pathogenesis of various central nervous system diseases. Synaptic vesicle glycoprotein 2A (SV2A) is a membrane protein specifically expressed in synaptic vesicles and it modulates action potential-dependent neurotransmitter release in the brain. Since 1) SV2A-knockout mice exhibit severe convulsive seizures, 2) SV2A expression in the brain is reportedly altered in various epileptic disorders both in animal models (e.g., kindling and genetic models) and humans (e...
April 4, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28336934/low-frequency-stimulation-of-the-primary-focus-retards-positive-transfer-of-secondary-focus
#13
Yifang Kuang, Cenglin Xu, Yinxi Zhang, Yi Wang, Xiaohua Wu, Ying Wang, Yao Liu, Kai Zhong, Hui Cheng, Yi Guo, Shuang Wang, Meiping Ding, Zhong Chen
Positive transfer of secondary focus (PTS) refers to new epileptogenesis outside the primary focus and is minimally controlled by existing treatments. Low-frequency stimulation (LFS) has benefits on the onset of epilepsy and epileptogenesis. However, it's unclear whether LFS can retard the PTS in epilepsy. Here we found that PTS at both contralateral amygdala and ipsilateral hippocampus were promoted after the primary focus was fully kindled in rat kindling model. The promotion of PTS at the mirror focus started when the primary kindling acquisition reached focal seizures...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28214547/cerebral-small-vessel-disease-predisposes-to-temporal-lobe-epilepsy-in-spontaneously-hypertensive-rats
#14
Emilio Russo, Antonio Leo, Francesca Scicchitano, Annalidia Donato, Edoardo Ferlazzo, Sara Gasparini, Vittoria Cianci, Chiara Mignogna, Giuseppe Donato, Rita Citraro, Umberto Aguglia, Giovambattista De Sarro
The link between cerebral small vessel disease (CSVD) and epilepsy has been poorly investigated. Some reports suggest that CSVD may predispose to temporal lobe epilepsy (TLE). Aim of this study was to evaluate whether spontaneously hypertensive rats (SHRs), an established model of systemic hypertension and CSVD, have a propensity to develop TLE more than generalized seizures. To this aim, amygdala kindling, as a model of TLE, and pentylenetetrazole (PTZ)-induced kindling, as a model of generalized seizures, have been used to ascertain whether SHRs are more prone to TLE as compared to Wistar Kyoto control rats...
February 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28167431/adeno-associated-viral-vector-mediated-preprosomatostatin-expression-suppresses-induced-seizures-in-kindled-rats
#15
Gowri Natarajan, Jeffrey A Leibowitz, Junli Zhou, Yang Zhao, Jessica A McElroy, Michael A King, Brandi K Ormerod, Paul R Carney
Somatostatin is expressed widely in the hippocampus and notably in hilar GABAergic neurons that are vulnerable to seizure neuropathology in chronic temporal lobe epilepsy. We previously demonstrated that sustained bilateral preprosomatostatin (preproSST) expression in the hippocampus prevents the development of generalized seizures in the amygdala kindling model of temporal lobe epilepsy. Here we tested whether sustained preproSST expression is anticonvulsant in rats already kindled to high-grade seizures. Rats were kindled until they exhibited 3 consecutive Racine Grade 5 seizures before adeno-associated virus serotype 5 (AAV5) vector driving either eGFP (AAV5-CBa-eGFP) or preproSST and eGFP (AAV5-CBa-preproSST-eGFP) expression was injected bilaterally into the hippocampal dentate gyrus and CA1 region...
February 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28124605/increase-signaling-of-wnt-%C3%AE-catenin-pathway-and-presence-of-apoptosis-in-cerebellum-of-kindled-rats
#16
Carmen Rubio-Osornio, Artemio Rosiles-Abonce, Cristina Trejo-Solís, Moisés Rubio-Osornio, Cesar Mendoza, Verónica Custodio, Juan Carlos Martínez-Lazcano, Edith González, Carlos Paz
Epilepsy is one of the most common neurological disorders in humans, and the role of the cerebellum in its physiopathology remains the subject of study. The Purkinje cells (PC), whose axons target the dentate and interpositus nuclei, form the main cerebellar output to forebrain structures involved in epilepsy. Cerebellar atrophy related to loss of PC has been reported in chronic epilepsy although its mechanism remains unclear. Taking in account that an overexpression of β-Catenin has been related with cell death, here we present the signaling of β-Catenin and the type of PC death in cerebellum of rats with chronic seizures induced by the amygdaloid kindling model...
January 17, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28097810/physicochemical-and-biological-evaluation-of-a-cinnamamide-derivative-r-s-2e-1-3-hydroxypiperidin-1-yl-3-phenylprop-2-en-1-one-km-608-for-nervous-system-disorders
#17
Agnieszka Gunia-Krzyżak, Ewa Żesławska, Florence M Bareyre, Wojciech Nitek, Anna M Waszkielewicz, Henryk Marona
A cinnamamide scaffold has been successfully incorporated in several compounds possessing desirable pharmacological activities in central and peripheral nervous system such as anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative/hypnotic properties. R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608), a cinnamamide derivative, was synthesized, its chemical structure was confirmed by means of spectroscopy and crystallography, and additionally, thermal analysis showed that it exists in one crystalline form...
August 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28012162/evidence-for-a-differential-interaction-of-brivaracetam-and-levetiracetam-with-the-synaptic-vesicle-2a-protein
#18
Martyn D Wood, Michel Gillard
OBJECTIVE: Brivaracetam (BRV) and levetiracetam (LEV) are effective antiepileptic drugs that bind selectively to the synaptic vesicle 2A (SV2A) protein. However, BRV differs from LEV in that it exhibits more potent and complete seizure suppression in animal models including in amygdala-kindled mice, where BRV afforded nearly complete seizure suppression. This raises the possibility that aside from potency differences, BRV and LEV may interact differently with the SV2A protein, which is not apparent in radioligand-binding competition studies...
February 2017: Epilepsia
https://www.readbyqxmd.com/read/27891086/circuits-regulating-pleasure-and-happiness-mechanisms-of-depression
#19
Anton J M Loonen, Svetlana A Ivanova
According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27875989/interleukin-1-receptor-il-1r-mediates-epilepsy-induced-sleep-disruption
#20
Tzu-Rung Huang, Shuo-Bin Jou, Yu-Ju Chou, Pei-Lu Yi, Chun-Jen Chen, Fang-Chia Chang
BACKGROUND: Sleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epileptogenesis; however, few studies emphasize the effect of IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1 receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy-induced sleep disturbances...
November 22, 2016: BMC Neuroscience
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