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Neuro–Endocrine–Immune Dysfunction in the Chronic Pain Patient
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Another pathway used by the central nervous system to communicate with the immune system is via a neuropeptidergic pathway. When nociceptors are activated, the axons themselves release neuropeptides that have been noted to further impact the activity of the neurons. Substances such as CGRP, SP, adrenomedullin, neurokinin A and BV, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) are examples of these type of neuropeptides. These neuropeptides also modulate innate and adaptive immune cells. Mast cell degranulation increases. Neutrophil activation and chemotaxis increase. T-cell activation and proliferation increase. Macrophage activation and phagocytosis capability increase.8
Opioids and Induction of Ovulation: Mediation by Neuropeptide Y
Published in Craig A. Johnston, Charles D. Barnes, Brain-Gut Peptides and Reproductive Function, 2020
S.P. Kalra, L.G. Allen, A. Sahu, W.R. Crowley
Subsequently, in August-September 1983, we became aware of another member of the PP family, NPY, a biologically active peptide of neural origin with a distribution pattern in the rat brain similar to that of PP (Allen et al., 1983; Guy et al., 1983; Tatemoto, 1982; Tatemoto et al., 1982). Consequently, from December 1983 onwards we studied the effects of intraventricular NPY on LH release. Similar to NE and hPP, NPY inhibited LH release in ovx rats and stimulated LH release in a dose-related fashion in ovarian steroid-primed ovx rats (Kalra and Crowley, 1984b). Thus, the concept that NPY may indeed be an endogenous excitatory neuropeptidergic system, functionally linked with the LHRH-LH axis in gonad-intact rats, was advanced. These formulations were validated directly in gonad-intact rats (Allen et al., 1985; Rodriguez-Sierra et al., 1987). In line with our findings, McDonald et al. (1985) reported an inhibition of LH release by NPY in ovx rats, but contrary to our hypothesis (Kalra and Crowley, 1984a,b), implied that like avian PP, NPY may normally act as an inhibitory hypothalamic peptide in the regulation of LH release.
Animal Models of Ligament Repair
Published in Yuehuei H. An, Richard J. Friedman, Animal Models in Orthopaedic Research, 2020
Jason J. McDougall, Robert C. Bray
Immunohistochemistry has been used to detect neuropeptidergic nerve fibers in normal and healing MCLs.61,62 Neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) are pro-inflammatory agents released from the terminals of afferent nerves and which cause vasodilatation and protein extravasation. In addition to their haemodynamic effects, neuropeptides possess trophic properties causing neovascularization and tissue remodeling by promoting fibroblast differentiation. Experiments have shown62 that six weeks after gap injury, SP and CGRP immunoreactivity is increased in the healing scar tissue although the nerves appear truncated and tangled (Figure 3). Increased presence of peptidergic nerves in the MCL may relate to the sound healing potential of this structure.
Efficacy, safety, and tolerability of ulotaront (SEP-363856, a trace amine-associated receptor 1 agonist) for the treatment of schizophrenia and other mental disorders: a systematic review of preclinical and clinical trials
Published in Expert Opinion on Investigational Drugs, 2023
Gia Han Le, Emily S. Gillissie, Taeho Greg Rhee, Bing Cao, Yazen Alnefeesi, Ziji Guo, Joshua D. Di Vincenzo, Muhammad Youshay Jawad, Andrew M. March, Ranuk Ramachandra, Leanna M.W. Lui, Roger S. McIntyre
Since antipsychotic use has been associated with numerous adverse effects, there has been an emerging consensus on the need for novel treatment strategies to treat the symptoms of schizophrenia spectrum disorder with enhanced efficacy and safety [24]. Focus has been redirected toward discovering and developing pharmacological agents that are non-D2 receptor-based, including treatments that are based on serotonergic, glutamatergic, ‘cholinergic, neuropeptidergic, hormone-based, other dopaminergic, metabolic, naturopathic, histaminergic, inflammation-based, and miscellaneous mechanisms’ [25]. For example, xanomeline is a muscarinic acetylcholine receptor M1/M4 agonist that has antipsychotic properties and is non-D2 receptor-based but has been associated with cholinergic adverse events [26,27]. In a double-blind, phase II clinical trial, Brannan et al. [27] administered trospium, a peripherally restricted muscarinic receptor antagonist, with xanomeline to patients with schizophrenia to reduce peripheral cholinergic effects of xanomeline and investigate the efficacy and safety of combining these agents for the treatment of schizophrenia. In a 5-week trial, a greater decrease in the Positive and Negative Syndrome Scale (PANSS) total score was observed in patients receiving xanomeline-trospium (−17.4 points) compared to the placebo (−5.9 points) (least-squares mean difference = −11.6 points; 95% CI, −16.1 to −7.1; p < 0.001) [27]. Despite reducing symptoms of schizophrenia, xanomeline-trospium was associated with cholinergic and anticholinergic adverse events [27].
Unraveiling the correlation among neurodevelopmental and inflammatory biomarkers in patients with chronic schizophrenia
Published in Nordic Journal of Psychiatry, 2022
João V. Nani, Priscila G. C Almeida, Cristiano Noto, Rodrigo A. Bressan, Elisa Brietzke, Mirian A. F Hayashi
Alterations in the neuropeptidergic system in psychiatric disorders (PD) have been reported by many [1], and its ability to modulate the homeostasis of ‘classic’ neurotransmitters, such as dopamine, was demonstrated [13,14]. In addition, we have suggested the involvement of Ndel1 enzyme activity in the pathophysiology of SCZ, in different ways, as for instance, the Ndel1 ability to cleave neuropeptides and to form complex with cytoskeletal proteins were both shown to be essential for neurite outgrowth and brain formation, suggesting therefore, a crucial role of Ndel1 for neurodevelopment [15,16]. In fact, null knockout for Ndel1 is lethal at early embryonic phase, while heterozygosis resulted in histological defects consistent with mild neuronal migration defects [17]. Also, conditional deletion also leads to brain structure and connectivity abnormalities [18,19], as well as decreased Ndel1 activity was correlated with abnormal dopaminergic signaling and disrupted neurodevelopment [2].
What have we learnt from past failures in Alzheimer’s disease drug discovery?
Published in Expert Opinion on Drug Discovery, 2022
The neuropathological phenotype of AD is characterized by age-related dendritic desarborization, microglial reactivity, astrogliosis, and neuronal loss in critical regions of the CNS, with the presence of extracellular deposits of aggregated β-amyloid (Aβ) in neuritic plaques and vessels, formed due to abnormal processing of APP, together with synergistic intracellular inclusions of neurofibrillary tangles (NFTs), resulting from the hyperphosphorylation of tau protein in microtubules and neurofilaments. Among neurochemical findings, as a consequence of neurodegeneration, AD brains exhibit neurotransmitter deficits (cholinergic, noradrenergic, dopaminergic, serotonergic, glutamatergic, GABAergic, neuropeptidergic), neurotrophic alterations, biochemical markers of neuroinflammatory reactions and disruption of lipid rafts due to oxidative stress-induced lipid peroxidation. All these deleterious events are accompanied by hypoperfusion-related cerebrovascular damage [5–11].