keyword
https://read.qxmd.com/read/38522998/swimming-short-fibrous-nasal-drops-achieving-intraventricular-administration
#21
JOURNAL ARTICLE
Juan Wang, Qiuyun Wang, Yifei Fu, Min Lu, Liang Chen, Zhiheng Liu, Xiaohan Fu, Xiyu Du, Buwei Yu, Han Lu, Wenguo Cui
Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance...
March 6, 2024: Science Bulletin
https://read.qxmd.com/read/38520864/neuroprotective-effects-of-the-salidroside-derivative-shpl-49-via-the-bdnf-trkb-gap43-pathway-in-rats-with-cerebral-ischemia
#22
JOURNAL ARTICLE
Suxin You, Zhouyun Ma, Pei Zhang, Wenwen Xu, Changsen Zhan, Nina Sang, Jiazhen Xu, Feiyun Wang, Jiange Zhang
Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia...
March 22, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38520800/multiscale-neuro-inspired-models-for-interpretation-of-eeg-signals-in-patients-with-epilepsy
#23
JOURNAL ARTICLE
Fabrice Wendling, Elif Koksal-Ersoz, Mariam Al-Harrach, Maxime Yochum, Isabelle Merlet, Giulio Ruffini, Fabrice Bartolomei, Pascal Benquet
OBJECTIVE: The aim is to gain insight into the pathophysiological mechanisms underlying interictal epileptiform discharges observed in electroencephalographic (EEG) and stereo-EEG (SEEG, depth electrodes) recordings performed during pre-surgical evaluation of patients with drug-resistant epilepsy. METHODS: We developed novel neuro-inspired computational models of the human cerebral cortex at three different levels of description: i) microscale (detailed neuron models), ii) mesoscale (neuronal mass models) and iii) macroscale (whole brain models)...
March 16, 2024: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://read.qxmd.com/read/38520637/binary-nano-inhalant-formulation-of-icariin-enhances-cognitive-function-in-vascular-dementia-via-bdnf-trkb-signaling-and-anti-inflammatory-effects
#24
JOURNAL ARTICLE
Tieshu Li, Shuling Li, Yin Xiong, Xinxin Li, Chun Ma, Zhiying Guan, Lihua Yang
Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution...
March 23, 2024: Neurochemical Research
https://read.qxmd.com/read/38519640/genetic-contribution-to-microglial-activation-in-schizophrenia
#25
JOURNAL ARTICLE
Marja Koskuvi, Elina Pörsti, Tristen Hewitt, Noora Räsänen, Ying-Chieh Wu, Kalevi Trontti, Amanda McQuade, Shringaa Kalyanaraman, Ilkka Ojansuu, Olli Vaurio, Tyrone D Cannon, Jouko Lönnqvist, Sebastian Therman, Jaana Suvisaari, Jaakko Kaprio, Mathew Blurton-Jones, Iiris Hovatta, Markku Lähteenvuo, Taisia Rolova, Šárka Lehtonen, Jari Tiihonen, Jari Koistinaho
Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied...
March 22, 2024: Molecular Psychiatry
https://read.qxmd.com/read/38519181/prebiotics-modulate-the-microbiota-gut-brain-axis-and-ameliorate-anxiety-and-depression-like-behavior-in-hfd-fed-mice
#26
JOURNAL ARTICLE
Igor Henrique Rodrigues de Paiva, Laís Macedo Maciel, Rodrigo Soares da Silva, Ingrid Prata Mendonça, José Roberto Botelho de Souza, Christina Alves Peixoto
Previous research has demonstrated that Prebiotics can influence the composition of the gut microbiota, consequently impacting mood regulation. This study aimed to assess the effects of Prebiotics, specifically Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on neuroinflammation, depression, and anxiety-like behavior in a mouse model fed a high-fat diet (HFD). Initially, mice were divided into two groups: a control group on a standard diet (n = 15) and a group on an HFD for 18 weeks (n = 45)...
April 2024: Food Research International
https://read.qxmd.com/read/38519095/synaptic-electrophysiology-of-the-drosophila-neuromuscular-junction
#27
JOURNAL ARTICLE
Bing Zhang, Bryan Stewart
Chemical synaptic transmission is an important means of neuronal communication in the nervous system. Upon the arrival of an action potential, the nerve terminal experiences an influx of calcium ions, which in turn trigger the exocytosis of synaptic vesicles (SVs) and the release of neurotransmitters into the synaptic cleft. Transmitters elicit synaptic responses in the postsynaptic cell by binding to and activating specific receptors. This is followed by the recycling of SVs at presynaptic terminals. The Drosophila larval neuromuscular junction (NMJ) shares many structural and functional similarities to synapses in other animals, including humans...
March 22, 2024: Cold Spring Harbor Protocols
https://read.qxmd.com/read/38519094/focal-recording-of-synaptic-currents-from-single-boutons-at-the-drosophila-larval-neuromuscular-junction
#28
JOURNAL ARTICLE
Bing Zhang, Bryan Stewart
Focal recording is an extracellular method for studying synaptic transmission at the Drosophila larval neuromuscular junction (NMJ) designed for the study of synaptic activity of one or a few synaptic boutons rather than the ensemble activity of all the boutons as occurs with intracellular recording or two-electrode voltage-clamp. This is a useful technique for investigating the properties of different motor neurons that innervate the same muscle, applying statistical analysis to discrete synaptic events, and investigating the heterogeneity of synaptic release properties among boutons...
March 22, 2024: Cold Spring Harbor Protocols
https://read.qxmd.com/read/38518928/fused-thiophene-as-a-privileged-scaffold-a-review-on-anti-alzheimer-s-disease-potentials-via-targeting-cholinesterases-monoamine-oxidases-glycogen-synthase-kinase-3-and-a%C3%AE-aggregation
#29
REVIEW
Asmaa E Kassab, Ehab M Gedawy, Alaa S Sayed
As a "silent threat," Alzheimer's disease (AD) is quickly rising to the top of the list of costly and troublesome diseases facing humanity. It is growing to be one of the most troublesome and expensive conditions, with annual health care costs higher than those of cancer and comparable to those of cardiovascular disorders. One of the main pathogenic characteristics of AD is the deficiency of the neurotransmitter acetylcholine (ACh) which plays a vital role in memory, learning, and attention. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in hydrolyzing ACh...
March 20, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38515445/safety-tolerability-and-efficacy-estimate-of-evoked-gamma-oscillation-in-mild-to-moderate-alzheimer-s-disease
#30
JOURNAL ARTICLE
Mihály Hajós, Alyssa Boasso, Evan Hempel, Monika Shpokayte, Alex Konisky, Chandran V Seshagiri, Vitella Fomenko, Kim Kwan, Jessie Nicodemus-Johnson, Suzanne Hendrix, Brent Vaughan, Ralph Kern, Jonathan T Megerian, Zach Malchano
BACKGROUND: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models...
2024: Frontiers in Neurology
https://read.qxmd.com/read/38514619/the-ampk-related-kinase-nuak1-controls-cortical-axons-branching-by-locally-modulating-mitochondrial-metabolic-functions
#31
JOURNAL ARTICLE
Marine Lanfranchi, Sozerko Yandiev, Géraldine Meyer-Dilhet, Salma Ellouze, Martijn Kerkhofs, Raphael Dos Reis, Audrey Garcia, Camille Blondet, Alizée Amar, Anita Kneppers, Hélène Polvèche, Damien Plassard, Marc Foretz, Benoit Viollet, Kei Sakamoto, Rémi Mounier, Cyril F Bourgeois, Olivier Raineteau, Evelyne Goillot, Julien Courchet
The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons...
March 21, 2024: Nature Communications
https://read.qxmd.com/read/38513663/transport-mechanism-and-pharmacology-of-the-human-glyt1
#32
JOURNAL ARTICLE
Yiqing Wei, Renjie Li, Yufei Meng, Tuo Hu, Jun Zhao, Yiwei Gao, Qinru Bai, Na Li, Yan Zhao
The glycine transporter 1 (GlyT1) plays a crucial role in the regulation of both inhibitory and excitatory neurotransmission by removing glycine from the synaptic cleft. Given its close association with glutamate/glycine co-activated NMDA receptors (NMDARs), GlyT1 has emerged as a central target for the treatment of schizophrenia, which is often linked to hypofunctional NMDARs. Here, we report the cryo-EM structures of GlyT1 bound with substrate glycine and drugs ALX-5407, SSR504734, and PF-03463275. These structures, captured at three fundamental states of the transport cycle-outward-facing, occluded, and inward-facing-enable us to illustrate a comprehensive blueprint of the conformational change associated with glycine reuptake...
March 13, 2024: Cell
https://read.qxmd.com/read/38513140/pd1-inhibits-pkc%C3%AE-dependent-phosphorylation-of-cytoskeleton-related-proteins-and-immune-synapse-formation
#33
JOURNAL ARTICLE
Daniela Chmiest, Silvia Podavini, Kalliopi Ioannidou, David Vallois, Chantal Décaillet, Montserrat Gonzalez, Manfredo Quadroni, Kevin Blackney, Rebekka Schairer, Laurence L de Leval, Margot Thome
The inhibitory cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with PKC theta (PKCof a variety of cytoskeleton-related proteins...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513002/motor-unit-modes-in-the-calf-muscles-during-a-submaximal-isometric-contraction-are-changed-by-brief-stretches
#34
JOURNAL ARTICLE
Logan E Weinman, Alessandro Del Vecchio, Melissa R Mazzo, Roger M Enoka
The purpose of our study was to investigate the influence of a stretch intervention on the common modulation of discharge rate among motor units in the calf muscles during a submaximal isometric contraction. The current report comprises a computational analysis of a motor unit dataset that we published previously (Mazzo et al., 2021). Motor unit activity was recorded from the three main plantar flexor muscles while participants performed an isometric contraction at 10% of the maximal voluntary contraction force before and after each of two interventions...
March 21, 2024: Journal of Physiology
https://read.qxmd.com/read/38512854/the-chd-family-chromatin-remodeling-enzyme-kismet-promotes-both-clathrin-mediated-and-activity-dependent-bulk-endocytosis
#35
JOURNAL ARTICLE
Emily L Hendricks, Faith L W Liebl
Chromodomain helicase DNA binding domain (CHD) proteins, including CHD7 and CHD8, remodel chromatin to enable transcriptional programs. Both proteins are important for proper neural development as heterozygous mutations in Chd7 and Chd8 are causative for CHARGE syndrome and correlated with autism spectrum disorders, respectively. Their roles in mature neurons are poorly understood despite influencing the expression of genes required for cell adhesion, neurotransmission, and synaptic plasticity. The Drosophila homolog of CHD7 and CHD8, Kismet (Kis), promotes neurotransmission, endocytosis, and larval locomotion...
2024: PloS One
https://read.qxmd.com/read/38512693/a-mean-field-model-of-gamma-frequency-oscillations-in-networks-of-excitatory-and-inhibitory-neurons
#36
JOURNAL ARTICLE
Farzin Tahvili, Alain Destexhe
Gamma oscillations are widely seen in the cerebral cortex in different states of the wake-sleep cycle and are thought to play a role in sensory processing and cognition. Here, we study the emergence of gamma oscillations at two levels, in networks of spiking neurons, and a mean-field model. At the network level, we consider two different mechanisms to generate gamma oscillations and show that they are best seen if one takes into account the synaptic delay between neurons. At the mean-field level, we show that, by introducing delays, the mean-field can also produce gamma oscillations...
March 21, 2024: Journal of Computational Neuroscience
https://read.qxmd.com/read/38512688/cultivation-differentiation-and-lentiviral-transduction-of-human-induced-pluripotent-stem-cell-hipsc-derived-glutamatergic-neurons-for-studying-human-tau
#37
JOURNAL ARTICLE
Sarah Buchholz, Michael Bell-Simons, Cagla Cakmak, Jennifer Klimek, Li Gan, Hans Zempel
Tau pathology is a major hallmark of many neurodegenerative diseases summarized under the term tauopathies. In most of these disorders,  such as Alzheimer's disease, the neuronal axonal microtubule-binding Tau protein becomes mislocalized to the somatodendritic compartment. In human disease, this missorting of Tau is accompanied by an abnormally high phosphorylation state of the Tau protein, and several downstream pathological consequences (e.g., loss of microtubules, degradation of postsynaptic spines, impaired synaptic transmission, neuronal death)...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512666/tau-oligomers-as-pathogenic-seeds-preparation-characterization-and-propagation-in-vitro-and-in-vivo
#38
JOURNAL ARTICLE
Urmi Sengupta, Rakez Kayed
Tau oligomers have been shown to be the main toxic tau species in several neurodegenerative disorders. To study tau oligomers, we have developed reagents and established methods for the reliable preparation, isolation, and detection of tau oligomers as well as their seeding and propagation both in vitro and in vivo. Detailed below are methods for isolation of tau oligomers from brain tissues and detection of tau oligomers using tau oligomer-specific antibodies by biochemical, immunohistochemical, and biophysical methods...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512439/aqp4-endocytosis-lysosome-degradation-mediated-by-mmp-9-%C3%AE-dg-involved-in-diabetes-cognitive-impairment
#39
JOURNAL ARTICLE
Ye Yuan, Wei Peng, Jingna Lei, Yi Zhao, Beiyu Zhao, Yan Li, Jin Wang, Qiumin Qu
Cognitive impairment is considered to be one of the important comorbidities of diabetes, but the underlying mechanisms are widely unknown. Aquaporin-4 (AQP4) is the most abundant water channel in the central nervous system, which plays a neuroprotective role in various neurological diseases by maintaining the function of glymphatic system and synaptic plasticity. However, whether AQP4 is involved in diabetes-related cognitive impairment remains unknown. β-dystroglycan (β-DG), a key molecule for anchoring AQP4 on the plasma membrane of astrocytes and avoiding its targeting to lysosomes for degradation, can be cleaved by matrix metalloproteinase-9 (MMP-9)...
March 21, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38511765/neurogenomic-landscape-associated-with-status-dependent-cooperative-behaviour
#40
JOURNAL ARTICLE
Peri E Bolton, T Brandt Ryder, Roslyn Dakin, Jennifer L Houtz, Ignacio T Moore, Christopher N Balakrishnan, Brent M Horton
The neurogenomic mechanisms mediating male-male reproductive cooperative behaviours remain unknown. We leveraged extensive transcriptomic and behavioural data on a neotropical bird species (Pipra filicauda) that performs cooperative courtship displays to understand these mechanisms. In this species, the cooperative display is modulated by testosterone, which promotes cooperation in non-territorial birds, but suppresses cooperation in territory holders. We sought to understand the neurogenomic underpinnings of three related traits: social status, cooperative display behaviour and testosterone phenotype...
March 21, 2024: Molecular Ecology
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