A systematic approach for identifying shared mechanisms in epilepsy and its comorbidities

Hoyt, Charles Tapley; Domingo‐Fernándéz, Daniel; Balzer, Nora Reka; Güldenpfennig, Anka; Hofmann‐Apitius, Martin

doi:10.1093/database/bay050

Cited by 8 publications

(3 citation statements)

References 52 publications

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“…We developed a workflow using git (https://git-scm.com), GitHub (https://github.com), PyBEL (44) and a novel PyBEL extension PyBEL-Git (39) in order to identify and address syntactical issues in the BEL documents generated during the AETIONOMY project [https://www.aetionomy.eu; (40–44) and exposed through the NeuroMMSig mechanism enrichment server (37).…”

Section: Methodsmentioning

confidence: 99%

Re-curation and rational enrichment of knowledge graphs in Biological Expression Language

et al. 2019

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The rapid accumulation of new biomedical literature not only causes curated knowledge graphs (KGs) to become outdated and incomplete, but also makes manual curation an impractical and unsustainable solution. Automated or semi-automated workflows are necessary to assist in prioritizing and curating the literature to update and enrich KGs. We have developed two workflows: one for re-curating a given KG to assure its syntactic and semantic quality and another for rationally enriching it by manually revising automatically extracted relations for nodes with low information density. We applied these workflows to the KGs encoded in Biological Expression Language from the NeuroMMSig database using content that was pre-extracted from MEDLINE abstracts and PubMed Central full-text articles using text mining output integrated by INDRA. We have made this workflow freely available at https://github.com/bel-enrichment/bel-enrichment .

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Section: Methodsmentioning

confidence: 99%

Re-curation and rational enrichment of knowledge graphs in Biological Expression Language

et al. 2019

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“…Carbamazepine (CBZ), currently not of first or second choice treatment for epilepsy in AD, has also beneficial effect in the biological progression of AD in animal models: 1) reduces glutamate-mediated excitotoxicity [118]; 2) increases noradrenergic tone [121] and 3) decreases the burden of amyloid plaques [9].…”

Section: Sodium Channel Blockersmentioning

confidence: 99%

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Altuna¹,

Olmedo²,

Carmona‐Iragui³

et al. 2022

Preprint

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Epilepsy and Alzheimer's disease (AD) incidence increase with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age and abnormal AD biomarkers in PET and or CSF are frequently found in late onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate progression of cognitive decline and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASM). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.

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“…In recent years, increasing evidence has indicated that epilepsy and behavioral and mood disorders share common underlying pathophysiological mechanisms (Chang et al, 2011 ; Helmstaedter and Witt, 2017 ; Hingray et al, 2019 ). However, these mechanisms underlying behavioral and mood disorder comorbidities in epilepsy remain elusive (Zarcone and Corbetta, 2017 ; Hoyt et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Brain Structural Changes in Kindled Rats Induced by Coriaria Lactone/Pentylenetetrazol

Qiu

Wang

et al. 2021

Front. Behav. Neurosci.

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Epilepsy is a common chronic neurological disease that is characterized by spontaneous seizures. It is commonly comorbid with behavioral and mood disorders. No studies have yet examined the behavioral or structural brain changes associated with coriaria lactone (CL)-induced and pentylenetetrazol (PTZ)-induced kindlings. This study examined whether the increased seizure susceptibility induced by CL/PTZ is accompanied by behavioral impairments and aimed to identify associated structural brain changes. Kindling models were induced using CL and PTZ, with 10 rats in each group. After successful kindling, rats were subjected to brain structural imaging using T2-weighted imaging and underwent behavioral tests, namely, the open field test, water maze tasks, and contextual fear conditioning. Voxel-based morphometry was then used to identify possible brain structural changes associated with kindling and/or behaviors. Support-vector machine learning was also applied for the integrative analysis of behavioral changes and structural brain imaging. In the open field test, both the CL (P = 0.04) and PTZ groups (P = 0.002) spent more time in the central area than the control group. Only the PTZ group (50.29 ± 29.56 s) showed a freezing time that was significantly less than that of the control group (94.8 ± 41.04 s; P = 0.024, Tukey's HSD-corrected) in contextual fear conditioning, which is suggestive of impaired fear-associated learning ability. Furthermore, brain imaging analysis revealed that the gray matter volume (GMV) of the hippocampus changed in both the CL and PTZ groups when compared to control. The support-vector machine learning model indicated that the retrosplenial dysgranular and primary somatosensory cortices were associated with both of the mentioned kindling models. Furthermore, the support-vector regression model results indicated that kindling-associated GMV changes can be used to predict general exploratory activity in the open field test. In conclusion, this is the first study to report greater general exploratory activity in a CL-induced kindling model. Moreover, the general exploratory activity in the open field test can be predicted by the GMV of brain regions associated with kindling.

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A systematic approach for identifying shared mechanisms in epilepsy and its comorbidities

Cited by 8 publications

References 52 publications

Re-curation and rational enrichment of knowledge graphs in Biological Expression Language

Re-curation and rational enrichment of knowledge graphs in Biological Expression Language

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Behavioral and Brain Structural Changes in Kindled Rats Induced by Coriaria Lactone/Pentylenetetrazol

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