Osteocalcin: A Protein Hormone Connecting Metabolism, Bone and Testis Function

2020 ◽  
Vol 27 (12) ◽  
pp. 1268-1275
Author(s):  
Luca De Toni ◽  
Kenda Jawich ◽  
Maurizio De Rocco Ponce ◽  
Andrea Di Nisio ◽  
Carlo Foresta
Keyword(s):  
Experimental Data ◽  
Male Fertility ◽  
Endocrine Function ◽  
Protective Effects ◽  
Original Function ◽  
Endocrine Organ ◽  
The Central Nervous System ◽  
Depressive States ◽  
Novel Therapeutic

During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic functions. Since that time, the role of OCN as osteokine has been more and more widened appreciated and detailed by the major use of animal models, starting from the original function in the bone extracellular matrix as Gla-protein and spanning from the protective effects towards weight gain, insulin sensitivity and glucose homeostasis, to the anabolic and metabolic roles in skeletal muscle, to the stimulating effects on the testis endocrine function and male fertility, to the most recent preservation from anxious and depressive states through a direct activity on the central nervous system. In this review, experimental data supporting the inter-organ communication roles of this protein are discussed, together with the available data supporting the consistency between experimental data obtained in animals and those reported in humans. In addition, a specific session has been devoted to the possible significance the OCN as a template agonist on its receptor GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states and male infertility.

scholarly journals Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia

2020 ◽  
Vol 21 (22) ◽  
pp. 8630
Author(s):  
Filippo Sean Giorgi ◽  
Francesca Biagioni ◽  
Alessandro Galgani ◽  
Nicola Pavese ◽  
Gloria Lazzeri ◽  
...  
Keyword(s):  
Experimental Data ◽  
Locus Coeruleus ◽  
Clinical Symptoms ◽  
Experimental Studies ◽  
Anatomy And Physiology ◽  
The Central Nervous System ◽  
Near Future

Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer’s disease (AD) and in Parkinson’s disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. Several experimental studies have shown that noradrenaline modulates neuroinflammation, mainly by acting on microglia/astrocytes function. In the present review, after a brief introduction on the anatomy and physiology of LC, we provide an overview of experimental data supporting a pathogenetic role of LC degeneration in AD and PD. Then, we describe in detail experimental data, obtained in vitro and in vivo in animal models, which support a potential role of neuroinflammation in such a link, and the specific molecules (i.e., released cytokines, glial receptors, including pattern recognition receptors and others) whose expression is altered by LC degeneration and might play a key role in AD/PD pathogenesis. New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients.

scholarly journals Role of the Gut Microbiota in Ischemic Stroke

2017 ◽  
Vol 01 (04) ◽  
pp. E287-E293 ◽  
Author(s):  
Katarzyna Winek ◽  
Ulrich Dirnagl ◽  
Andreas Meisel
Keyword(s):  
Risk Factors ◽  
Experimental Data ◽  
Central Nervous System ◽  
Gut Microbiota ◽  
Stroke Risk ◽  
Stroke Outcome ◽  
Stroke Risk Factors ◽  
The Central Nervous System ◽  
Peripheral Immune Response

AbstractRecent studies have provided evidence for the role of the gut microbiota in the homeostasis of the central nervous system (CNS) and in the pathophysiology of its disorders, e. g. by regulation of the peripheral immune response. In this article, we discuss the importance of the gut microbiota in stroke by providing a summary of available clinical and experimental data suggesting that 1) stroke changes the gut microbiome, 2) microbiota modulates stroke outcome and 3) microbiota plays an important role in the pathogenesis of stroke (risk factors). Currently available clinical and experimental evidence suggests an important role of gut microbiota in stroke and promises clinically relevant discoveries within coming years.

S100B raises the alert in subarachnoid hemorrhage

2016 ◽  
Vol 27 (7) ◽  
pp. 745-759 ◽  
Author(s):  
Zhao Zhong Chong
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Calcium Binding ◽  
Intracellular Signaling ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Protein S100b ◽  
Novel Therapeutic

AbstractSubarachnoid hemorrhage (SAH) is a devastating disease with high mortality and mobility, the novel therapeutic strategies of which are essentially required. The calcium binding protein S100B has emerged as a brain injury biomarker that is implicated in pathogenic process of SAH. S100B is mainly expressed in astrocytes of the central nervous system and functions through initiating intracellular signaling or via interacting with cell surface receptor, such as the receptor of advanced glycation end products. The biological roles of S100B in neurons have been closely associated with its concentrations, resulting in either neuroprotection or neurotoxicity. The levels of S100B in the blood have been suggested as a biomarker to predict the progress or the prognosis of SAH. The role of S100B in the development of cerebral vasospasm and brain damage may result from the induction of oxidative stress and neuroinflammation after SAH. To get further insight into mechanisms underlying the role of S100B in SAH based on this review might help us to find novel therapeutic targets for SAH.

scholarly journals Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities

2021 ◽  
Vol 22 (11) ◽  
pp. 6126
Author(s):  
Magdalena Groblewska ◽  
Barbara Mroczko
Keyword(s):  
Normal Development ◽  
Malignant Tumors ◽  
Antiangiogenic Therapy ◽  
Primary Tumors ◽  
Pubmed Database ◽  
Multistep Process ◽  
The Central Nervous System ◽  
Antiangiogenic Factors ◽  
Novel Therapeutic

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.

scholarly journals The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief

2011 ◽  
Vol 2011 ◽  
pp. 1-19 ◽  
Author(s):  
Jenny L. Wilkerson ◽  
Erin D. Milligan
Keyword(s):  
Pain Relief ◽  
Cannabinoid Receptor ◽  
Receptor Subtype ◽  
Pain Processing ◽  
Neuronal Mechanisms ◽  
Cannabinoid Compounds ◽  
The Central Nervous System ◽  
Pathological Pain ◽  
Novel Therapeutic

Under normal conditions, acute pain processing consists of well-characterized neuronal signaling events. When dysfunctional pain signaling occurs, pathological pain ensues. Glial activation and their released factors participate in the mediation of pathological pain. The use of cannabinoid compounds for pain relief is currently an area of great interest for both basic scientists and physicians. These compounds, bind mainly either the cannabinoid receptor subtype 1 (CB1R) or cannabinoid receptor subtype 2 (CB2R) and are able to modulate pain. Although cannabinoids were initially only thought to modulate pain via neuronal mechanisms within the central nervous system, strong evidence now supports that CB2R cannabinoid compounds are capable of modulating glia, (e.g. astrocytes and microglia) for pain relief. However, the mechanisms underlying cannabinoid receptor-mediated pain relief remain largely unknown. An emerging body of evidence supports that CB2R agonist compounds may prove to be powerful novel therapeutic candidates for the treatment of chronic pain.

scholarly journals The Emerging Role of Microglia in Neuromyelitis Optica

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingjun Chen ◽  
Dale B. Bosco ◽  
Yanlu Ying ◽  
Dai-Shi Tian ◽  
Long-Jun Wu
Keyword(s):  
Animal Models ◽  
Neuromyelitis Optica ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Therapeutic Approaches ◽  
The Central Nervous System ◽  
Water Channel Protein ◽  
Novel Therapeutic

Neuromyelitis optica (NMO) is an autoantibody-triggered neuro-inflammatory disease which preferentially attacks the spinal cord and optic nerve. Its defining autoantibody is specific for the water channel protein, aquaporin‐4 (AQP4), which primarily is localized at the end-feet of astrocytes. Histopathology studies of early NMO lesions demonstrated prominent activation of microglia, the resident immune sentinels of the central nervous system (CNS). Significant microglial reactivity is also observed in NMO animal models induced by introducing AQP4-IgG into the CNS. Here we review the potential roles for microglial activation in human NMO patients as well as different animal models of NMO. We will focus primarily on the molecular mechanisms underlying microglial function and microglia-astrocyte interaction in NMO pathogenesis. Understanding the role of microglia in NMO pathology may yield novel therapeutic approaches for this disease.

NeuN As a Neuronal Nuclear Antigen and Neuron Differentiation Marker

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 42-47 ◽  
Author(s):  
V. V. Gusel’nikova ◽  
D. E. Korzhevskiy
Keyword(s):  
Experimental Data ◽  
Intracellular Localization ◽  
Nuclear Antigen ◽  
Structure And Properties ◽  
Immunocytochemical Detection ◽  
Perinuclear Cytoplasm ◽  
Diagnosis Of Cancer ◽  
Morphological Diagnosis ◽  
The Central Nervous System ◽  
Differentiation Marker

The NeuN protein is localized in nuclei and perinuclear cytoplasm of most of the neurons in the central nervous system of mammals. Monoclonal antibodies to the NeuN protein have been actively used in the immunohistochemical research of neuronal differentiation to assess the functional state of neurons in norm and pathology for more than 20 years. Recently, NeuN antibodies have begun to be applied in the differential morphological diagnosis of cancer. However, the structure of the protein, which can be revealed by antibodies to NeuN, remained unknown until recently, and the functions of the protein are still not fully clear. In the present mini-review, data on NeuN accumulated so far are summarized and analyzed. Data on the structure and properties of the protein, its isoforms, intracellular localization, and hypothesized functions are reported. The application field of immunocytochemical detection of NeuN in scientific and clinical studies, as well as the difficulties in the interpretation of the obtained experimental data and their possible causes, is described in details.

METABOLIC AND ENDOCRINE ASPECTS OF THE WHIRLER MUTATION IN MALE MICE

1970 ◽  
Vol 64 (2) ◽  
pp. 347-358
Author(s):  
A. Stanley Weltman ◽  
Arthur M. Sackler
Keyword(s):  
Locomotor Activity ◽  
Endocrine Function ◽  
Metabolic Rates ◽  
Heterozygous Female ◽  
Endocrine Organ ◽  
General Body ◽  
Adrenocortical Activity ◽  
Body Weights ◽  
Seminal Vesicle Weight ◽  
Eosinophil Counts

ABSTRACT Body weight, metabolic rate, locomotor activity and alterations in endocrine organ activity were noted in recessive homozygous male whirler mice and the phenotypically »normal« heterozygotes. Representative populations of the two types were studied at different age levels. In general, body weights of the whirler mice were consistently and significantly lower. Open-field locomotion studies similarly indicated heightened locomotor activity. Total leukocyte and eosinophil counts were either markedly or significantly lower in the homozygous vs. heterozygous whirler groups. Evaluation of relative organ weights showed significantly increased adrenal weights in whirler mice sacrificed at 14 weeks and 11 months of age. These changes were accompanied by involution of the thymus. Thus, the varied data indicate persistent increased metabolism and adrenocortical activity during the life-span of the whirler mice. Seminal vesicle weight decreases in the whirler males at 11 months suggest lower gonadal function. The findings are in accord with previous studies of alterations in metabolic rates and endocrine function of homozygous whirler vs. heterozygous female mice.

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