scholarly journals CNS-Selective Estrogen Therapy

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 31
Author(s):  
Katalin Prokai-Tatrai ◽  
Laszlo Prokai
Keyword(s):  
Psychiatric Symptoms ◽  
Estrogen Therapy ◽  
The Body ◽  
Therapeutic Interventions ◽  
Eye Health ◽  
The Central Nervous System ◽  
17Β Estradiol ◽  
Hormonal Exposure ◽  
Bioanalytical Assays ◽  
The Brain

17β-Estradiol (E2), the main human estrogen, has been known to exert multiple actions throughout the body, including in the central nervous system (CNS). In particular, it has been shown that E2 is gender-independently needed for brain and eye health. Lack of E2 due to normal aging and/or pathological processes leads to neurological and psychiatric diseases as well as accelerated neurodegeneration. Current estrogen replacement therapies, however, cannot be used as therapeutic interventions to treat these maladies due to a profound, unwanted hormonal exposure to the rest of the body. In this presentation, we show that the small-molecule bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) produces E2 only in the CNS but remains inert in the rest of the body, both upon chronic systemic and topical administrations, thereby avoiding the detrimental side-effects of the hormone, such as stimulation of the uterus and tumor growth. The highly localized production of E2 in the CNS will be shown through a series of bioanalytical assays and efficacy studies using animal models of estrogen-responsive maladies pertaining to the brain and the retina. Owing to DHED’s significantly more favorable physicochemical properties than the highly lipophilic parent E2 for transport through biological membranes such as the blood-brain barrier or the cornea, a highly effective E2 therapy can be achieved in rodents upon prodrug administration, which further enhances therapeutic safety. Altogether, our patented DHED approach shows unprecedented selectivity to deliver E2 into the CNS and, thus, promises a high translation value in terms of efficacious and safe treatment against neurodegeneration as well as neurological and psychiatric symptoms arising from estrogen deficiency.

scholarly journals Modern aspects of neuropathogenesis and neurological manifestations of COVID-19

2021 ◽  
Vol 17 (2) ◽  
pp. 6-15
Author(s):  
L.A. Dziak ◽  
O.S. Tsurkalenko ◽  
K.V. Chekha ◽  
V.M. Suk
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
The Body ◽  
Altered Level ◽  
Wide Range ◽  
The Central Nervous System ◽  
The Brain

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.

scholarly journals Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

2021 ◽  
Vol 22 (13) ◽  
pp. 6858
Author(s):  
Fanny Gaudel ◽  
Gaëlle Guiraudie-Capraz ◽  
François Féron
Keyword(s):  
G Proteins ◽  
The Body ◽  
Trace Amines ◽  
Chemical Senses ◽  
Brain Areas ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Human Brains ◽  
The Brain ◽  
Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

Nerves as a Problem

2013 ◽  
Author(s):  
Edward Shorter
Keyword(s):  
Psychiatric Symptoms ◽  
The Body ◽  
Physical Sign ◽  
Wall Street ◽  
The Wall Street Journal ◽  
Michael Dukakis ◽  
Nervous Breakdown ◽  
The Mind ◽  
Washington University ◽  
The Brain

In 1996 the Wall Street Journal noted, “The nervous breakdown, the affliction that has been a staple of American life and literature for more than a century, has been wiped out by the combined forces of psychiatry, pharmacology and managed care. But people keep breaking down anyway.” Indeed they do keep breaking down. Kitty Dukakis, wife of former presidential candidate Michael Dukakis, remembered lying in bed doing nothing. “I couldn’t get up and get dressed, but I couldn’t sleep either.” What was the matter with Kitty Dukakis and millions of sufferers like her? Depressed? What does psychiatry think? In psychiatry there are a few distinct, sharply defined diseases that would be difficult to miss, such as melancholia and catatonia. These tend to be psychotic illnesses, involving loss of contact with reality in the form of delusions and hallucinations, though not always. Then there is the great mass of nonpsychotic ill-defined illnesses whose labels are constantly changing and that are very common. Today these are called depression, oft en anxiety, and panic as well. These are all behavioral diagnoses, suggesting that the main problem is in the mind rather than the brain and body. Yet there is a tradition, now almost lost, of viewing psychiatric symptoms as a result of body processes, and it has always been convenient to speak of these as “nervous” diseases, even though much more of the body than the physical nerves may be involved. Writing in 1972, English psychiatrist Richard Hunter directed attention toward the body as a whole. “Many diseases are ushered in by a lowering of vitality which patients appreciate as irritability and depression. The mind is the most sensitive indicator of the state of the body. An abnormal mental state is equivalent to a physical sign of something going wrong in the brain.” The term symptom cluster is popular today, but that is jargonish, so let us call these patients “nervous.” Their distinguishing characteristic is that they do not have the “C” word, as Eli Robins at Washington University in St. Louis used to call it, meaning that they are not “crazy.”

scholarly journals Immune cells and CNS physiology: Microglia and beyond

2018 ◽  
Vol 216 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Geoffrey T. Norris ◽  
Jonathan Kipnis
Keyword(s):  
Central Nervous System ◽  
Immune Cells ◽  
Brain Function ◽  
Brain Parenchyma ◽  
The Body ◽  
Immune Repertoire ◽  
Perivascular Macrophages ◽  
The Central Nervous System ◽  
Cns Immunity ◽  
The Brain

Recent advances have directed our knowledge of the immune system from a narrative of “self” versus “nonself” to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. While the brain parenchyma is patrolled by perivascular macrophages and microglia, the meningeal spaces are supplied with a diverse immune repertoire. In this review, we posit that such partition allows for neuro–immune crosstalk to be properly tuned. Convention may imply that meningeal immunity is an ominous threat to brain function; however, recent studies have shown that its presence may instead be a steady hand directing the CNS to optimal performance.

scholarly journals Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

2018 ◽  
Vol 73 (Suppl. 5) ◽  
pp. 43-52 ◽  
Author(s):  
John D. Fernstrom
Keyword(s):  
Monosodium Glutamate ◽  
Safety Evaluation ◽  
The Body ◽  
Neuronal Function ◽  
Excitatory Neurotransmitter ◽  
Brain Functions ◽  
The Central Nervous System ◽  
Experimental Findings ◽  
The Brain ◽  
Amino Acid Glutamate

The non-essential amino acid glutamate participates in numerous metabolic pathways in the body. It also performs important physiologic functions, which include a sensory role as one of the basic tastes (as monosodium glutamate [MSG]), and a role in neuronal function as the dominant excitatory neurotransmitter in the central nervous system. Its pleasant taste (as MSG) has led to its inclusion as a flavoring agent in foods for centuries. Glutamate’s neurotransmitter role was discovered only in the last 60 years. Its inclusion in foods has necessitated its safety evaluation, which has raised concerns about its transfer into the blood ultimately increasing brain glutamate levels, thereby causing functional disruptions because it is a neurotransmitter. This concern, originally raised almost 50 years ago, has led to an extensive series of scientific studies to examine this issue, conducted primarily in rodents, non-human primates, and humans. The key findings have been that (a) the ingestion of MSG in the diet does not produce appreciable increases in glutamate concentrations in blood, except when given experimentally in amounts vastly in excess of normal intake levels; and (b) the blood-brain barrier effectively restricts the passage of glutamate from the blood into the brain, such that brain glutamate levels only rise when blood glutamate concentrations are raised experimentally via non-physiologic means. These and related discoveries explain why the ingestion of MSG in the diet does not lead to an increase in brain glutamate concentrations, and thus does not produce functional disruptions in brain. This article briefly summarizes key experimental findings that evaluate whether MSG in the diet poses a threat to brain function.

Macrophages in the Brain: Friends or Enemies?

Physiology ◽  
1994 ◽  
Vol 9 (2) ◽  
pp. 80-84 ◽  
Author(s):  
D Piani ◽  
DB Constam ◽  
K Frei ◽  
A Fontana
Keyword(s):  
Central Nervous System ◽  
Host Defense ◽  
The Body ◽  
Defense System ◽  
Tissue Destruction ◽  
Brain Macrophages ◽  
Host Defense System ◽  
The Central Nervous System ◽  
The Brain ◽  
Macrophage Lineage

Cells of the macrophage lineage are ubiquitously distributed in the body, including the central nervous system. They represent an essential host defense system to protect from infections. However, recent evidence indicates that brain macrophages may also be responsible for tissue destruction, including loss of neurons and demyelination.

The Pathogenesis of Somatic Disease in Mental Defectives

1951 ◽  
Vol 97 (409) ◽  
pp. 792-800 ◽  
Author(s):  
L. Crome
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Scientific Basis ◽  
The Body ◽  
Normal Person ◽  
Somatic Disease ◽  
The Central Nervous System ◽  
Mental Defectives ◽  
The Brain

The problems of the interdependence and unity of the brain and body have been put on a scientific basis by Pavlov and his successors. Bykov (1947) has, for example, been able to demonstrate that the cortex plays a leading part in the regulation of somatic processes, such as secretion of urine, blood pressure, peristalsis and metabolism. It is therefore reasonable to argue that lesions of the central nervous system will be reflected in the pathogenesis and course of morbid processes in the body. It does not follow, however, that this influence will necessarily be in the direction of greater lability, more rapid pathogenesis or more extensive destruction. The outstanding feature of the central nervous system is its plasticity and power of compensation. It is therefore possible and probable that those parts of the nervous system which remain intact will take over and compensate for the function of the lost ones. Emotion may, for example, lead to polyuria, but it does not follow that urinary secretion will be impaired in a leucotomized patient. The brain may well play an important part in the infective processes of a normal person, but the defence against infection in a microcephalic idiot may remain perfectly adequate, and may even be more effective than in a normal person, provided that the mechanism of the immunity and phagocytosis had been more fully mobilized in the course of his previous life.

scholarly journals Molecular Regulation of Striatal Development: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
A. E. Evans ◽  
C. M. Kelly ◽  
S. V. Precious ◽  
A. E. Rosser
Keyword(s):  
Complex Function ◽  
Dorsal Striatum ◽  
Higher Order ◽  
The Body ◽  
Specific Reference ◽  
Signalling Molecules ◽  
New Information ◽  
Brain Malformations ◽  
The Central Nervous System ◽  
The Brain

The central nervous system is composed of the brain and the spinal cord. The brain is a complex organ that processes and coordinates activities of the body in bilaterian, higher-order animals. The development of the brain mirrors its complex function as it requires intricate genetic signalling at specific times, and deviations from this can lead to brain malformations such as anencephaly. Research into how the CNS is specified and patterned has been studied extensively in chick, fish, frog, and mice, but findings from the latter will be emphasised here as higher-order mammals show most similarity to the human brain. Specifically, we will focus on the embryonic development of an important forebrain structure, the striatum (also known as the dorsal striatum or neostriatum). Over the past decade, research on striatal development in mice has led to an influx of new information about the genes involved, but the precise orchestration between the genes, signalling molecules, and transcription factors remains unanswered. We aim to summarise what is known to date about the tightly controlled network of interacting genes that control striatal development. This paper will discuss early telencephalon patterning and dorsal ventral patterning with specific reference to the genes involved in striatal development.

scholarly journals Metabolic phenotyping reveals a potential link between elevated faecal amino acids, diet and symptom severity in individuals with severe mental illness

2021 ◽  
Author(s):  
Jack Jansma ◽  
Rogier van Essen ◽  
Bartholomeus C.M. Haarman ◽  
Anastasia Chrysovalantou Chatziioannou ◽  
Jenny Borkent ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mental Illness ◽  
Severe Mental Illness ◽  
Symptom Severity ◽  
Psychiatric Symptoms ◽  
Mental Illnesses ◽  
Therapeutic Interventions ◽  
Schizophrenia Spectrum Disorders ◽  
Potential Link ◽  
The Brain

The brain-gut axis is increasingly recognized as an important contributing factor in the onset and progression of severe mental illnesses such as schizophrenia spectrum disorders and bipolar disorder. This study investigates associations between levels of faecal metabolites identified using 1H-NMR, clinical parameters, and dietary components of forty-two individuals diagnosed in a transdiagnostic approach to have severe mental illness. Faecal levels of the amino acids; alanine, leucine, and valine showed a significant positive correlation with psychiatric symptom severity as well as with dairy intake. Overall, this study proposes a diet-induced link between the brain-gut axis and the severity of psychiatric symptoms, which could be valuable in the design of novel dietary or therapeutic interventions to improve psychiatric symptoms.

scholarly journals Several forms of callitachykinins are distributed in the central nervous system and intestine of the blowfly Calliphora vomitoria.

1995 ◽  
Vol 198 (12) ◽  
pp. 2527-2536
Author(s):  
D R Nässel ◽  
M Y Kim ◽  
C T Lundquist
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Performance ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Additional Material ◽  
Immunoreactive Material ◽  
The Central Nervous System ◽  
Entire Central Nervous System ◽  
The Brain

We have examined the distribution of two tachykinin-related neuropeptides, callitachykinin I and II (CavTK-I and CavTK-II), isolated from whole-animal extracts of the blowfly Calliphora vomitoria. Extracts of dissected brains, thoracic-abdominal ganglia and midguts of adult blowflies and the entire central nervous system of larval flies were analysed by high performance liquid chromatography (HPLC) combined with enzyme-linked immunosorbent assay (ELISA) for the presence of CavTKs. To identify the two neuropeptides by HPLC, we used the retention times of synthetic CavTK-I and II as reference and detection with an antiserum raised to locustatachykinin II (shown here to recognise both CavTK-I and II). The brain contains only two immunoreactive components, and these have exactly the same retention times as CavTK-I and II. The thoracic-abdominal ganglia and midgut contain immunoreactive material eluting like CavTK-I and II as well as additional material eluting later. The larval central nervous system (CNS) contains material eluting like CavTK-I and II as well as a component that elutes earlier. We conclude that CavTK-I and II are present in all assayed tissues and that additional, hitherto uncharacterised, forms of tachykinin-immunoreactive material may be present in the body ganglia and midgut as well as in the larval CNS. An antiserum was raised to CavTK-II for immunocytochemistry. This antiserum, which was found to be specific for CavTK-II in ELISA, labelled all the neurones and midgut endocrine cells previously shown to react with the less selective locustatachykinin antisera. It is not clear, however, whether CavTK-I and II are colocalised in all LomTK-immunoreactive cells since there is no unambiguous probe for CavTK-I.

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