Article
Clinical Neurology
Hyungwoo Lee, Kijeong Lee, Young Dae Kim, Hyo Suk Nam, Hye Sun Lee, Sunghee Cho, Ji Hoe Heo
Summary: This retrospective observational study of 350 patients with basal ganglia infarction found that degeneration of the substantia nigra (SN) was associated with functional dependence or death at 3 months post-stroke. The presence of SN degeneration was significantly correlated with worse functional outcomes, indicating its potential as a predictive factor for poor stroke prognosis and a target for therapeutic interventions.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Sebastian Hormigo, Ji Zhou, Manuel A. Castro-Alamancos
Summary: The results show that unilateral excitation and inhibition of SNr neurons can generate orienting movements in opposite directions, each with distinct behavioral significance.
Article
Multidisciplinary Sciences
Patricia Gonzalez-Rodriguez, Enrico Zampese, Kristen A. Stout, Jaime N. Guzman, Ema Ilijic, Ben Yang, Tatiana Tkatch, Mihaela A. Stavarache, David L. Wokosin, Lin Gao, Michael G. Kaplitt, Jose Lopez-Barneo, Paul T. Schumacker, D. James Surmeier
Summary: Loss of functional mitochondrial complex I in dopaminergic neurons can lead to a shift in metabolism in mice, causing Parkinson's disease-like symptoms. This study challenges the traditional paradigm of Parkinson's disease by showing that dysfunction of mitochondrial complex I alone is sufficient to cause progressive parkinsonism.
Article
Neurosciences
Suthinee Attachaipanich, Takaaki Ozawa, Tom Macpherson, Takatoshi Hikidap
Summary: The nucleus accumbens (NAc) is a crucial part of the limbic basal ganglia circuit and is associated with decision-making and reward processing. This study investigated the effects of optogenetic manipulation of the NAc D1-MSN-SNr pathway on reward learning and locomotor behavior in male mice. The results showed that stimulation of this pathway induced a preference for a laser-paired location, self-stimulation, and enhanced instrumental responding for a liquid reward. Furthermore, stimulation increased locomotor behavior when delivered bilaterally and induced contralateral turning behavior when delivered unilaterally. However, inhibition of this pathway had no effect on reward-related behaviors or locomotion.
Article
Neurosciences
Mario Antonazzo, Sonia Maria Gomez-Urquijo, Luisa Ugedo, Teresa Morera-Herreras
Summary: The basal ganglia (BG) play a role in movement control, cognitive, and motivational functions, with the CB1 cannabinoid receptor and dopamine playing key roles in BG circuits. Research shows that loss of dopamine alters information processing in the circuits, potentially leading to non-motor symptoms in Parkinson's disease patients.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Victoria Cheung, Philip Chung, Max Bjorni, Varvara A. Shvareva, Yesenia C. Lopez, Evan H. Feinberg
Summary: Behavioral roles and physiology of projection neurons connecting different brain areas are a major focus in modern neuroscience. A high throughput sequencing method called VECTORseq has been developed to identify multiple neuronal subtypes based on connectivity, providing a roadmap for future research in this area.
Article
Neurosciences
Wenyue Liu, Changpeng Wang, Tingting He, Minghong Su, Yuan Lu, Guanyu Zhang, Thomas F. Munte, Lirong Jin, Zheng Ye
Summary: In Parkinson's disease, damage to the substantia nigra may lead to deficits in sequential working memory, mediated by dysfunction in the basal ganglia. Patients showed poorer performance in a digitordering task and smaller SNs compared to healthy controls. The study suggests that SN integrity is crucial for sequencing performance in PD patients.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ilaria Palmieri, Tino Emanuele Poloni, Valentina Medici, Susanna Zucca, Annalisa Davin, Orietta Pansarasa, Mauro Ceroni, Livio Tronconi, Antonio Guaita, Stella Gagliardi, Cristina Cereda
Summary: The study compared two cases of different forms of dementia, highlighting similarities and differences in pathology, genetics, and transcriptomics, emphasizing the important role of transcriptome profiling in understanding the pathogenesis of AD and LBD.
Article
Multidisciplinary Sciences
Mariam Al Shamsi, M. Emdadul Haque, Allen Shahin, Sami Shaban, Abdul-Kader Souid
Summary: The study investigated the effects of two inhibitors of NADH:ubiquinone oxidoreductase on cellular respiration in striatal tissue using a phosphorescence oxygen analyzer. The results showed impaired respiration in the presence of the inhibitors, suggesting that striatal cellular respiration may be a sensitive biomarker for the adverse effects of toxins.
Article
Neurosciences
Juha Partanen, Kaia Achim
Summary: The Substantia Nigra pars reticulata (SNpr) plays a major role in the basal ganglia network, particularly in movement regulation, behavioral state adjustment, and response to reward. It also has the potential for signal integration and action selection. This article discusses the regionalization of SNpr, specifically the division of its neurons into anterior and posterior subtypes, and how their unique developmental and molecular characteristics may correlate with region-specific connections and functional specializations of SNpr. Understanding the differentiation of SNpr neurons can provide insights into fundamental brain functions and neurological disorders.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Kathryn L. Todd, Janusz Lipski, Peter S. Freestone
Summary: This study identified a distinct population of dopamine neurons that project to the tail region of the striatum, separate from the classic nigrostriatal pathway. The tail striatum was found to have lower basal and evoked dopamine levels, as well as diverse dopamine release kinetics compared to the dorsolateral striatum. Stimulation of the subthalamic nucleus (STN) exclusively evoked dopamine release in the tail striatum, likely mediated by the SNL. These findings suggest the existence of a novel dopamine pathway to the tail striatum, largely independent of the classic nigrostriatal pathway, and highlight the STN as an important modulator of dopamine release in this pathway.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Clinical Neurology
Koji Furukawa, Atsushi Shima, Daisuke Kambe, Akira Nishida, Ikko Wada, Haruhi Sakamaki, Kenji Yoshimura, Yuta Terada, Yusuke Sakato, Masahiro Mitsuhashi, Masanori Sawamura, Etsuro Nakanishi, Yosuke Taruno, Hodaka Yamakado, Yasutaka Fushimi, Tomohisa Okada, Yuji Nakamoto, Ryosuke Takahashi, Nobukatsu Sawamoto
Summary: This study investigates the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss in different stages of Parkinson's disease. The findings suggest that striatal dopaminergic terminal loss is a biomarker for early stage motor impairments, while nigral dopamine neuron loss is a biomarker for advanced stage motor impairments.
ANNALS OF NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Vladimir Hachinski, Leif Ostergaard
Summary: The article introduces a new evolutionary interpretation of the brain's circulation, emphasizing the importance of balancing low-pressure and high-pressure systems for optimal brain health.
Article
Multidisciplinary Sciences
Kazutaka Maeda, Ken-ichi Inoue, Masahiko Takada, Okihide Hikosaka
Summary: This study found that amygdala neurons are sensitive to environments and may regulate dopamine neurons through an inhibitory projection. Using optogenetics and multi-channel recording, the researchers demonstrated that rewarding environments have sustained effects on dopamine neuron activity and can elicit phasic responses to rewarding events. These findings suggest that the amygdala may provide an additional source of learning to basal ganglia circuits, specifically regarding environmental contingencies.
NATURE COMMUNICATIONS
(2023)
Article
Neuroimaging
Samantha Tan, Septian Hartono, Thomas Welton, Chu Ning Ann, Soo Lee Lim, Tong San Koh, Huihua Li, Fiona Setiawan, Samuel Ng, Nicole Chia, Saifeng Liu, E. Mark Haacke, Eng King Tan, Louis Chew Seng Tan, Ling Ling Chan
Summary: QSM and DKI are complementary tools that provide valuable insights into the complex pathological changes in early Parkinson's disease, particularly in relation to iron deposition and microstructural alterations. These technologies have the potential to be clinically useful for early diagnosis and assessment of PD.
NEUROIMAGE-CLINICAL
(2021)
Article
Clinical Neurology
Marie Johne, Kerstin Roemermann, Philip Hampel, Bjoern Gailus, Wiebke Theilmann, Tommi Ala-Kurikka, Kai Kaila, Wolfgang Loescher
Summary: The study evaluated the effect of bumetanide as an adjunct to phenobarbital on neonatal seizures, showing that bumetanide does not increase the efficacy of phenobarbital in a model of birth asphyxia.
Article
Behavioral Sciences
Philip Hampel, Kerstin Roemermann, Martina Gramer, Wolfgang Loescher
Summary: Bumetanide, azosemide, and torasemide all inhibit NKCC1 activity, but their distribution in the brain is limited, possibly due to efflux transport at the blood-brain barrier. Despite low levels of free fractions in plasma and brain, the free brain concentrations of bumetanide and torasemide fall within the NKCC1 inhibitory range, while azosemide is slightly below this range.
EPILEPSY & BEHAVIOR
(2021)
Article
Clinical Neurology
Wolfgang Loescher, Graeme J. Sills, H. Steve White
Summary: Alkyl-carbamates have been developed for the treatment of anxiety and epilepsy since 1955, with varying levels of success. These drugs share the ability to enhance inhibitory neurotransmission through modulation of the GABA(A) receptor, but also have different mechanisms of action and adverse events. Cenobamate stands out for its unique efficacy in treating seizures, but is also associated with serious rash and low tolerability at higher doses, suggesting the need for further safety studies and clinical experience.
Article
Neurosciences
Lisa Welzel, David H. Bergin, Alina Schidlitzki, Friederike Twele, Marie Johne, Pavel Klein, Wolfgang Loescher
Summary: The authors proposed a novel approach involving multiple targets and networks, combining drugs to prevent the onset of epilepsy, and provided initial evidence of its effectiveness.
NEUROBIOLOGY OF DISEASE
(2021)
Editorial Material
Clinical Neurology
Kai Kaila, Wolfgang Loescher
Summary: This article responds to Kevin Staley's critique of our research, explaining that our study was conducted on an asphyxia model, not just hypercarbia; clinically relevant doses of bumetanide lead to significantly lower concentrations in the brain than what is needed for any direct effect on neuronal functions; furthermore, bumetanide's molecular target in the brain has vital functions that make specifically targeting the depolarizing and excitatory actions of gamma-aminobutyric acid in neonatal seizures difficult.
Article
Cell Biology
Birthe Gericke, Inka Wienboeker, Gudrun Brandes, Wolfgang Loescher
Summary: This study investigated the localization and function of P-glycoprotein (Pgp) in intracellular compartments using biochemical and ultrastructural methods. The results showed that Pgp is rarely or not expressed at the limiting membrane of endolysosomes (ELs), but is present in early endosomes and intraluminal vesicles.
Article
Multidisciplinary Sciences
Gaelle Batot, Cameron S. Metcalf, Laura A. Bell, Alberto Pauletti, Karen S. Wilcox, Sonja Broeer
Summary: This study explores the modeling of epilepsy caused by central nervous system (CNS) infection and its use as a platform for testing novel antiseizure compounds. The TMEV infection model in mice replicates the clinical symptoms of viral encephalitis and subsequent epilepsy in humans, and provides a means to investigate the mechanisms of epilepsy development and identify therapeutic targets for patients at risk.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Clinical Neurology
Bjorn Welzel, Ricardo Schmidt, Marie Johne, Wolfgang Loescher
Summary: In a rat model of birth asphyxia, midazolam not only prevented seizures but also reduced neuroinflammation, behavioral and cognitive abnormalities, and neurodegeneration following asphyxia. These findings suggest that midazolam has potential as an intervention to improve the treatment and outcome of birth asphyxia.
ANNALS OF NEUROLOGY
(2023)
Review
Clinical Neurology
Wolfgang Loescher, Carl E. Stafstrom
Summary: Epilepsy is associated with neurobehavioral comorbidities and a bidirectional relationship. Rodent models provide valuable insights into shared mechanisms and potential treatments for epilepsy and its comorbidities.
Article
Clinical Neurology
Chris Rundfeldt, Pavel Klein, Detlev Boison, Alexander Rotenberg, Raimondo D'Ambrosio, Cliff Eastman, Benton Purnell, Madhuvika Murugan, Howard P. Goodkin, Wolfgang Loescher
Summary: This study presents a novel meglumine-based solution of topiramate (TPM) that may be well suited for clinical development. Meglumine significantly enhances the aqueous solubility of TPM and can be used to prepare drug cocktails with other antiseizure medications. Tolerability studies demonstrate excellent tolerability of the novel drug solutions.
Review
Clinical Neurology
Wolfgang Loescher
Summary: Ivermectin is a potent antiparasitic drug, but it is not suitable for the treatment of epilepsy due to its limited penetration into the mammalian brain, non-selective activation of multiple receptors, equivocal preclinical evidence for antiseizure effects, and lack of direct antiseizure effect in clinical studies.
Review
Cell Biology
Wolfgang Loescher, H. Steve White
Summary: In the past 30 years, many new anti-seizure medicines have been developed for epilepsy treatment, but drug-resistant epilepsy (DRE) still affects a significant percentage of patients. Current approaches to discovering new DRE treatments involve testing drugs in preclinical models that show varying degrees of drug resistance. Recent efforts have been made to include more relevant models in the evaluation of investigational drugs, to better understand DRE mechanisms and test new therapies. This review discusses the pharmacology of different epilepsy models and the challenges in identifying novel treatments.
Article
Agriculture, Dairy & Animal Science
Mahtab Bahramsoltani, Sonja Broeer, Susann Langforth, Corinna Eule, Alina Prior, Lena Vogt, Ting-Ting Li, Rebecca Schirone, Alina Pohl, Katharina Charlotte Jensen
Summary: Due to the importance of communication skills in the professional success of veterinarians, there is a focus on developing communication classes in veterinary curricula. At Freie Universitat Berlin, an e-learning course and a practical communication course have been established. The study investigated the impact of these courses on the relevance of veterinary competencies and the self-assessment of communication skills. The findings showed that the practical course had a significant impact on the students' perception of the importance of communicative competencies and their self-assessment of communication skills.
Article
Cell & Tissue Engineering
Marina Bershteyn, Sonja Broer, Mansi Parekh, Yves Maury, Steven Havlicek, Sonja Kriks, Luis Fuentealba, Seonok Lee, Robin Zhou, Geetha Subramanyam, Meliz Sezan, Eric Steven Sevilla, Whitney Blankenberger, Julien Spatazza, Li Zhou, Hubert Nethercott, David Traver, Philip Hampel, Hannah Kim, Michael Watson, Naomi Salter, Anastasia Nesterova, Wai Au, Arnold Kriegstein, Arturo Alvarez-Buylla, John Rubenstein, Gautam Banik, Alessandro Bulfone, Catherine Priest, Cory R. Nicholas
Summary: This study reports a cell therapy alternative for drug-resistant mesial temporal lobe epilepsy (MTLE). The transplantation of inhibitory interneurons derived from human embryonic stem cells effectively suppressed seizures and improved pathological features in a mouse model of chronic MTLE.
Article
Behavioral Sciences
Ricardo Schmidt, Bjorn Welzel, Wolfgang Loescher
Summary: Neonatal seizures are common after birth asphyxia, occurring more frequently in males. Stress and circadian rhythms also affect seizure characteristics.
EPILEPSY & BEHAVIOR
(2023)
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)