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Acta Neuropathologica Communications Jun 2024We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we...
We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer's disease (AD, n = 8), Pick's disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.
Topics: Humans; White Matter; Male; Schizophrenia; Female; Cerebral Cortex; Aged; Middle Aged; Neurodegenerative Diseases; Aged, 80 and over; Oligopeptides; Adult; Neurons
PubMed: 38943180
DOI: 10.1186/s40478-024-01792-1 -
Marine Drugs May 2024Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on...
Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on the modulation of the inflammatory response mainly by microglia/macrophages. The extracts and metabolites of marine sponges have been presented as anti-inflammatory. This study evaluated the toxicity of an extract and purified compound from the Brazilian marine sponge as well as its neuroprotection against inflammatory damage associated with the modulation of microglia response. PC12 neuronal cells and neonatal rat microglia were treated with the methanolic extract of (AF-MeOH, 0.1-200 μg/mL) or with its purified dimethyl ketal of 3,5-dibromoverongiaquinol (AF-H1, 0.1-100 μM). Cytotoxicity was determined by MTT tetrazolium, Trypan blue, and propidium iodide; microglia were also treated with the conditioned medium (CM) from PC12 cells in different conditions. The microglia phenotype was determined by the expression of Iba-1 and CD68. AF-MeOH and AF-H1 were not toxic to PC12 or the microglia. Inflammatory damage with lipopolysaccharide (LPS, 5 μg/mL) was not observed in the PC12 cells treated with AF-MeOH (1-10 μg/mL) or AF-H1 (1-10 μM). Microglia subjected to the CM from PC12 cells treated with LPS and AF-MeOH or AF-H1 showed the control phenotype-like (multipolar, low-CD68), highlighting the anti-neuroinflammatory and neuroprotective effect of components of this marine sponge.
Topics: Animals; Microglia; Rats; Porifera; Neuroprotective Agents; PC12 Cells; Brazil; Anti-Inflammatory Agents; Hydrocarbons, Brominated; Inflammation
PubMed: 38921546
DOI: 10.3390/md22060235 -
EMBO Reports Jun 2024The mammalian neocortex is formed by sequential radial migration of newborn excitatory neurons. Migrating neurons undergo a multipolar-to-bipolar transition at the...
The mammalian neocortex is formed by sequential radial migration of newborn excitatory neurons. Migrating neurons undergo a multipolar-to-bipolar transition at the subplate (SP) layer, where extracellular matrix (ECM) components are abundantly expressed. Here, we investigate the role of the ECM at the SP layer. We show that TGF-β signaling-related ECM proteins, and their downstream effector, p-smad2/3, are selectively expressed in the SP layer. We also find that migrating neurons express a disintegrin and metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. Knockdown and knockout of Adamts2 suppresses the multipolar-to-bipolar transition of migrating neurons and disturbs radial migration. Time-lapse luminescence imaging of TGF-β signaling indicates that ADAMTS2 activates this signaling pathway in migrating neurons during the multipolar-to-bipolar transition at the SP layer. Overexpression of TGF-β2 in migrating neurons partially rescues migration defects in ADAMTS2 knockout mice. Our data suggest that ADAMTS2 secreted by the migrating multipolar neurons activates TGF-β signaling by ECM remodeling of the SP layer, which might drive the multipolar to bipolar transition.
PubMed: 38871984
DOI: 10.1038/s44319-024-00174-x -
Folia Histochemica Et Cytobiologica 2024Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal...
INTRODUCTION
Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal Mongolian gerbil is a member of the rodent family Muridae that exhibits unique physiological, anatomical, and behavioral differences from the nocturnal rat and mouse, which render it a useful model for studying the visual system. The purpose of this study was to confirm the distribution and morphology of neurons that contain nitric oxide synthase (NOS) and their pattern of co-expressing NOS with neuropeptide Y (NPY), somatostatin (SST), and gamma-aminobutyric acid (GABA) in the visual cortex of Mongolian gerbils.
MATERIALS AND METHODS
Mongolian gerbils were used in the study. We confirmed the localization of NOS in the visual cortex of Mongolian gerbils using horseradish peroxidase immunocytochemistry, fluorescent immunocytochemistry, and conventional confocal microscopy.
RESULTS
NOS-immunoreactive (IR) neurons were present in all layers of the visual cortex of the Mongolian gerbil, with the exception of layer I, with the highest density observed in layer V (50.00%). The predominant type of NOS-IR neurons was multipolar round/oval cells (60.96%). Two-color immunofluorescence revealed that 100% NOS-IR neurons were co-labeled with NPY and SST and 34.55% were co-labeled with GABA.
CONCLUSIONS
Our findings of the laminar distribution and morphological characteristics of NOS-IR neurons, as well as the colocalization patterns of NOS-IR neurons with NPY, SST, and GABA, indicated the presence of species-specific differences, suggesting the functional diversity of NO in the visual cortex. This study provides valuable data on the anatomical organization of NOS-IR neurons and, consequently, a better understanding of the functional aspects of NO and species diversity.
Topics: Rats; Mice; Animals; Gerbillinae; Neurons; Nitric Oxide Synthase; Visual Cortex; gamma-Aminobutyric Acid
PubMed: 38563048
DOI: 10.5603/fhc.99227 -
ELife Mar 2024Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in...
Radial neuronal migration is a key neurodevelopmental event for proper cortical laminar organization. The multipolar-to-bipolar transition, a critical step in establishing neuronal polarity during radial migration, occurs in the subplate/intermediate zone (SP/IZ), a distinct region of the embryonic cerebral cortex. It has been known that the extracellular matrix (ECM) molecules are enriched in the SP/IZ. However, the molecular constitution and functions of the ECM formed in this region remain poorly understood. Here, we identified neurocan (NCAN) as a major chondroitin sulfate proteoglycan in the mouse SP/IZ. NCAN binds to both radial glial-cell-derived tenascin-C (TNC) and hyaluronan (HA), a large linear polysaccharide, forming a ternary complex of NCAN, TNC, and HA in the SP/IZ. Developing cortical neurons make contact with the ternary complex during migration. The enzymatic or genetic disruption of the ternary complex impairs radial migration by suppressing the multipolar-to-bipolar transition. Furthermore, both TNC and NCAN promoted the morphological maturation of cortical neurons in vitro. The present results provide evidence for the cooperative role of neuron- and radial glial-cell-derived ECM molecules in cortical development.
Topics: Animals; Mice; Neurons; Extracellular Matrix; Cerebral Cortex; Cell Movement; Chondroitin Sulfate Proteoglycans
PubMed: 38512724
DOI: 10.7554/eLife.92342 -
The Korean Journal of Physiology &... Mar 2024The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic...
The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate- induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.
PubMed: 38414399
DOI: 10.4196/kjpp.2024.28.2.165 -
IScience Mar 2024The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal...
The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) and regulate circadian rhythms in behavior and physiology. SCN neurons acquire functional and morphological specializations from waves of transcription factors (TFs) that are expressed during neurogenesis. However, the generation of SCN neurons has never been achieved. Here we supplemented a highly efficient neuronal conversion protocol with TFs that are expressed during SCN neurogenesis, namely , , , and . Neurons induced from mouse and human fibroblasts predominantly exhibited neuronal properties such as bipolar or multipolar morphologies, GABAergic neurons with expression of VIP. Our study reveals a critical contribution of these TFs to the development of vasoactive intestinal peptide (Vip) expressing neurons in the SCN, suggesting the regenerative potential of neuronal subtypes contained in the SCN for future SCN regeneration and disease remodeling.
PubMed: 38384840
DOI: 10.1016/j.isci.2024.109051 -
Neuroscience Bulletin Nov 2023Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in...
Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.
Topics: Animals; Humans; Mice; Actin Cytoskeleton; Actins; Epilepsy; Neurons; Receptors, CXCR5; Seizures
PubMed: 37460877
DOI: 10.1007/s12264-023-01087-w -
Clinical Neurophysiology : Official... Aug 2023Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their...
OBJECTIVE
Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials.
METHODS
The median nerves of both upper arms of five healthy individuals were investigated. The propagating magnetic field of the action potential was recorded using magnetoneurography, reconstructed into a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes.
RESULTS
Reconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conductor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approximately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones.
CONCLUSIONS
Magnetoneurography allows the visualization and quantitative evaluation of action currents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings.
SIGNIFICANCE
Magnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.
Topics: Humans; Action Potentials; Median Nerve; Axons; Evoked Potentials; Magnetic Fields; Electric Stimulation
PubMed: 37307628
DOI: 10.1016/j.clinph.2023.05.006