Article
Biochemistry & Molecular Biology
Elena Petukhova, Daria Ponomareva, Karin Rustler, Burkhard Koenig, Piotr Bregestovski
Summary: In this study, it was found that Glyght can modulate GABAergic synaptic transmission by acting on extrasynaptic glycine receptors, without affecting postsynaptic GABA receptors and neurotransmitter release mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Segewkal H. Heruye, Ted J. Warren, Joseph A. Kostansek, Samantha B. Draves, Stephanie A. Matthews, Peter J. West, Kristina A. Simeone, Timothy A. Simeone
Summary: Ascorbic acid (AA) plays a crucial role in protecting cells under high oxidative stress, but its effects on synaptic neurotransmission and plasticity under normal conditions have been poorly understood. This study investigated the effects of AA on neurotransmission, plasticity, and network activity in mouse hippocampal slices. The results showed that AA decreased evoked field potentials, inhibited presynaptic fiber volleys, and reduced synaptic plasticity and memory-related activity. These findings suggest that AA plays a significant role in regulating neurotransmission, plasticity, and network activity under normal conditions.
Article
Neurosciences
Giuseppe Talani, Francesca Biggio, Ashish Avinash Gorule, Valentina Licheri, Eleonora Saolini, Daniele Colombo, Gabriele Sarigu, Michele Petrella, Francescangelo Vedele, Giovanni Biggio, Enrico Sanna
Summary: The repeated maternal separation (RMS) model was used to study the long-term effects of early-life stress on brain neurophysiology in mice. The study found significant changes in synaptic transmission and cognitive performance in male mice exposed to RMS. Female mice also showed some changes, but to a lesser extent. Furthermore, the study found that early injection of estrogen prevented the effects of RMS.
Article
Neurosciences
Yi-Ling Lu, Helen E. Scharfman
Summary: Spreading depolarization (SD) is a sudden and synchronous depolarization of principal cells in the brain, followed by neuronal activity depression and slow propagation. Research into SD is often conducted using hippocampal slices triggered by focal stimulation with altered extracellular buffer. The optimized in vitro experimental model described here allows for spontaneous recording of SD without focal stimulation, providing new insights and opportunities for studying SD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Rostislav A. Sokolov, Irina V. Mukhina
Summary: Calcium is a crucial intracellular messenger in the brain that regulates various cell processes. In this study, the researchers used a fluorescent probe to investigate spontaneous Ca2+ events (SCEs) in neurons during culture maturation. They found that SCEs exhibited three different amplitude distributions and were dependent on extracellular Ca2+, neuronal network activity, and specific receptors and channels.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Clinical Neurology
Marie Johne, Christopher Kaeufer, Kerstin Roemermann, Bjoern Gailus, Birthe Gericke, Wolfgang Loescher
Summary: Bumetanide failed to enhance the inhibitory effect of phenobarbital on neonatal seizures, but the combination of DIMAEB and bumepamine showed promising results in suppressing seizures, indicating potential for further development as more effective lead compounds for clinical trials.
Article
Neurosciences
Carlos Perez, Lisa Felix, Simone Durry, Christine R. Rose, Ghanim Ullah
Summary: Spontaneous activity in the neonate forebrain plays a key role in cell maturation and brain development. The fluctuations in intracellular Na+ concentration of neurons and astrocytes are spontaneous, ultraslow, and asynchronous, and not correlated with previously reported synchronous neuronal population bursting or Ca2+ oscillations. These fluctuations disappear after the first postnatal week.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Cell Biology
Taylor E. Huntington, Rahul Srinivasan
Summary: The study revealed unique properties of astrocytic mitochondria in subcellular morphology, mechanisms of calcium influx, and responses to neurotransmitter receptor agonists in the adult mouse brain.
Article
Biochemistry & Molecular Biology
I. Yu Teplov, V. P. Zinchenko, A. M. Kosenkov, S. G. Gaidin, M. N. Nenov, A. Sergeev
Summary: This study investigated the contribution of NMDA and GABA(A) receptors to the shape of spontaneous burst firing in cultured hippocampal neurons. The results show that these receptors effectively modulate burst plateau phase and Ca(2+) transient spikes, impacting action potential amplitudes and firing frequency within a burst. The findings highlight the importance of NMDA and GABA(A) receptors in shaping burst firing in hippocampal neurons.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Carolina Y. Reyes-Soto, Mariana Villaseca-Flores, Enid A. Ovalle-Noguez, Jade Nava-Osorio, Sonia Galvan-Arzate, Edgar Rangel-Lopez, Marisol Maya-Lopez, Socorro Retana-Marquez, Isaac Tunez, Alexey A. Tinkov, Tao Ke, Michael Aschner, Abel Santamaria
Summary: The potential treatment of neurodegenerative disorders requires the development of novel pharmacological strategies. This study found that oleamide can protect mitochondria from neurotoxic substances and has neuroprotective effects.
NEUROTOXICITY RESEARCH
(2022)
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.
Review
Neurosciences
Mari A. Virtanen, Pavel Uvarov, Martina Mavrovic, Jean Christophe Poncer, Kai Kaila
Summary: KCC2 is a multifunctional molecule that can regulate the strength and polarity of GABAergic currents and cytoskeletal dynamics. Its various splice variants play roles in controlling early network events and the formation and plasticity of cortical dendritic spines. The versatility of KCC2 actions is evident in mature neurons during plasticity, disease, and aging, making it one of the most important molecules shaping the overall neuronal phenotype.
TRENDS IN NEUROSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Enni Bertling, Peter Blaesse, Patricia Seja, Elena Kremneva, Gergana Gateva, Mari A. Virtanen, Milla Summanen, Inkeri Spoljaric, Pavel Uvarov, Michael Blaesse, Ville O. Paavilainen, Laszlo Vutskits, Kai Kaila, Pirta Hotulainen, Eva Ruusuvuori
Summary: Intracellular pH is regulated by carbonic anhydrase isoforms CA2 and CA7 in neurons. CA7 interacts with actin, affecting cell morphology, while unique amino acids in CA7 promote actin interaction and influence spine density in neurons.
Review
Clinical Neurology
Wolfgang Loescher, Kai Kaila
Summary: This response corrects the inaccurate descriptions of the model and data in a recent study on the pharmacology of neonatal seizures in a novel rat model of birth asphyxia by Ben-Ari and Delpire. The authors also address the implications of bumetanide actions on neurons in other brain disorders due to its poor brain penetration and wide cellular expression patterns of the target protein NKCC1.
Article
Neurosciences
Philip Hampel, Marie Johne, Bjoern Gailus, Alexandra Vogel, Alina Schidlitzki, Birthe Gericke, Kathrin Toellner, Wiebke Theilmann, Christopher Kaeufer, Kerstin Roemermann, Kai Kaila, Wolfgang Loescher
Summary: The study investigated the effects of NKCC1 expression on seizures and epilepsy using KO and WT mice. Results showed that while NKCC1 deficiency did not affect the induction and progression of epilepsy, it led to a more severe epileptic phenotype.
NEUROBIOLOGY OF DISEASE
(2021)
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
Biochemistry & Molecular Biology
Nikhil J. Pandya, Sonja Meier, Stefka Tyanova, Marco Terrigno, Congwei Wang, A. Mattijs Punt, E. J. Mientjes, Audrey Vautheny, Ben Distel, Thomas Kremer, Ype Elgersma, Ravi Jagasia
Summary: This study investigates the mechanisms and potential therapeutic options for Angelman syndrome. Proteomics analysis reveals changes in protein pathways during different stages of development in an AS mouse model. Restoring UBE3A expression is shown to reverse these changes and provide a promising treatment option. Additionally, a novel UBE3A substrate is discovered, and a protein database is created to support future research.
MOLECULAR PSYCHIATRY
(2022)
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
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.
Meeting Abstract
Clinical Neurology
Bjoern Gailus, Hannah Naundorf, Lisa Welzel, Marie Johne, Kerstin Roemermann, Kai Kaila, Wolfgang Loescher