Article
Neurosciences
Benton S. Purnell, Mariana Alves, Detlev Boison
Summary: The epilepsies are a group of diseases characterized by spontaneous seizures and associated comorbidities, but current understanding of the underlying mechanisms is limited. Focusing on neurons has led to the development of anti-seizure medications, but not all aspects of seizure activity can be explained. The role of astrocytes, another type of brain cell, and their implications in epilepsy are explored in this review.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Helena Marcelino, Tiago M. A. Carvalho, Joana Tomas, Francisca Teles, Ana C. Honorio, Carolina B. Rosa, Ana R. Costa, Bruno M. Costa, Cecilia R. A. Santos, Ana M. Sebastiao, Jose F. Cascalheira
Summary: The study found that the inhibitory effect of adenosine on glioblastoma multiforme (GBM) cells is significantly weakened, possibly due to increased adenosine elimination by adenosine kinase. Additionally, adenosine also enhances the cytotoxic effect of homocysteine on human astrocytes.
Article
Biochemistry & Molecular Biology
Petr Fabera, Libor Uttl, Hana Kubova, Grygoriy Tsenov, Pavel Mares
Summary: LiCl/pilocarpine status epilepticus induces changes in ADK isoform expression and inhibiting ADK with 5-ITU affects hippocampal excitability. The study shows that SE leads to decreased excitability in immature rats 3 days after induction, followed by increased excitability after 20 days. 5-ITU demonstrates inhibitory effects on hippocampal excitability in SE rats. ADK isoforms also show altered expression levels in SE rats, indicating their involvement in hippocampal excitability and brain development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Daniela Madeira, Catia R. Lopes, Ana P. Simoes, Paula M. Canas, Rodrigo A. Cunha, Paula Agostinho
Summary: The study found that silencing the A(2A)R gene in astrocytes leads to deficits in hippocampal synaptic plasticity and memory. Astrocytic A(2A)R control astrocytic morphology and influence hippocampal synaptic plasticity and memory in adult mice.
Article
Neurosciences
Pandeng Xie, Siqi Liu, Qi Huang, Zhonghua Xiong, Jiahui Deng, Chongyang Tang, Ke Xu, Bo Zhang, Baijian He, Xiongfei Wang, Zhao Liu, Jing Wang, Jian Zhou, Yugang Guan, Guoming Luan, Tianfu Li, Feng Zhai
Summary: Deep brain stimulation (DBS) can reduce spontaneous recurrent seizures (SRS) in epileptic rats by inhibiting ADK and activating A(1) receptors (A(1)Rs).
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Neurosciences
Paul S. Buckmaster, Bianca Reyes, Tahsin Kahn, Megan Wyeth
Summary: This study evaluated seizure initiation zones in rats with temporal lobe epilepsy and found that the ventral hippocampal formation is the primary bilateral epileptogenic zone, while the dorsal hippocampus is a secondary epileptogenic zone. These findings are consistent with human patients and validate the use of LFP (local field potential) method for identifying seizure onset zones.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Fumika Takeuchi, Natsumi Nishikata, Mai Nishimura, Kenji Nagao, Masahito Kawamura
Summary: In this study, a modified ketogenic diet enriched with leucine was developed to enhance the antiseizure effects, indicating a potential new therapeutic option for patients with epilepsy.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Mengyi Guo, Tianfu Li
Summary: Epilepsy is a complex neurological syndrome that affects millions of people worldwide. Adenosine, as an important factor in the development and progression of epilepsy, can have dual functions in inhibiting seizures and preventing overall progress. Associated comorbidities with epilepsy also play a significant role, and adenosine augmentation therapies have the potential to improve the prognosis of epilepsy patients.
CURRENT DRUG TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Lamis Chamas, Isabelle Seugnet, Roseline Poirier, Marie-Stephanie Clerget-Froidevaux, Valerie Enderlin
Summary: This study investigated the protective mechanisms linking hypothyroidism and neuroinflammation. Hypothyroid WSB/EiJ mice showed no neuroinflammatory response and maintained hippocampal thyroid signaling despite low circulating thyroid hormone levels, while C57BL/6J mice exhibited disturbed thyroid signaling, accompanied by neuroinflammation and memory impairment. The results highlight the importance of the hippocampal thyroid regulatory system in glial reactivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Benton Purnell, Madhuvika Murugan, Raja Jani, Detlev Boison
Summary: Adenosine plays both beneficial and detrimental roles in epilepsy. Its benefits include seizure termination, vasodilatory effects, neuroprotection, and antiepileptogenic effects. Detriments include respiratory suppression, contribution to EEG suppression, prolonged increase in extracellular adenosine, excitatory effects via A(2A) receptor activation, and potential contributions to sleep alterations and SUDEP.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Meghan Gage, Megan Gard, Thimmasettappa Thippeswamy
Summary: This study reports the development of glial scars in the piriform cortex in rodents with systemic chemoconvulsant-induced status epilepticus. Glial scars were characterized by reactive microglia and astrocytes, and showed differences in density between male and female animals. Further investigation is needed to understand the mechanisms of scar development and potential mitigation strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Mengyi Guo, Jing Zhang, Jing Wang, Xiongfei Wang, Qing Gao, Chongyang Tang, Jiahui Deng, Zhonghua Xiong, Xiangru Kong, Yuguang Guan, Jian Zhou, Detlev Boison, Guoming Luan, Tianfu Li
Summary: In this study, the adenosine signaling in FCD type I and type II patients was analyzed, revealing upregulation of adenosine-metabolizing enzymes ADK and ADA, as well as adenosine-producing enzyme CD73 in BCs. Moreover, an increase in A(2A)R density, a decrease in GLT-1 levels, and an increase in mTOR levels were observed in FCD specimens. These findings suggest that dysregulation of the adenosine system is a common pathological feature of both FCD type I and type II, and may serve as a therapeutic target for epilepsy associated with FCD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Jiajun Zheng, Tingjie Li, Shuang Qi, Bing Qin, Jiandong Yu, Gong Chen
Summary: A novel gene therapy-mediated cell therapy was developed to regenerate GABAergic neurons in the hippocampus, reducing seizure activity in a rat TLE model. The conversion of astrocytes into GABAergic interneurons through NeuroD1 overexpression increased interneuron number and decreased spontaneous recurrent seizure activity. This approach not only rescued neuronal loss but also ameliorated cognitive and mood dysfunctions in the TLE rat model.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Psychiatry
Xuan Ju, Shengdong Wang, Pan Yan, Chunyan Zhu, Xiwen Hu, Jiezheng Dong, Zhonglin Tan
Summary: The combined therapy of REMSD and fluoxetine protects rats against depression-induced damage and apoptosis in the hippocampus via modulating the A1 adenosine receptor level, suggesting a potential treatment strategy for depression.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Julia L. Ergina, Dmitry Amakhin, Tatyana Y. Postnikova, Elena B. Soboleva, Aleksey Zaitsev
Summary: The increase in excitability of hippocampal neural networks after epileptiform activity is primarily achieved through postsynaptic mechanisms, while the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected.
Article
Endocrinology & Metabolism
Anela Blazevic, Anand M. Iyer, Marie-Louise F. Van Velthuysen, Johannes Hofland, Lindsey Oudijk, Wouter W. de Herder, Leo J. Hofland, Richard A. Feelders
Summary: Small-intestinal neuroendocrine tumors (SI-NETs) have a higher prevalence and worse prognosis in male patients. This study found that mesenteric metastasis and fibrosis were more common in men than women. The risk of mesenteric metastasis in women increased around menopause. The expression of estrogen receptor alpha and androgen receptor was observed in primary tumors and mesenteric metastases.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Endocrinology & Metabolism
Eline van der Valk, Ozair Abawi, Mostafa Mohseni, Amir Abdelmoumen, Vincent Wester, Bibian van der Voorn, Anand Iyer, Erica van den Akker, Sanne Hoeks, Sjoerd van den Berg, Yolanda de Rijke, Tobias Stalder, Elisabeth van Rossum
Summary: The study found a positive association between glucocorticoids measured in hair and anthropometric measurements, with the relation between hair cortisone and waist circumference being the most prominent. These findings suggest an altered setpoint of the hypothalamic-pituitary-adrenal axis with increasing central adiposity.
Review
Endocrinology & Metabolism
Robin Lengton, Anand M. Iyer, Eline S. van der Valk, Ellen K. Hoogeveen, Onno C. Meijer, Bibian van der Voorn, Elisabeth F. C. van Rossum
Summary: Increasing glucocorticoid exposure is linked to weight gain, with individuals with obesity often showing high cortisol values. Individual differences in glucocorticoid sensitivity, influenced by genetic and acquired factors, play a crucial role in response to glucocorticoids and personalized treatment options targeting the glucocorticoid receptor.
Article
Clinical Neurology
Cato M. Drion, Lieneke Kooijman, Derek Chan, Janna Berkhout, Erwin A. van Vliet, Wytse J. Wadman, Jan A. Gorter
Summary: The study found that curcumin can delay the development of epilepsy, but cannot prevent full kindling. The effects of curcumin on neuropathology were not significant, highlighting the need for further research into its potential as an anti-epileptic agent.
Article
Endocrinology & Metabolism
Anela Blazevic, Anand M. Iyer, Marie-Louise F. van Velthuysen, Johannes Hofland, Peter M. van Koestveld, Gaston J. H. Franssen, Richard A. Feelders, Marina Zajec, Theo M. Luider, Wouter W. de Herder, Leo J. Hofland
Summary: This study found a decreased expression of tryptophan and serotonin-metabolizing enzymes in the stroma of patients with MF. This may explain the increased profibrotic potential of serotonin and the variability in the development of fibrotic complications associated with SI-NETs.
ENDOCRINE CONNECTIONS
(2022)
Article
Cell Biology
Frances S. Cho, Ilia D. Vainchtein, Yuliya Voskobiynyk, Allison R. Morningstar, Francisco Aparicio, Bryan Higashikubo, Agnieszka Ciesielska, Diede W. M. Broekaart, Jasper J. Anink, Erwin A. van Vliet, Xinzhu Yu, Baljit S. Khakh, Eleonora Aronica, Anna Molofsky, Jeanne T. Paz
Summary: Inflammatory processes induced by brain injury are important for recovery, but uncontrolled inflammation can be harmful. Chronic activation of glial cells in the thalamus has been suggested as an indicator of increased seizure risk and cognitive deficits after cortical injury. This study found that thalamic inflammation was sufficient to cause cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms. Down-regulation of GAT-3 in thalamic astrocytes mediated this neurological dysfunction.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Mirte Scheper, Alessia Romagnolo, Zein Mersini Besharat, Anand M. Iyer, Romina Moavero, Christoph Hertzberg, Bernhard Weschke, Kate Riney, Martha Feucht, Theresa Scholl, Borivoj Petrak, Alice Maulisova, Rima Nabbout, Anna C. Jansen, Floor E. Jansen, Lieven Lagae, Malgorzata Urbanska, Elisabetta Ferretti, Aleksandra Tempes, Magdalena Blazejczyk, Jacek Jaworski, David J. Kwiatkowski, Sergiusz Jozwiak, Katarzyna Kotulska, Krzysztof Sadowski, Julita Borkowska, Paolo Curatolo, James D. Mills, Eleonora Aronica
Summary: This study used RNA sequencing analysis to define the expression patterns of miRNAs and isomiRs in the serum of patients with TSC, and identified potential circulating molecular biomarkers using ROC curve analysis to discriminate the development of neuropsychiatric comorbidity in TSC patients.
Article
Clinical Neurology
Dominique Frances Leitner, Sasha Devore, Juliana Laze, Daniel Friedman, James D. Mills, Yan Liu, Michael Janitz, Jasper J. Anink, Johannes C. Baayen, Sander Idema, Erwin Alexander van Vliet, Beate Diehl, Catherine Scott, Roland Thijs, Maromi Nei, Manor Askenazi, Shobi Sivathamboo, Terence O'Brien, Thomas Wisniewski, Maria Thom, Eleonora Aronica, Maura Boldrini, Orrin Devinsky
Summary: This study aimed to explore the molecular mechanisms of prolonged postictal generalized electroencephalographic suppression (PGES) in patients with epilepsy. It was found that higher hippocampal 5HT2A receptor protein and potassium channel transcripts may be associated with PGES. Further studies with larger cohorts are needed to elucidate the underlying mechanisms of PGES and SUDEP risk.
Review
Biochemistry & Molecular Biology
Jody M. de Jong, Diede W. M. Broekaart, Anika Bongaarts, Angelika Muhlebner, James D. Mills, Erwin A. van Vliet, Eleonora Aronica
Summary: Seizures are a common symptom of brain tumors, especially in paediatric-type tumors. The extracellular matrix plays a role in epileptogenesis and tumorigenesis. Understanding the epileptogenic properties of brain tumors is crucial for improving health outcomes and developing novel therapies.
Article
Biochemistry & Molecular Biology
Diede W. M. Broekaart, Till S. Zimmer, Sophie T. Cohen, Rianne Tessers, Jasper J. Anink, Helga E. de Vries, Jan A. Gorter, Roger Prades, Eleonora Aronica, Erwin A. van Vliet
Summary: The gelatinase inhibitor ACT-03 has shown disease-modifying effects in epilepsy models by reducing neuroinflammation and preserving blood-brain barrier integrity. Further evaluation of its effects in clinical trials is warranted.
Article
Clinical Neurology
Laura Bindila, Tore Eid, James D. Mills, Michael S. Hildebrand, Gary P. Brennan, Susan A. Masino, Vicky Whittemore, Piero Perucca, Christopher A. Reid, Manisha Patel, Kevin K. Wang, Erwin A. van Vliet
Summary: The International League Against Epilepsy/American Epilepsy Society established the TASK3 working groups to create common data elements for preclinical epilepsy research. This paper discusses the important elements for proteomics, lipidomics, and metabolomics methodologies and provides a rationale for documenting parameters.
Article
Biochemistry & Molecular Biology
Mette Heiskanen, Shalini Das Gupta, James D. Mills, Erwin A. van Vliet, Eppu Manninen, Robert Ciszek, Pedro Andrade, Noora Puhakka, Eleonora Aronica, Asla Pitkanen
Summary: Traumatic brain injury (TBI) is responsible for a significant percentage of structural and all epilepsies, but there is currently a lack of prognostic biomarkers for post-traumatic epilepsy (PTE). This study investigated the potential of plasma microRNAs (miRNAs) as biomarkers for brain damage severity and the development of PTE. The results showed that acutely altered plasma miRNA levels could reflect the extent of cortical injury, but they were not able to predict PTE development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Tessa N. A. Slagboom, Dirk Jan Stenvers, Elsmarieke van de Giessen, Stefan D. D. Roosendaal, Maartje M. L. de Win, Joseph C. J. Bot, Eleonora Aronica, Rene Post, Jantien Hoogmoed, Madeleine L. L. Drent, Alberto M. M. Pereira
Summary: The study provides a structured analysis of the diagnostic accuracy and clinical use of molecular imaging in patients with ACTH-dependent Cushing's syndrome, as well as the role of multidisciplinary counseling in decision making. It proposes a complementary diagnostic algorithm for both de novo and recurrent or persistent Cushing's disease. The use of molecular imaging modalities is of added and complementary value in the detection of pituitary microadenoma in ACTH-dependent Cushing's syndrome.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Valentina La Cognata, Agata Grazia D'Amico, Grazia Maugeri, Giovanna Morello, Maria Guarnaccia, Benedetta Magri, Eleonora Aronica, Velia D'Agata, Sebastiano Cavallaro
Summary: Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron (MN) depletion. CXCR2 has been implicated in ALS pathology and its expression is increased in cortical neurons of sporadic ALS patients. Inhibition of CXCR2 prevents MN degeneration in vitro and improves neuromuscular function in SOD1-G93A mice.
Article
Education & Educational Research
Damien S. Fleur, Max Marshall, Miguel Pieters, Natasa Brouwer, Gerrit Oomens, Angelos Konstantinidis, Koos Winnips, Sylvia Moes, Wouter van den Bos, Bert Bredeweg, Erwin A. van Vliet
Summary: Personalized peer-comparison feedback can be used to improve self-regulated learning and academic achievement. Providing meaningful feedback and peer comparison through a learning analytics dashboard offers a solution.
JOURNAL OF LEARNING ANALYTICS
(2023)