African mole-rats (Bathyergidae, Rodentia) are subterranean rodents that live in extensive dark underground tunnel systems and rarely emerge aboveground. They can discriminate between light and dark but show no overt visually driven behaviours except for light-avoidance responses. Their eyes and central visual system are strongly reduced but not degenerated. Here, we focus on retinal ganglion cells (RGCs). Sighted mammals have numerous RGC types with distinct morphological and functional properties that encode different aspects of a visual scene. We analysed the morphological diversity of 216 intracellularly dye-injected RGCs in the giant mole-rat (Fukomys mechowii) and 48 RGCs in Ansell's mole-rat (Fukomys anselli). Using a hierarchical cluster analysis on 11 morphological parameters, we show that both species possess at least five RGC types with distinct dendritic field sizes and branching patterns. These resemble some RGC types of the mouse and rat, but mole-rat RGCs feature overall sparser and more asymmetric branching patterns. The dendritic trees of most RGCs in all clusters are monostratified in the inner plexiform layer, but bistratified and multistratified/diffuse cells also exist. Thus, although RGC morphologies have become disorganized, the basic retinal organization principle of parallel information processing by distinct RGC types is retained.

• Klíčová slova
• Fukomys, microphthalmia, mole-rats, ocular regression, retinal ganglion cells, subterranean mammals,
• MeSH
• dendrity fyziologie   MeSH
• mikroftalmičtí podzemní hlodavci * fyziologie   anatomie a histologie   MeSH
• retinální gangliové buňky * fyziologie   cytologie   MeSH
• shluková analýza MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Microtubule (MT) and F-actin cytoskeletal cross-talk and organization are important aspects of axon guidance mechanisms, but how associated proteins facilitate this function remains largely unknown. While the MT-associated protein, CKAP5 (XMAP215/ch-TOG), has been best characterized as a MT polymerase, we have recently highlighted a novel role for CKAP5 in facilitating interactions between MT and F-actin in vitro and in embryonic Xenopus laevis neuronal growth cones. However, the mechanism by which it does so is unclear. Here, using in vitro reconstitution assays coupled with total internal reflection fluorescence microscopy, we report that the TOG5 domain of CKAP5 is necessary for its ability to bind to and bundle actin filaments, as well as to cross-link MTs and F-actin in vitro. Additionally, we show that this novel MT/F-actin cross-linking function of CKAP5 is possible even in MT polymerase-incompetent mutants of CKAP5 in vivo. Indeed, CKAP5 requires both MT and F-actin binding, but not MT polymerization, to promote MT-F-actin alignment in growth cones and axon outgrowth. Taken together, our findings provide mechanistic insights into how MT populations penetrate the growth cone periphery through CKAP5-facilitated interaction with F-actin during axon outgrowth and guidance.

• MeSH
• aktiny * metabolismus   MeSH
• axony metabolismus   MeSH
• mikrofilamenta * metabolismus   MeSH
• mikrotubuly * metabolismus   MeSH
• neurony * metabolismus   MeSH
• proteinové domény MeSH
• proteiny asociované s mikrotubuly * metabolismus   MeSH
• proteiny Xenopus * metabolismus   MeSH
• růstové kužele * metabolismus   MeSH
• vazba proteinů MeSH
• Xenopus laevis * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktiny * MeSH
• CKAP5 protein, Xenopus MeSH Prohlížeč
• proteiny asociované s mikrotubuly * MeSH
• proteiny Xenopus * MeSH

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.

• Klíčová slova
• Anti-NMDAR encephalitis, BDNF, Dendritic branching, Neuronal development, Synaptic proteins,
• MeSH
• dendrity * účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• membránové proteiny metabolismus   imunologie   MeSH
• mozkový neurotrofický faktor * metabolismus   MeSH
• neurony * metabolismus   účinky léků   MeSH
• protein PSD-95 metabolismus   MeSH
• proteiny nervové tkáně imunologie   metabolismus   MeSH
• receptory N-methyl-D-aspartátu * imunologie   MeSH
• synaptofysin metabolismus   MeSH
• transportní proteiny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gephyrin MeSH Prohlížeč
• membránové proteiny MeSH
• mozkový neurotrofický faktor * MeSH
• protein PSD-95 MeSH
• proteiny nervové tkáně MeSH
• receptory N-methyl-D-aspartátu * MeSH
• synaptofysin MeSH
• transportní proteiny MeSH

Endogenous neurosteroids (NS) and their synthetic analogs, neuroactive steroids (NAS), are potentially useful drug-like compounds affecting the pathophysiology of miscellaneous central nervous system disorders (e.g. Alzheimer´s disease, epilepsy, depression, etc.). Additionally, NS have been shown to promote neuron viability and neurite outgrowth upon injury. The molecular, structural and physicochemical basis of the NS effect on neurons is so far not fully understood, and the development of new, biologically relevant assays is essential for their comparative analysis and for assessment of their mechanism of action. Here, we report the development of a novel, plate-based, high-content in vitro assay for screening of NS and newly synthesized, 5β-reduced NAS for the promotion of postnatal neuron survival and neurite growth using fluorescent, postnatal mixed cortical neuron cultures isolated from thy1-YFP transgenic mice. The screen allows a detailed time course analysis of different parameters, such as the number of neurons or neurite lengths of 7-day, in vitro neuron cultures. Using the screen, we identify a new NAS, compound 42, that promotes the survival and growth of postnatal neurons significantly better than several endogenous NS (dehydroepiandrosterone, progesterone, and allopregnanolone). Interestingly, we demonstrate that compound 42 also promotes the proliferation of glia (in particular oligodendrocytes) and that the glial function is critical for its neuron growth support. Computational analysis of the biological data and calculated physicochemical properties of tested NS and NAS demonstrated that their biological activity is proportional to their lipophilicity. Together, the screen proves useful for the selection of neuron-active NAS and the comparative evaluation of their biologically relevant structural and physicochemical features.

• Klíčová slova
• Computational analysis, High-content screening, Myelin basic protein, Neurite growth, Neuroactive steroids, Neurosteroids,
• MeSH
• myši transgenní MeSH
• myši MeSH
• neurity MeSH
• neurony MeSH
• neurosteroidy * MeSH
• oligodendroglie MeSH
• progesteron farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• neurosteroidy * MeSH
• progesteron MeSH

Photocatalytic micromotors that exhibit wireless and controllable motion by light have been extensively explored for cancer treatment by photodynamic therapy (PDT). However, overexpressed glutathione (GSH) in the tumor microenvironment can down-regulate the reactive oxygen species (ROS) level for cancer therapy. Herein, we present dendrite-shaped light-powered hematite microrobots as an effective GSH depletion agent for PDT of prostate cancer cells. These hematite microrobots can display negative phototactic motion under light irradiation and flexible actuation in a defined path controlled by an external magnetic field. Non-contact transportation of micro-sized cells can be achieved by manipulating the microrobot's motion. In addition, the biocompatible microrobots induce GSH depletion and greatly enhance PDT performance. The proposed dendrite-shaped hematite microrobots contribute to developing dual light/magnetic field-powered micromachines for the biomedical field.

• Klíčová slova
• Cargo Transportation, Micromachines, Micromotors, Photocatalysis, Tumor Cells,
• MeSH
• dendrity MeSH
• fotochemoterapie * MeSH
• glutathion MeSH
• lidé MeSH
• magnetické pole MeSH
• nádorové mikroprostředí MeSH
• nádory prostaty * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ferric oxide MeSH Prohlížeč
• glutathion MeSH

All components of the CNS are surrounded by a diffuse extracellular matrix (ECM) containing chondroitin sulphate proteoglycans (CSPGs), heparan sulphate proteoglycans (HSPGs), hyaluronan, various glycoproteins including tenascins and thrombospondin, and many other molecules that are secreted into the ECM and bind to ECM components. In addition, some neurons, particularly inhibitory GABAergic parvalbumin-positive (PV) interneurons, are surrounded by a more condensed cartilage-like ECM called perineuronal nets (PNNs). PNNs surround the soma and proximal dendrites as net-like structures that surround the synapses. Attention has focused on the role of PNNs in the control of plasticity, but it is now clear that PNNs also play an important part in the modulation of memory. In this review we summarize the role of the ECM, particularly the PNNs, in the control of various types of memory and their participation in memory pathology. PNNs are now being considered as a target for the treatment of impaired memory. There are many potential treatment targets in PNNs, mainly through modulation of the sulphation, binding, and production of the various CSPGs that they contain or through digestion of their sulphated glycosaminoglycans.

• MeSH
• chondroitinsulfát proteoglykany * metabolismus   MeSH
• dendrity metabolismus   MeSH
• extracelulární matrix * metabolismus   MeSH
• neurony metabolismus   MeSH
• neuroplasticita fyziologie   MeSH
• synapse metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• chondroitinsulfát proteoglykany * MeSH

Ever since its first use in surgery, general anesthesia has been regarded as a medical miracle enabling countless life-saving diagnostic and therapeutic interventions without pain sensation and traumatic memories. Despite several decades of research, there is a lack of understanding of how general anesthetics induce a reversible coma-like state. Emerging evidence suggests that even brief exposure to general anesthesia may have a lasting impact on mature and especially developing brains. Commonly used anesthetics have been shown to destabilize dendritic spines and induce an enhanced plasticity state, with effects on cognition, motor functions, mood, and social behavior. Herein, we review the effects of the most widely used general anesthetics on dendritic spine dynamics and discuss functional and molecular correlates with action mechanisms. We consider the impact of neurodevelopment, anatomical location of neurons, and their neurochemical profile on neuroplasticity induction, and review the putative signaling pathways. It emerges that in addition to possible adverse effects, the stimulation of synaptic remodeling with the formation of new connections by general anesthetics may present tremendous opportunities for translational research and neurorehabilitation.

• Klíčová slova
• Actin cytoskeleton, Cofilin, Dendritic spine dynamics, Depression, General anesthesia, Neuroplasticity,
• MeSH
• anestetika celková * škodlivé účinky   MeSH
• celková anestezie škodlivé účinky   MeSH
• dendritické trny * MeSH
• mikrofilamenta MeSH
• neuroplasticita MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• anestetika celková * MeSH

BACKGROUND: Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes. METHODS: In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified. RESULTS: Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes. CONCLUSIONS: An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.

• Klíčová slova
• Chronic inflammatory demyelinating neuropathy, Diabetes mellitus, corneal confocal microscopy,
• MeSH
• chronická zánětlivá demyelinizační polyneuropatie diagnóza   epidemiologie   MeSH
• dendrity patologie   MeSH
• diabetes mellitus 2. typu diagnóza   epidemiologie   MeSH
• diabetické neuropatie diagnóza   epidemiologie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• konfokální mikroskopie metody   normy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervová vlákna patologie   MeSH
• rohovka patologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.

• Klíčová slova
• axon growth, axon regeneration, inter-organelle membrane contact sites, organelles,
• MeSH
• lidé MeSH
• organely metabolismus   patologie   MeSH
• poranění míchy * metabolismus   patologie   terapie   MeSH
• regenerace nervu * MeSH
• růstové kužele metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

G-protein coupled receptors (GPCRs) exist in an equilibrium of multiple conformational states, including different active states, which depend on the nature of the bound ligand. In consequence, different conformational states can initiate specific signal transduction pathways. The study identified compound 7e, which acts as a potent 5-hydroxytryptamine type 6 receptor (5-HT6R) neutral antagonist at Gs and does not impact neurite growth (process controlled by Cdk5). MD simulations highlighted receptor conformational changes for 7e and inverse agonist PZ-1444. In cell-based assays, neutral antagonists of the 5-HT6R (7e and CPPQ), but not inverse agonists (SB-258585, intepirdine, PZ-1444), displayed glioprotective properties against 6-hydroxydopamine-induced and doxorubicin-induced cytotoxicity. These suggest that targeting the activated conformational state of the 5-HT6R with neutral antagonists implicates the protecting properties of astrocytes. Additionally, 7e prevented scopolamine-induced learning deficits in the novel object recognition test in rats. We propose 7e as a probe for further understanding of the functional outcomes of different states of the 5-HT6R.

• MeSH
• agonisté serotoninových receptorů farmakologie   MeSH
• antagonisté serotoninu chemická syntéza   farmakologie   MeSH
• astrocyty účinky léků   MeSH
• imidazoly chemická syntéza   farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• molekulární konformace MeSH
• neurity účinky léků   MeSH
• neuroglie účinky léků   MeSH
• neuroprotektivní látky chemická syntéza   farmakologie   MeSH
• poruchy učení chemicky indukované   prevence a kontrola   MeSH
• potkani Sprague-Dawley MeSH
• pyridiny chemická syntéza   farmakologie   MeSH
• receptory serotoninové účinky léků   MeSH
• receptory spřažené s G-proteiny účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté serotoninových receptorů MeSH
• antagonisté serotoninu MeSH
• imidazoly MeSH
• imidazopyridine MeSH Prohlížeč
• neuroprotektivní látky MeSH
• pyridiny MeSH
• receptory serotoninové MeSH
• receptory spřažené s G-proteiny MeSH
• serotonin 6 receptor MeSH Prohlížeč