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  1. Article ; Online: Corrigendum to 'Role of serotonin 4 receptor in the growth of hippocampal neurons during the embryonic development in mice'.

    Agrawal, Lokesh / Vimal, Sunil Kumar / Shiga, Takashi

    Neuropharmacology

    2020  Volume 165, Page(s) 107916

    Language English
    Publishing date 2020-01-10
    Publishing country England
    Document type Published Erratum
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2019.107916
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Biodegradable and Electrically Conductive Melanin-Poly (3-Hydroxybutyrate) 3D Fibrous Scaffolds for Neural Tissue Engineering Applications.

    Agrawal, Lokesh / Vimal, Sunil Kumar / Barzaghi, Paolo / Shiga, Takashi / Terenzio, Marco

    Macromolecular bioscience

    2022  , Page(s) e2200315

    Abstract: Due to the severity of peripheral nerve injuries (PNI) and spinal cord injuries (SCI), treatment options for patients are limited. In this context, biomaterials designed to promote regeneration and reinstate the lost function are being explored. Such ... ...

    Abstract Due to the severity of peripheral nerve injuries (PNI) and spinal cord injuries (SCI), treatment options for patients are limited. In this context, biomaterials designed to promote regeneration and reinstate the lost function are being explored. Such biomaterials should be able to mimic the biological, chemical, and physical cues of the extracellular matrix for maximum effectiveness as therapeutic agents. Development of biomaterials with desirable physical, chemical, and electrical properties, however, has proven challenging. Here a novel biomaterial formulation achieved by blending the pigment melanin and the natural polymer Poly-3-hydroxybutyrate (PHB) is proposed. Physio-chemical measurements of electrospun fibers reveal a feature rich surface nano-topography, a semiconducting-nature, and brain-tissue-like poroviscoelastic properties. Resulting fibers improve cell adhesion and growth of mouse sensory and motor neurons, without any observable toxicity. Further, the presence of polar functional groups positively affect the kinetics of fibers degradation at a pH (≈7.4) comparable to that of body fluids. Thus, melanin-PHB blended scaffolds are found to be physio-chemically, electrically, and biologically compatible with neural tissues and could be used as a regenerative modality for neural tissue injuries. A biomaterial for scaffolds intended to promote regeneration of nerve tissue after injury is developed. This biomaterial, obtained by mixing the pigment melanin and the natural polymer PHB, is biodegradable, electrically conductive, and beneficial to the growth of motor and sensory neurons. Thus, it is believed that this biomaterial can be used in the context of healthcare applications.
    Language English
    Publishing date 2022-09-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2039130-4
    ISSN 1616-5195 ; 1616-5187
    ISSN (online) 1616-5195
    ISSN 1616-5187
    DOI 10.1002/mabi.202200315
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Role of serotonin 4 receptor in the growth of hippocampal neurons during the embryonic development in mice.

    Agrawal, Lokesh / Vimal, Sunil Kumar / Shiga, Takashi

    Neuropharmacology

    2019  Volume 158, Page(s) 107712

    Abstract: Serotonin (5-HT) homeostasis is critical for the brain development which influences neurogenesis, neuronal migration, and circuit formation. Distinctive distribution patterns of serotonin receptors (5-HTRs) in the brain govern various physiological ... ...

    Abstract Serotonin (5-HT) homeostasis is critical for the brain development which influences neurogenesis, neuronal migration, and circuit formation. Distinctive distribution patterns of serotonin receptors (5-HTRs) in the brain govern various physiological activities. Amongst the 5-HTRs, serotonin 4 receptor (5-HT4R) is widely expressed in embryonic forebrain and affects neuronal development, synaptogenesis, and behavior, but its specific role in brain development is still not completely understood. Therefore, in the present study, we addressed the roles of 5-HT4R in the growth of hippocampal neurons during the development of mice brain. We cultured hippocampal neurons of the mouse at embryonic day 18 and then treatment of 5-HT4R agonist RS67333 was employed. We found RS67333 significantly increased the axonal length, diameter and branching along with total dendritic length, number of primary dendrites and their branching. In addition, these effects were neutralized by the concomitant treatment of 5-HT4R antagonist GR125487, which confirmed the specific role of the 5-HT4R in the growth of axon and dendrites. Further, the treatment of RS67333 upregulated the mRNA expression of collapsin response mediator protein-2 (CRMP2) and non-phosphorylated CRMP2 (npCRMP2) together with neurotrophic factors (BDNF, NT-3, NGF) and TRK-A. Additionally, the current research findings reveal that the knockdown of CRMP2 inhibited RS67333-induced growth of the axons and dendrites, which indicates that CRMP2 is required for the 5-HT4R-mediated growth of the axons and dendrites. Overall, the findings of the present in vitro study enrich the understanding and provide insight roles of 5-HT4R in embryonic brain development by promoting the growth of hippocampal neurons.
    MeSH term(s) Aniline Compounds/pharmacology ; Animals ; Axons/drug effects ; Brain-Derived Neurotrophic Factor/drug effects ; Brain-Derived Neurotrophic Factor/genetics ; Dendrites/drug effects ; Embryo, Mammalian ; Gene Knockdown Techniques ; Hippocampus/cytology ; Hippocampus/drug effects ; Hippocampus/embryology ; Indoles/pharmacology ; Intercellular Signaling Peptides and Proteins/genetics ; Mice ; Nerve Growth Factor/drug effects ; Nerve Growth Factor/genetics ; Nerve Growth Factors/drug effects ; Nerve Growth Factors/genetics ; Nerve Tissue Proteins/drug effects ; Nerve Tissue Proteins/genetics ; Neurogenesis/drug effects ; Neurogenesis/physiology ; Neurons/drug effects ; Neurons/metabolism ; Piperidines/pharmacology ; RNA, Messenger/drug effects ; RNA, Messenger/genetics ; Receptors, Serotonin, 5-HT4/metabolism ; Serotonin 5-HT4 Receptor Agonists/pharmacology ; Serotonin 5-HT4 Receptor Antagonists/pharmacology ; Sulfonamides/pharmacology
    Chemical Substances Aniline Compounds ; Bdnf protein, mouse ; Brain-Derived Neurotrophic Factor ; Indoles ; Intercellular Signaling Peptides and Proteins ; Nerve Growth Factors ; Nerve Tissue Proteins ; Piperidines ; RNA, Messenger ; Serotonin 5-HT4 Receptor Agonists ; Serotonin 5-HT4 Receptor Antagonists ; Sulfonamides ; collapsin response mediator protein-2 ; neurotropin 3, mouse ; Receptors, Serotonin, 5-HT4 (158165-40-3) ; RS 67333 (160845-95-4) ; Nerve Growth Factor (9061-61-4) ; GR 113808 (ZT350OYT3I)
    Language English
    Publishing date 2019-07-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2019.107712
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Neurodegenerative Disorders of Alzheimer, Parkinsonism, Amyotrophic Lateral Sclerosis and Multiple Sclerosis: An Early Diagnostic Approach for Precision Treatment.

    Pathak, Nishit / Vimal, Sunil Kumar / Tandon, Ishi / Agrawal, Lokesh / Hongyi, Cao / Bhattacharyya, Sanjib

    Metabolic brain disease

    2021  Volume 37, Issue 1, Page(s) 67–104

    Abstract: Neurodegenerative diseases (NDs) are characterised by progressive dysfunction of synapses, neurons, glial cells and their networks. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or ... ...

    Abstract Neurodegenerative diseases (NDs) are characterised by progressive dysfunction of synapses, neurons, glial cells and their networks. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormalities. The most common neurodegenerative disorders are amyloidosis, tauopathies, a-synucleinopathy, and TAR DNA-binding protein 43 (TDP-43) proteopathy. The protein abnormalities in these disorders have abnormal conformational properties along with altered cellular mechanisms, and they exhibit motor deficit, mitochondrial malfunction, dysfunctions in autophagic-lysosomal pathways, synaptic toxicity, and more emerging mechanisms such as the roles of stress granule pathways and liquid-phase transitions. Finally, for each ND, microglial cells have been reported to be implicated in neurodegeneration, in particular, because the microglial responses can shift from neuroprotective to a deleterious role. Growing experimental evidence suggests that abnormal protein conformers act as seed material for oligomerization, spreading from cell to cell through anatomically connected neuronal pathways, which may in part explain the specific anatomical patterns observed in brain autopsy sample. In this review, we mention the human pathology of select neurodegenerative disorders, focusing on how neurodegenerative disorders (i.e., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis) represent a great healthcare problem worldwide and are becoming prevalent because of the increasing aged population. Despite many studies have focused on their etiopathology, the exact cause of these diseases is still largely unknown and until now with the only available option of symptomatic treatments. In this review, we aim to report the systematic and clinically correlated potential biomarker candidates. Although future studies are necessary for their use in early detection and progression in humans affected by NDs, the promising results obtained by several groups leads us to this idea that biomarkers could be used to design a potential therapeutic approach and preclinical clinical trials for the treatments of NDs.
    MeSH term(s) Aged ; Alzheimer Disease/diagnosis ; Amyotrophic Lateral Sclerosis/diagnosis ; Amyotrophic Lateral Sclerosis/pathology ; Humans ; Multiple Sclerosis ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/drug therapy ; Parkinson Disease
    Language English
    Publishing date 2021-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 632824-6
    ISSN 1573-7365 ; 0885-7490
    ISSN (online) 1573-7365
    ISSN 0885-7490
    DOI 10.1007/s11011-021-00800-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Therapeutic potential of serotonin 4 receptor for chronic depression and its associated comorbidity in the gut.

    Agrawal, Lokesh / Korkutata, Mustafa / Vimal, Sunil Kumar / Yadav, Manoj Kumar / Bhattacharyya, Sanjib / Shiga, Takashi

    Neuropharmacology

    2020  Volume 166, Page(s) 107969

    Abstract: The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50-60% have been reported to have progression of gut diseases. In the last two decades, ...

    Abstract The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50-60% have been reported to have progression of gut diseases. In the last two decades, researchers introduced incipient physiological roles for serotonin (5-HT) receptors (5-HTRs), suggesting their importance as a potential pharmacological target in various psychiatric and gut diseases. A growing body of evidence suggests that 5-HT systems affect the brain-gut axis in depressive patients, which leads to gut comorbidity. Recently, preclinical trials of 5-HT4R agonists and antagonists were promising as antipsychotic and prokinetic agents. In the current review, we address the possible pharmacological role and contribution of 5-HT4R in the pathophysiology of chronic depression and associated gut abnormalities. Physiologically, during depression episodes, centers of the sympathetic and parasympathetic nervous system couple together with neuroendocrine systems to alter the function of hypothalamic-pituitary-adrenal (HPA) axis and enteric nervous system (ENS), which in turn leads to onset of gastrointestinal tract (GIT) disorders. Consecutively, the ENS governs a broad spectrum of physiological activities of gut, such as visceral pain and motility. During the stages of emotional stress, hyperactivity of the HPA axis alters the ENS response to physiological and noxious stimuli. Consecutively, stress-induced flare, swelling, hyperalgesia and altered reflexes in gut eventually lead to GIT disorders. In summary, the current review provides prospective information about the role and mechanism of 5-HT4R-based therapeutics for the treatment of depressive disorder and possible consequences for the gut via brain-gut axis interactions. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
    MeSH term(s) Animals ; Brain/drug effects ; Brain/metabolism ; Comorbidity ; Depression/drug therapy ; Depression/epidemiology ; Depression/metabolism ; Gastrointestinal Diseases/drug therapy ; Gastrointestinal Diseases/epidemiology ; Gastrointestinal Diseases/metabolism ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/physiology ; Humans ; Receptors, Serotonin, 5-HT4/metabolism ; Serotonin 5-HT4 Receptor Agonists/pharmacology ; Serotonin 5-HT4 Receptor Agonists/therapeutic use ; Serotonin 5-HT4 Receptor Antagonists/pharmacology ; Serotonin 5-HT4 Receptor Antagonists/therapeutic use
    Chemical Substances Serotonin 5-HT4 Receptor Agonists ; Serotonin 5-HT4 Receptor Antagonists ; Receptors, Serotonin, 5-HT4 (158165-40-3)
    Language English
    Publishing date 2020-01-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2020.107969
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Self-Therapeutic Nanoparticle That Alters Tau Protein and Ameliorates Tauopathy Toward a Functional Nanomedicine to Tackle Alzheimer's.

    Vimal, Sunil Kumar / Zuo, Hua / Wang, Zhengwu / Wang, Hongrun / Long, Zhiliang / Bhattacharyya, Sanjib

    Small (Weinheim an der Bergstrasse, Germany)

    2020  Volume 16, Issue 16, Page(s) e1906861

    Abstract: Tauopathy is a complex disorder associated at the junction of several other pathologies. Intrinsically disordered tau protein remains therapeutically challenging due to its undruggable nature and is a possible reason for monumental failure of several tau- ...

    Abstract Tauopathy is a complex disorder associated at the junction of several other pathologies. Intrinsically disordered tau protein remains therapeutically challenging due to its undruggable nature and is a possible reason for monumental failure of several tau-based therapies. Herein, nanogold remodeled tau is reported as a pseudo-nanochaperon and shows therapeutic benefit by passive targeting in transgenic tau P301L mutant mice. Treatment with nanogold polyethylene glycol (Au-PEG) conjugate moderately improves the learning ability of the tau P301L mice that corroborates with diminished phosphorylated tau burden. Circulating total tau level that acts in a prion fashion is significantly reduced upon Au-PEG treatment. Similarly, a high level of tau is found in macaque monkey serum and Au-PEG inhibits amyloidosis of Alzheimer's patients and primate's serum samples ex vivo. Addtionally, brain MRI of an old aged macaque monkey shows the decrease of grey matter, which correlates with mutual loss of grey matter upon progressive dementia as reported. Au-PEG tunes tau and other circulating pro-dementia factors that are present in human AD serum, by remodeling the protein and repairing aberrant proteostasis. Alteration of proteotoxic tau function by nanogold as a kinetic stablizer holds translational potential to combat socially challenging dementia.
    MeSH term(s) Alzheimer Disease/drug therapy ; Animals ; Brain/metabolism ; Disease Models, Animal ; Humans ; Macaca ; Mice ; Mice, Transgenic ; Nanomedicine ; Nanoparticles ; Tauopathies/drug therapy ; tau Proteins/metabolism
    Chemical Substances tau Proteins
    Language English
    Publishing date 2020-03-19
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.201906861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A simple method for fabrication of electrospun fibers with controlled degree of alignment having potential for nerve regeneration applications.

    Vimal, Sunil Kumar / Ahamad, Nadim / Katti, Dhirendra S

    Materials science & engineering. C, Materials for biological applications

    2016  Volume 63, Page(s) 616–627

    Abstract: In peripheral nerve injuries where direct suturing of nerve endings is not feasible, nerve regeneration has been facilitated through the use of artificially aligned fibrous scaffolds that provide directional growth of neurons to bridge the gap. The ... ...

    Abstract In peripheral nerve injuries where direct suturing of nerve endings is not feasible, nerve regeneration has been facilitated through the use of artificially aligned fibrous scaffolds that provide directional growth of neurons to bridge the gap. The degree of fiber alignment is crucial and can impact the directionality of cells in a fibrous scaffold. While there have been multiple approaches that have been used for controlling fiber alignment, however, they have been associated with a compromised control on other properties, such as diameter, morphology, curvature, and topology of fibers. Therefore, the present study demonstrates a modified electrospinning set-up, that enabled fabrication of electrospun fibers with controlled degree of alignment from non-aligned (NA), moderately aligned (MA, 75%) to highly aligned (HA, 95%) sub-micron fibers while keeping other physical properties unchanged. The results demonstrate that the aligned fibers (MA and HA) facilitated directional growth of human astrocytoma cells (U373), wherein the aspect ratio of cells was found to increase with an increase in degree of fibers alignment. In contrast to NA and MA fibers, the HA fibers showed improved contact guidance to U373 cells that was demonstrated by a significantly higher cell aspect ratio and nuclear aspect ratio. In conclusion, the present study demonstrated a modified electrospinning setup to fabricate differentially aligned fibrous scaffolds with the HA fibers showing potential for use in neural tissue engineering.
    MeSH term(s) Biocompatible Materials/chemistry ; Biocompatible Materials/pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; Humans ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Nerve Regeneration/drug effects ; Nerve Regeneration/physiology
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2016-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2012160-X
    ISSN 1873-0191 ; 0928-4931
    ISSN (online) 1873-0191
    ISSN 0928-4931
    DOI 10.1016/j.msec.2016.03.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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