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Neurotransmitter, neuropeptide and gut peptide profile in PCOS-pathways contributing to the pathophysiology, food intake and psychiatric manifestations of PCOS.
Ilie, IR
Advances in clinical chemistry. 2020;:85-135
Abstract
Polycystic ovary syndrome (PCOS) is a major health problem with a heterogeneous hormone-imbalance and clinical presentation across the lifespan of women. Increased androgen production and abnormal gonadotropin-releasing hormone (GnRH) release and gonadotropin secretion, resulting in chronic anovulation are well-known features of the PCOS. The brain is both at the top of the neuroendocrine axis regulating ovarian function and a sensitive target of peripheral gonadal hormones and peptides. Current literature illustrates that neurotransmitters regulate various functions of the body, including reproduction, mood and body weight. Neurotransmitter alteration could be one of the reasons for disturbed GnRH release, consequently directing the ovarian dysfunction in PCOS, since there is plenty evidence for altered catecholamine metabolism and brain serotonin or opioid activity described in PCOS. Further, the dysregulated neurotransmitter and neuropeptide profile in PCOS could also be the reason for low self-esteem, anxiety, mood swings and depression or obesity, features closely associated with PCOS women. Can these altered central brain circuits, or the disrupted gut-brain axis be the tie that would both explain and link the pathogenesis of this disorder, the occurrence of depression, anxiety and other mood disorders as well as of obesity, insulin resistance and abnormal appetite in PCOS? This review intends to provide the reader with a comprehensive overview of what is known about the relatively understudied, but very complex role that neurotransmitters, neuropeptides and gut peptides play in PCOS. The answer to the above question may help the development of drugs to specifically target these central and peripheral circuits, thereby providing a valuable treatment for PCOS patients that present to the clinic with GnRH/LH hypersecretion, obesity or psychiatric manifestations.
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Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders.
Ng, J, Heales, SJ, Kurian, MA
Paediatric drugs. 2014;(4):275-91
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Abstract
Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa's syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.
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Nondopaminergic neurotransmission in the pathophysiology of Tourette syndrome.
Udvardi, PT, Nespoli, E, Rizzo, F, Hengerer, B, Ludolph, AG
International review of neurobiology. 2013;:95-130
Abstract
A major pathophysiological role for the dopaminergic system in Tourette's syndrome (TS) has been presumed ever since the discovery that dopamine-receptor antagonists can alleviate tics. Especially recent molecular genetic studies, functional imaging studies, and some rare postmortem studies have given more and more hints that other neurotransmitter systems are involved as well. Dysfunction in the dopamine metabolism-in particular during early development-might lead to counter-regulations in the other systems or vice versa. This chapter will give an overview of the studies that prove the involvement of other neurotransmitter systems such as the major monoaminergic neurotransmitters norepinephrine, serotonin, and histamine; the most important excitatory neurotransmitter, the amino acid glutamate; the major inhibitory neurotransmitter y-aminobutyric acid, as well as acetylcholine, endocannabinoid, corticoid; and others. These studies will hopefully lead to fundamental advances in the psychopharmacological treatment of TS. While tic disorders have been previously treated mainly with dopamine antagonists, some authors already favor alpha-agonists. Clinical trials with glutamate agonists and antagonists and compounds influencing the histaminergic system are currently being conducted. Since the different neurotransmitter systems consist of several receptor subtypes which might mediate different effects on locomotor activity, patients with TS may respond differentially to selective agonists or antagonists. Effects of agonistic or antagonistic compounds on tic symptoms might also be dose dependent. Further studies will lead to a broader spectrum of psychopharmacological treatment options in TS.
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Congestive heart failure: pathophysiologic consequences of neurohormonal activation and the potential for recovery: part I.
Dube, P, Weber, KT
The American journal of the medical sciences. 2011;(5):348-51
Abstract
What begins with a failing heart, unable to sustain adequate renal perfusion and metabolic needs of the tissues it serves becomes a systemic illness whose origins are rooted in neurohormonal activation. This unwanted homeostatic stressor response, an adaptation gone awry, has pathologic consequences. It involves endocrine properties of effector hormones arising from the adrenergic and renin-angiotensin-aldosterone systems. The clinical syndrome congestive heart failure (CHF) has its symptoms and signs rooted in a hormonally mediated salt-avid state. The ensuing salt and water retention includes the expansion of the intravascular space with consequent central and systemic venous congestion that, respectively, involves the heart and lungs, the liver, gut and kidneys and ultimately the extravascular space. Other pathophysiologic outcomes contribute to a proinflammatory CHF phenotype. These include an ongoing adverse remodeling of the failing heart with lost necrotic cardiomyocytes and a consequent replacement fibrosis; wasting of soft tissues and resorption of bone; dyshomeostasis of extra- and intracellular mono- and divalent cations that contributes to the appearance of oxidative stress coupled with compromised antioxidant defenses and an immunostimulatory state with activated lymphocytes and monocytes elaborating proinflammatory cytokines. In this 2-part review, the pathophysiologic consequences associated with neurohormonal activation in CHF will first be reviewed. Next, several lines of evidence are considered that raise the hitherto unfathomable prospect for recovery from CHF, including reverse remodeling of the heart and systemic tissues.
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Inherited disorders of neurotransmitters in children and adults.
Pearl, PL, Capp, PK, Novotny, EJ, Gibson, KM
Clinical biochemistry. 2005;(12):1051-8
Abstract
Inherited disorders of neurotransmitters are a group of neurometabolic syndromes attributable to a primary disturbance of neurotransmitter metabolism or transport. This is an enlarging group of recognized disorders requiring specialized diagnostic procedures for detection. This review considers clinical disorders of biopterin, catecholamines, serotonin, glycine, pyridoxine, and GABA metabolism. Newly described syndromes such as cerebral folate deficiency and pyridoxal-5-phosphate dependency are included. The disorders of the metabolic pathways of biopterin, catecholamines, and serotonin are linked due to their common synthetic components. Glycine encephalopathy represents an enlarging phenotype related to abnormalities of the glycine degradative cleavage system. Both pyridoxine and pyridoxal-5-phosphate dependency need to be considered in refractory neonatal seizures. The most common disorder of GABA metabolism is SSADH deficiency, which has a broad phenotype of mental retardation, epilepsy, ataxia, and hyporeflexia and which invokes the combined problems of elevated brain GABA and GHB.