Article
Cell Biology
Anna Antoniou, Loic Auderset, Lalit Kaurani, Eva Sebastian, Yuzhou Zeng, Maria Allahham, Silvia Cases-Cunillera, Susanne Schoch, Jan Gruendemann, Andre Fischer, Anja Schneider
Summary: Extracellular vesicles (EVs) play a role in cellular communication through the delivery of microRNAs (miRNAs) that regulate gene expression. This study demonstrates that brain-derived neurotrophic factor (BDNF) facilitates the sorting and delivery of specific miRNAs in neuron-derived EVs, leading to increased excitatory synapse formation and synaptic transmission. The differential expression of genes related to development and synaptogenesis, predicted targets of these miRNAs, further supports their role in modulating neural circuit connectivity. These findings contribute to a better understanding of neuropsychiatric disorders associated with aberrant neural circuitry.
Article
Neurosciences
Sabine C. Konings, Laura Torres-Garcia, Isak Martinsson, Gunnar K. Gouras
Summary: Synaptic changes and neuronal network dysfunction are early features of Alzheimer's disease. Apolipoprotein E4 (ApoE4) is a major genetic risk factor in AD and can induce hyperexcitability in vulnerable brain regions. ApoE is mainly produced by astrocytes, but neurons can also produce it under stress conditions. This study found that ApoE isoforms from different cellular sources can target synapses and have differential effects on neuronal activity.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Antonios M. Diab, Michael Wigerius, Dylan P. Quinn, Jiansong Qi, Ibrahim Shahin, Julia Paffile, Kavita Krueger, Barbara Karten, Stefan R. Krueger, James P. Fawcett
Summary: This study reveals that male mice lacking NCK1 have impairments in short-term and working memory, as well as spatial learning. Additionally, female mice deficient in NCK1 show memory impairment in reversal learning. NCK1 contributes to hippocampal-dependent memory by stabilizing actin dynamics and dendritic formation.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Neurosciences
Christophe Mulle, Valerie Crepel
Summary: Kainate receptors (KARs) are ionotropic glutamate receptors that play important physiological roles in neuronal circuits, regulating EPSCs as post-synaptic receptors and controlling ion channels through non-canonical metabotropic actions. KARs, activated by endogenous glutamate, modulate neuronal circuit activity and plasticity under normal physiological conditions.
Article
Biology
Xinrui L. Zhang, William C. Spencer, Nobuko Tabuchi, Meagan M. Kitt, Evan S. Deneris, Paschalis Kratsios
Summary: The assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. The study shows that unique distal enhancers define the Pet1 neuron lineage that generates serotonin neurons in mice. Pet1 and Lmx1b control chromatin accessibility to select Pet1-lineage-specific enhancers for serotonin neurotransmission.
Review
Neurosciences
Weidong Feng, Yinan Li, Paschalis Kratsios
Summary: Animal nervous systems are characterized by a diverse range of cell types. Previous research has shed light on the early stages of neuronal development, including neuronal migration and axodendritic patterning, but little is known about the mechanisms controlling later steps of development. Recent studies in Caenorhabditis elegans, Drosophila melanogaster, and mice suggest that Hox proteins, a family of homeodomain transcription factors, play new roles in processes occurring during later stages of neuronal development, such as synapse formation and acquisition of neuronal terminal identity features. Furthermore, these studies provide evidence that Hox proteins are required to maintain synaptic structures and neuronal terminal identity throughout post-embryonic life, expanding their functional repertoire beyond the control of early patterning.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Katarzyna M. Grochowska, Marit Sperveslage, Rajeev Raman, Antonio V. Failla, Dawid Glow, Christian Schulze, Laura Laprell, Boris Fehse, Michael R. Kreutz
Summary: The complex morphology of neurons presents a challenge for proteostasis, but recent studies have shown that mature lysosomes can be found in dendrites and release their content through fusion with the plasma membrane. These dendritic lysosomes are heterogeneous in composition and only those containing LAMP2A and LAMP2B exhibit activity-dependent motility. They dock near NMDAR receptors via an association with SAP102/Dlg3, and NMDAR activation decreases lysosome motility and promotes fusion with the membrane. Chaperone-mediated autophagy supplies content that is released through lysosome exocytosis, enabling local disposal of aggregation-prone proteins.
Article
Biochemistry & Molecular Biology
Matthew J. Sticco, Perla A. Pena Palomino, David Lukacsovich, Brianna L. Thompson, Csaba Foeldy, Susanne Ressl, David C. Martinelli
Summary: Synapses are the key structures through which neurons communicate, regulated by a variety of proteins. C1QL proteins, part of the C1q superfamily, act as synaptic organizers involved in crucial neuronal processes. The study shows that C1QL3 mediates a novel cell-cell adhesion complex involving ADGRB3 and two neuronal pentraxins, suggesting the formation of a new trans-synaptic adhesion complex.
Article
Neurosciences
Harrison J. Ramsay, Sara E. Gookin, Austin M. Ramsey, Dean J. Kareemo, Kevin C. Crosby, Dominik G. Stich, Samantha S. Olah, Hannah S. Actor-Engel, Katharine R. Smith, Matthew J. Kennedy
Summary: Postsynaptic neurotransmitter receptors and their associated scaffolding proteins form nanometer-scale subsynaptic domains (SSDs) within the postsynaptic membrane. The role of neurotransmitter signaling in the initial assembly of these SSDs during synapse development is still unknown.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Sven Wagner, ChoongKu Lee, Lucia Rojas, Christian G. Specht, JeongSeop Rhee, Nils Brose, Theofilos Papadopoulos
Summary: This study has identified the important role of GABA(A)R-alpha 3 in promoting Gephyrin-mediated and CB-independent formation of inhibitory postsynapses. It suggests that other proteins interacting with Gephyrin, besides CB, may also play a role in the formation of inhibitory synapses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Leticia Perez-Sisques, Laia Sitja-Roqueta, Melike Kucukerden, Ana Gamez-Valero, Albert Coll-Manzano, Eulalia Marti, Esther Perez-Navarro, Jordi Alberch, Jordi Soriano, Merce Masana, Cristina Malagelada
Summary: Extracellular vesicles, specifically neuron-derived EVs, play a crucial role in intercellular communication within the central nervous system. These EVs carry signaling molecules and exert a trophic effect on neurons, influencing synaptic events and promoting neuronal protection.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Biochemistry & Molecular Biology
Shanu George, John Bear, Michael J. Taylor, Karthik Kanamalla, Christopher D. Fekete, Tzu-Ting Chiou, Celia P. Miralles, Theofilos Papadopoulos, Angel L. De Blas
Summary: Collybistin (CB) is a guanine nucleotide exchange factor selectively localized at GABAergic and glycinergic postsynapses. Different isoforms of collybistin are expressed in the brain, with CBSH3- protein playing a significant role in the regulation of the size of GABAergic postsynapse clusters, particularly in parvalbumin positive interneurons. The lack of CBSH3- expression is an important issue because it has a strong effect in promoting the postsynaptic clustering of gephyrin and GABA-A receptors.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Chase M. Barker, Kaleb D. Miles, Caleb A. Doll
Summary: Motor behavior requires the balanced production and integration of various types of neural cells. Individuals with Fragile X syndrome and associated autism spectrum disorders often have significant motor challenges. This study demonstrates that Fmrp regulates the formation of specific interneurons and motor neurons, which could influence the formation and function of motor circuits.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Jian Liang, L. H. Dennis Kruijssen, C. J. Aniek Verschuuren, J. B. Bas Voesenek, F. W. Feline Benavides, Maria Saez Gonzalez, Marvin Ruiter, J. Corette Wierenga
Summary: The study demonstrates that inhibitory synapse formation and stabilization in hippocampal organotypic slices is mediated by CB1 receptor activation and involves unconventional downstream pathways. Neuronal activity is not required for inhibitory bouton formation, which can be induced by elevating cAMP levels and activating Gs-proteins. Inhibition of PKA activity prevents the CB1 receptor-mediated formation of inhibitory boutons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Carla Sanchez-Castillo, Maria Cuartero, Alba Fernandez-Rodrigo, Victor Briz, Sergio Lopez-Garcia, Raquel Jimenez-Sanchez, Juan A. Lopez, Mariona Graupera, Jose A. Esteban
Summary: Neuronal connectivity and synaptic plasticity are essential for brain function. Phosphatidylinositol 3-kinase (PI3K) signaling plays a crucial role in neuronal growth and synaptic plasticity. This study demonstrates that the two major isoforms of PI3K, p110 alpha and p110 beta, have distinct functions in dendritic and postsynaptic structures, neurotransmitter release, and long-term potentiation.
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
Clinical Neurology
Tommi Ala-Kurikka, Alexey Pospelov, Milla Summanen, Aleksander Alafuzoff, Samu Kurki, Juha Voipio, Kai Kaila
Summary: A rat model of birth asphyxia was developed to mimic clinical cases, showing that seizures are triggered after exposure to hypoxia, rather than during the insult.
Article
Critical Care Medicine
Jesse S. Shapiro, Stephen Hearps, Vanessa C. Rausa, Vicki Anderson, Nicholas Anderson, Remy Pugh, Tracey Chau, Cathriona Clarke, Gavin A. Davis, Fabian Fabiano, Feiven Fan, Georgia M. Parkin, Michael Takagi, Franz E. Babl
Summary: This study confirmed that the SCAT5 and Child SCAT5 memory components are valid measures of memory in concussed children.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Sport Sciences
Franz E. Babl, Vicki Anderson, Vanessa C. Rausa, Nicholas Anderson, Remy Pugh, Tracey Chau, Cathriona Clarke, Fabian Fabiano, Feiven Fan, Stephen Hearps, Georgia Parkin, Michael Takagi, Gavin Davis
Summary: The study found that both SCAT5 and ChildSCAT5 are effective in distinguishing between children with and without concussion, with the concussion group reporting a higher number and severity of symptoms compared to controls. Acceptable levels of between-group discrimination were identified for certain components of the assessment tools.
INTERNATIONAL JOURNAL OF SPORTS MEDICINE
(2022)
Article
Biochemical Research Methods
Loic Duffet, Seher Kosar, Mariangela Panniello, Bianca Viberti, Edward Bracey, Anna D. Zych, Arthur Radoux-Mergault, Xuehan Zhou, Jan Dernic, Luca Ravotto, Yuan-Chen Tsai, Marta Figueiredo, Shiva K. Tyagarajan, Bruno Weber, Miriam Stoeber, Nadine Gogolla, Markus H. Schmidt, Antoine R. Adamantidis, Tommaso Fellin, Denis Burdakov, Tommaso Patriarchi
Summary: This study developed a genetically encoded orexin sensor called OxLight1, which enables sensitive and direct optical detection of orexin neuropeptides in living animals with high spatiotemporal resolution. The sensor was used in mouse experiments to show that orexin release is associated with behaviors such as running, stress, and sleep-to-wake transitions.
Article
Biochemistry & Molecular Biology
Krisztina Toth, Nikolett Lenart, Peter Berki, Rebeka Fekete, Eszter Szabadits, Balazs Posfai, Csaba Cserep, Ahmad Alatshan, Szilvia Benko, Daniel Kiss, Christian A. Huebner, Attila Gulyas, Kai Kaila, Zsuzsanna Koernyei, Adam Denes
Summary: The NKCC1 ion transporter has an important role in microglia, the main inflammatory cells of the brain, by regulating cellular morphology, volume changes, and inflammatory responses. Microglial NKCC1 deficiency leads to exaggerated inflammation and worsened neurological outcomes.
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
Neurosciences
Wolfgang Loescher, Kai Kaila
Summary: Current NKCC1 inhibitors like bumetanide have limited penetration into the CNS, leading to the need for further research to develop brain-permeant compounds that are selective for NKCC1. Another challenge is to understand the effects of these drugs on different NKCC1-expressing cellular targets within and outside the brain parenchyma.
Article
Physiology
Iwona Olejniczak, Benjamin Campbell, Yuan-Chen Tsai, Shiva K. Tyagarajan, Urs Albrecht, Jurgen A. Ripperger
Summary: The process of searching for food in mammals is well-organized and follows a decision-making process based on necessity. Scavenging is preferred during their active phase. Previous studies have identified various time-dependent regulatory processes originating from the suprachiasmatic nuclei (SCN), which convert external light information into synchronizing output signals. This study revisits the function of the SCN in influencing the timing of food searching in mice and finds that it is independent of light but modified by the palatability of the food source.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Samu N. Kurki, Pavel Uvarov, Alexey S. Pospelov, Kalevi Trontti, Antje K. Huebner, Rakenduvadhana Srinivasan, Masahiko Watanabe, Iiris Hovatta, Christian A. Huebner, Kai Kaila, Mari A. Virtanen
Summary: The widely expressed Na-K-2Cl cotransporter NKCC1 has been hindered in its understanding of its roles in brain functions and disorders due to lack of reliable data on its developmental and (sub)cellular expression patterns. This study provides a well-controlled analysis of NKCC1 protein expression in different cell types of the mouse brain and reveals its high levels in oligodendrocytes, differential expression in neurons, microglia, astrocytes, developing pericytes, and progenitor cells of the dentate gyrus, and the presence of NKCC1 splice variants. These findings contribute to our understanding of NKCC1 functions in the brain and have implications for the development of neuron-targeting NKCC1-blockers.
Article
Neurosciences
Robert J. Hatch, Geza Berecki, Nikola Jancovski, Melody Li, Ben Rollo, Paymaan Jafar-Nejad, Frank Rigo, Kai Kaila, Christopher A. Reid, Steven Petrou
Summary: Brain pH plays a critical role in determining neuronal activity, with alkalosis increasing excitability and acidosis reducing it. This study investigates the molecular mechanisms behind the seizure protection observed when brain pH shifts through the inhalation of carbogen. The findings suggest that acidification reduces excitability in excitatory neurons but has no effect on inhibitory neurons, providing insight into the basis of seizure suppression caused by carbogen-mediated acidification.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
James Fasham, Antje K. Huebner, Lutz Liebmann, Reham Khalaf-Nazzal, Reza Maroofian, Nderim Kryeziu, Saskia B. Wortmann, Joseph S. Leslie, Nishanka Ubeyratna, Grazia M. S. Mancini, Marjon van Slegtenhorst, Martina Wilke, Tobias B. Haack, Hanan E. Shamseldin, Joseph G. Gleeson, Mohamed Almuhaizea, Imad Dweikat, Bassam Abu-Libdeh, Muhannad Daana, Maha S. Zaki, Matthew N. Wakeling, Lucy McGavin, Peter D. Turnpenny, Fowzan S. Alkuraya, Henry Houlden, Peter Schlattmann, Kai Kaila, Andrew H. Crosby, Emma L. Baple, Christian A. Huebner
Summary: A novel neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 has been identified, which exhibits learning difficulties, seizures, and characteristic brain imaging features. Dysfunction of GABAergic transmission may contribute to the disorder.
Article
Immunology
Samu N. Kurki, Tommi Ala-Kurikka, Arto Lipponen, Alexey S. Pospelov, Taisia Rolova, Jari Koistinaho, Juha Voipio, Kai Kaila
Summary: Systemic inflammation induces both protective and pro-inflammatory responses in the brain, leading to disrupted cognition. The mechanisms underlying the peripheral-central inflammatory signaling are not fully understood.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Cell Biology
Samu N. Kurki, Rakenduvadhana Srinivasan, Jens Laine, Mari A. Virtanen, Tommi Ala-Kurikka, Juha Voipio, Kai Kaila
Summary: Acute neuroinflammation leads to hyperexcitability in dentate gyrus (DG) neurons, caused by disruption of neuronal chloride regulation and loss of GABAergic inhibition, resulting in cognitive impairment.
Article
Geriatrics & Gerontology
Georgia M. Parkin, Soyun Kim, Abanoub Mikhail, Rond Malhas, Liv McMillan, Martina Hollearn, Douglas A. Granger, Mark Mapstone, Michael A. Yassa, Elizabeth A. Thomas
Summary: This study found that inflammatory markers in saliva are associated with those found in circulation, suggesting shared inflammatory mechanisms between these two fluids. The higher levels of cytokines measured in saliva suggest that it might represent a better peripheral fluid to gauge inflammatory processes. Additionally, the research revealed robust sex differences in several salivary cytokines, indicating potential implications for their use as disease biomarkers in the elderly and their association with sex differences in the prevalence of age-related conditions.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2023)