Article
Behavioral Sciences
Ekram Mohammadi, Farnaz Nikbakht, Somayeh Vazifekhah, Javad Fahanik Babae, Mohamad Taghi Jogataei
Summary: Memory impairment is a common issue in patients with temporal lobe epilepsy. N-acetyl cysteine (NAC) has neuroprotective effects and can delay seizure activity and improve memory deficits.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Chihiro Hisatsune, Tadayuki Shimada, Akitoshi Miyamoto, Amy Lee, Kanato Yamagata
Summary: Tuberous sclerosis complex (TSC) is a developmental disorder characterized by hamartomas in various organs and is often associated with epilepsy. Research has found that TSC2-deficient neurons exhibit heightened neuronal activity with synchronized Ca2+ spikes, with L-type calcium channels (LTCCs) playing a critical role in this abnormal activity. Targeting LTCCs could be a potential novel approach for treating epilepsy in TSC patients.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Dongsheng Gao, Linqing Ma, Yunliang Xie, Bo Xiao, Shouru Xue, Wenbiao Xiao, You Zhou, Xiuying Cai, Xiaoyan Yang
Summary: Temporal lobe epilepsy (TLE) is a complex neurological disease with links to the autophagy signaling pathway. This study found that electroacupuncture (EA) treatment can promote autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway. Increased mature neuron numbers were observed in TLE rats treated with EA.
NEUROCHEMICAL RESEARCH
(2022)
Review
Behavioral Sciences
Wei Zhao, Cong Xie, Xu Zhang, Ju Liu, Jinzhi Liu, Zhangyong Xia
Summary: Epilepsy is a common and serious brain syndrome that has adverse effects on a patient's wellbeing and quality of life. The dysregulation of the mTOR pathway is believed to play a significant role in the development and progression of epilepsy. This review discusses the role of the mTOR signaling pathway in epilepsy pathogenesis and the potential use of mTOR inhibitors for treatment.
BRAIN AND BEHAVIOR
(2023)
Article
Genetics & Heredity
Yishu Wang, Jing Peng, Shuwei Bai, Haojun Yu, Hong He, Chunxiang Fan, Yong Hao, Yangtai Guan
Summary: Temporal lobe epilepsy (TLE), the most common form of refractory epilepsy in adults, may require surgery to alleviate seizures. Research suggests that a mutation in the PIK3R2 gene may play a significant role in the development of TLE.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Leila Zummo, Alessandra Maria Vitale, Celeste Caruso Bavisotto, Marco De Curtis, Rita Garbelli, Anna Teresa Giallonardo, Carlo Di Bonaventura, Martina Fanella, Everly Conway de Macario, Francesco Cappello, Alberto J. L. Macario, Antonella Marino Gammazza
Summary: miRNAs and the chaperone system are promising targets for understanding the pathogenic mechanisms of epilepsy and developing theranostics applications. They could serve as useful biomarkers for diagnosis, patient monitoring, and as targets for novel therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Nadim Jaafar, Amar Bhatt, Alexandra Eid, Mohamad Z. Koubeissi
Summary: Some surgical failures after temporal lobe epilepsy surgery may be caused by the presence of extratemporal epileptogenic zones, particularly in the medial parietal lobe. Seizures originating from this area may not cause obvious symptoms before spreading to the temporal lobe.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Hua Tao, Zengqiang Chen, Jianhao Wu, Jun Chen, Yusen Chen, Jiawu Fu, Chaowen Sun, Haihong Zhou, Wangtao Zhong, Xu Zhou, Keshen Li
Summary: This study found significantly lower DNA methylation levels of genes encoding ion channels in TLE patients compared to healthy controls. Ten of these genes exhibited differential DNA methylation levels in the TLE group, serving as potential independent risk factors. Methylation alterations may influence the expression of ion channel proteins, playing a key role in the pathogenesis of TLE.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Willian Lazarini-Lopes, Gleice Kelli Silva-Cardoso, Christie Ramos Andrade Leite-Panissi, Norberto Garcia-Cairasco
Summary: This study investigated the impact of chronic epileptic seizures on anxiety-like behavior and TRPV1 channel expression in a genetic model of epilepsy. The results showed increased anxiety-like behavior in the model rats and alterations in TRPV1 expression in brain structures involved with epilepsy and anxiety comorbidity.
Article
Medicine, General & Internal
Kai-Feng Shen, Xiao-Lin Yang, Guo-Long Liu, Gang Zhu, Zhong-Ke Wang, Xian-Jun Shi, Ting-Ting Wang, Zhi-Feng Wu, Sheng-Qing Lv, Shi-Yong Liu, Hui Yang, Chun-Qing Zhang
Summary: The study revealed that ClC-mediated current was increased in the hippocampal neurons of chronic TLE mice. Application of chloride channel blockers NPPB and DIDS reduced the current and increased inhibitory synaptic transmission in TLE mice. These drugs also decreased seizure frequency and the average power of ictal high-frequency oscillations in TLE mice.
Article
Clinical Neurology
Krzysztof Sadowski, Kamil Sijko, Dorota Domanska-Pakiela, Julita Borkowska, Dariusz Chmielewski, Agata Ulatowska, Sergiusz Jozwiak, Katarzyna Kotulska
Summary: Rapamycin can be used to treat drug-resistant epilepsy in children with TSC, and can effectively reduce the frequency of seizures at a certain dosage. The combination with vigabatrin has better efficacy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Lin-ming Zhang, Ling Chen, Yi-fei Zhao, Wei-mei Duan, Lian-mei Zhong, Ming-wei Liu
Summary: Potassium channel genes linked to temporal lobe epilepsy (TLE) were identified using bioinformatic analysis. Protein-protein interaction and gene set enrichment analysis revealed their association with cation channel, respiratory chain, and oxidative phosphorylation. mRNA-transcription factor and ceRNA networks revealed their interactions with transcription factors and non-coding RNAs. Drug targeting analysis suggested the potential therapeutic relevance of these genes. Overall, this study provides important gene information for understanding and treating TLE.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Erica Leandro Marciano Vieira, Flavia Mendes Amaral Martins, Paula Maria Quaglio Bellozi, Ana Paula Goncalves, Jose Mauricio Siqueira, Alexandre Gianetti, Antonio Lucio Teixeira, Antonio Carlos Pinheiro de Oliveira
Summary: The study found that cytokine production by immune cells in patients with temporal lobe epilepsy differs from non-epileptic patients, which may be associated with altered activity and responsiveness of intracellular molecules such as PI3K, mTOR, and GSK-3, contributing to the inflammatory state and pathogenesis of epilepsy.
NEUROSCIENCE LETTERS
(2021)
Article
Clinical Neurology
Dahye Kim, June Sic Kim, Woorim Jeong, Min-Sup Shin, Chun Kee Chung
Summary: Selective resection in mesial temporal lobe epilepsy surgery has been shown to effectively preserve postoperative memory function, with specific areas of resection correlating with memory decline. This suggests the importance of selective resection to protect memory function in temporal lobe surgery.
JOURNAL OF NEUROSURGERY
(2021)
Article
Clinical Neurology
Valeri Borger, Motaz Hamed, Julia Taube, Gulsah Aydin, Inja Ilic, Matthias Schneider, Patrick Schuss, Erdem Guresir, Albert Becker, Christoph Helmstaedter, Christian E. Elger, Hartmut Vatter
Summary: Temporal lobe epilepsy (TLE) is a common form of epilepsy, and about 30% of patients have drug-resistant seizures. This study evaluated the seizure outcomes of patients with drug-refractory TLE who underwent resective temporal lobe surgery (rTLS), finding that the lack of MRI lesions and placement of depth electrodes before surgery were associated with unfavorable postsurgical seizure outcomes.
JOURNAL OF NEUROSURGERY
(2021)
Article
Biochemistry & Molecular Biology
E. R. Workman, F. Niere, K. F. Raab-Graham
MOLECULAR PSYCHIATRY
(2018)
Article
Biochemistry & Molecular Biology
Anushree N. Karkhanis, Amy C. Leach, Jordan T. Yorgason, Ayse Uneri, Samuel Barth, Farr Niere, Nancy J. Alexander, Jeffrey L. Weiner, Brian A. McCool, Kimberly F. Raab-Graham, Mark J. Ferris, Sara R. Jones
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Neurosciences
Gregory J. Ordemann, Christopher J. Apgar, Darrin H. Brager
JOURNAL OF NEUROPHYSIOLOGY
(2019)
Article
Neurosciences
Sarah A. Wolfe, Sean P. Farris, Joshua E. Mayfield, Chelcie F. Heaney, Emma K. Erickson, R. Adron Harris, R. Dayne Mayfield, Kimberly F. Raab-Graham
Article
Neurosciences
Sarah E. Ewin, James W. Morgan, Farr Niere, Nate P. McMullen, Samuel H. Barth, Antoine G. Almonte, Kimberly F. Raab-Graham, Jeffrey L. Weiner
Article
Neurosciences
Durgesh Tiwari, Darrin H. Brager, Jeffrey K. Rymer, Alexander T. Bunk, Angela R. White, Nada A. Elsayed, Joseph C. Krzeski, Andrew Snider, Lindsay M. Schroeder Carter, Steve C. Danzer, Christina Gross
NEUROBIOLOGY OF DISEASE
(2019)
Article
Neurosciences
Federico Brandalise, Brian E. Kalmbach, Preeti Mehta, Olivia Thornton, Daniel Johnston, Boris Zemelman, Darrin H. Brager
JOURNAL OF NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Chelcie F. Heaney, Sanjeev V. Namjoshi, Ayse Uneri, Eva C. Bach, Jeffrey L. Weiner, Kimberly F. Raab-Graham
Summary: Rapid antidepressants work by regulating FMRP expression in dendrites and modulating the mTORC1 pathway. The behavioral effects of Ro-25-6981 are dependent on FMRP expression and its differential mRNA binding controlled by mTORC1. In animal models with FXS, GABA(B)R activity can hinder the effects of Ro-25-6981, indicating a need for combined therapy targeting GABA(B)Rs and NMDARs in individuals with comorbid FXS and MDD.
MOLECULAR PSYCHIATRY
(2021)
Article
Substance Abuse
Aaron Deal, Nicholas Cooper, Haley Ann Kirse, Ayse Uneri, Kimberly Raab-Graham, Jeffrey L. Weiner, Leah C. Solberg Woods
Summary: This study investigated the impact of adolescent social isolation on anxiety and alcohol use disorder-like behaviors using rat models. The results showed that HS rats were protected against the negative effects of ASI, particularly in anxiety-like behavior and ethanol self-administration. The lack of changes in SK2 and GluA1 expression levels in the vHC may play a role in conferring this protection.
Article
Neurosciences
Gregory J. Ordemann, Christopher J. Apgar, Raymond A. Chitwood, Darrin H. Brager
Summary: Fragile X syndrome (FXS) is a major genetic cause of cognitive impairment and autism spectrum disorder. In FXS, impairment of TA-LTP, attributed to changes in A-type K+ channels, may contribute to spatial memory alterations.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Brianna E. George, Samuel H. Barth, Lindsey B. Kuiper, Katherine M. Holleran, Ryan T. Lacy, Kimberly F. Raab-Graham, Sara R. Jones
Summary: Evidence suggests that females are more vulnerable to the harmful effects of drugs like opioids, with increased heroin-related deaths seen in females. While males and females showed similar acquisition rates for heroin self-administration (SA), females exhibited increased responding and intake, seeking behavior, and escalation. The study found no differences in mu-opioid receptor (MOR) expression levels between males and females in the brain, but observed differential dopamine terminal adaptations in females that may contribute to their increased heroin-seeking behavior.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Brandy N. Routh, Darrin H. Brager, Daniel Johnston
Summary: Many types of neuronal cells have variable excitability in the subthreshold voltage range due to different contributions of voltage-gated ion channels. In layer 2/3 pyramidal neurons within the primary visual cortex, these voltage-dependent responses affect sensory processing but the specific ion channels involved are unknown. In this study, physiological recordings in mouse primary visual cortex identified several voltage-dependent channels that contribute to the dynamic gain of membrane responses in layer 2/3 pyramidal neurons. The data also revealed a correlation between the steepness of the membrane response and the number of branches on the proximal apical dendrite.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Neurosciences
Sarah E. Sizer, Michaela E. Price, Brian C. Parrish, Samuel H. Barth, Chelcie F. Heaney, Kimberly F. Raab-Graham, Brian A. McCool
Summary: This study found that both ethanol exposure and withdrawal enhance the excitability of NBM cholinergic neurons and promote glutamate release through activation of presynaptic nicotinic acetylcholine receptors. Additionally, ethanol withdrawal increases the modulatory effect of NBM terminal activity on BLA pyramidal neurons.
Article
Neurosciences
Federico Brandalise, Brian. E. E. Kalmbach, Erik. P. P. Cook, Darrin. H. H. Brager
Summary: Patients with Fragile X syndrome have impairments in the prefrontal cortex, affecting working memory and attention. Synaptic inputs to the dendrites of layer 5 pyramidal neurons in the prefrontal cortex have a weak influence on the somatic membrane potential, but are transformed into dendritic spikes to trigger action potential output. The dendritic spike generation is impaired in Fragile X mice, potentially altering the integration of sensory signals and motor actions in the prefrontal cortex circuits.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Physiology
Lauren T. Hewitt, Gregory J. Ordemann, Darrin H. Brager
Summary: In this study, the authors identified highly heterogeneous spike frequency adaptation in low threshold inhibitory interneurons in the mouse hippocampal CA1 stratum oriens region. Strong SFA cells were characterized by firing fewer action potentials and having lower input resistance compared to weak SFA cells, along with other physiological differences. They were labeled as a previously uncharacterized type of interneuron named Low Threshold High I-h (LTH) cells.
PHYSIOLOGICAL REPORTS
(2021)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)