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Neuronal peptides

Pinelopi Pliota, Vincent Böhm, Florian Grössl, Johannes Griessner, Ornella Valenti, Klaus Kraitsy, Joanna Kaczanowska, Manuel Pasieka, Thomas Lendl, Jan M Deussing, Wulf Haubensak
Survival relies on optimizing behavioral responses through experience. Animals often react to acute stress by switching to passive behavioral responses when coping with environmental challenge. Despite recent advances in dissecting mammalian circuitry for Pavlovian fear, the neuronal basis underlying this form of non-Pavlovian anxiety-related behavioral plasticity remains poorly understood. Here, we report that aversive experience recruits the posterior paraventricular thalamus (PVT) and corticotropin-releasing hormone (CRH) and sensitizes a Pavlovian fear circuit to promote passive responding...
June 14, 2018: Molecular Psychiatry
Yan Jin, Qiuyun Tu, Min Liu
The present study aimed to investigate the expression of microRNA (miR)‑125b in patients with Alzheimer's disease (AD) and to determine its potential role in AD. Mouse neuroblastoma Neuro2a APPSwe/Δ9 cells were used to generate an in vitro AD model. The results demonstrated that the expression levels of miR‑125b were markedly increased in patients with AD compared with in the normal group. In addition, overexpression of miR‑125b significantly inhibited cell proliferation, induced apoptosis, and enhanced inflammation and oxidative stress in an in vitro model of AD model...
June 13, 2018: Molecular Medicine Reports
Serena Stanga, Liliana Brambilla, Bernadette Tasiaux, Anh H Dang, Adrian Ivanoiu, Jean-Noël Octave, Daniela Rossi, Vincent van Pesch, Pascal Kienlen-Campard
The current inability of clinical criteria to accurately identify the "at-risk group" for Amyotrophic Lateral Sclerosis (ALS) development as well as its unknown etiology are fueling the interest in biomarkers aimed at completing clinical approaches for the diagnosis. The Glial cell line-derived neurotrophic factor (GDNF) is a diffusible peptide critically involved in neuronal differentiation and survival. GDNF is largely studied in various neurological and neuromuscular diseases, with a great interest in the peripheral nervous system (PNS)...
2018: Frontiers in Neurology
Erin E Congdon, Einar M Sigurdsson
Alzheimer disease (AD) is the most common form of dementia. Pathologically, AD is characterized by amyloid plaques and neurofibrillary tangles in the brain, with associated loss of synapses and neurons, resulting in cognitive deficits and eventually dementia. Amyloid-β (Aβ) peptide and tau protein are the primary components of the plaques and tangles, respectively. In the decades since Aβ and tau were identified, development of therapies for AD has primarily focused on Aβ, but tau has received more attention in recent years, in part because of the failure of various Aβ-targeting treatments in clinical trials...
June 12, 2018: Nature Reviews. Neurology
Ana I Duarte, Marie Sjögren, Maria S Santos, Catarina R Oliveira, Paula I Moreira, Maria Björkqvist
Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition...
June 12, 2018: Scientific Reports
Auriane Corbière, Marie-Laure Walet-Balieu, Philippe Chan, Magali Basille-Dugay, Julie Hardouin, David Vaudry
The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood...
June 12, 2018: Molecular & Cellular Proteomics: MCP
Akiko Sumitomo, Hiroshi Yukitake, Kazuko Hirai, Kouta Horike, Keisho Ueta, Youjin Chung, Eiji Warabi, Toru Yanagawa, Shiho Kitaoka, Tomoyuki Furuyashiki, Shuh Narumiya, Tomoo Hirano, Minae Niwa, Etienne Sibille, Takatoshi Hikida, Takeshi Sakurai, Koko Ishizuka, Akira Sawa, Toshifumi Tomoda
Autophagy plays an essential role in intracellular degradation and maintenance of cellular homeostasis in all cells, including neurons. Although a recent study reported a copy number variation of Ulk2, a gene essential for initiating autophagy, associated with a case of schizophrenia (SZ), it remains to be studied whether Ulk2 dysfunction could underlie the pathophysiology of the disease. Here we show that Ulk2 heterozygous (Ulk2+/-) mice have upregulated expression of sequestosome-1/p62, an autophagy-associated stress response protein, predominantly in pyramidal neurons of the prefrontal cortex (PFC), and exhibit behavioral deficits associated with the PFC functions, including attenuated sensorimotor gating and impaired cognition...
June 8, 2018: Human Molecular Genetics
Nilima A Vyas, Sushma B Singh, Avinash S Kumbhar, Dnyanesh S Ranade, Gulshan R Walke, Prasad P Kulkarni, Vinod Jani, Uddhavesh B Sonavane, Rajendra R Joshi, Srikanth Rapole
Two heteronuclear ruthenium(II)-platinum(II) complexes [Ru(bpy)2 (BPIMBp)PtCl2 ]2+ (3) and [Ru(phen)2 (BPIMBp)PtCl2 ]2+ (4), where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and BPIMBp = 1,4'-bis[(2-pyridin-2-yl)-1H-imidazol-1-ylmethyl]-1,1'-biphenyl, have been designed and synthesized from their mononuclear precursors [Ru(bpy)2 (BPIMBp)]2+ (1) and [Ru(phen)2 (BPIMBp)]2+ (2) as multitarget molecules for Alzheimer's disease (AD). The inclusion of the cis-PtCl2 moiety facilitates the covalent interaction of Ru(II) polypyridyl complexes with amyloid β (Aβ) peptide...
June 12, 2018: Inorganic Chemistry
Bethania Mongi-Bragato, María P Avalos, Andrea S Guzmán, Flavia A Bollati, Liliana M Cancela
Enkephalin expression is high in mesocorticolimbic areas associated with psychostimulant-induced behavioral and neurobiological effects, and may also modulate local neurotransmission in this circuit network. Psychostimulant drugs, like amphetamine and cocaine, significantly increase the content of enkephalin in these brain structures, but we do not yet understand the specific significance of this drug-induced adaptation. In this review, we summarize the neurochemical and molecular mechanism of psychostimulant-induced enkephalin activation in mesocorticolimbic brain areas, and the contribution of this opioid peptide in the pivotal neuroadaptations and long-term behavioral changes underlying psychostimulant addiction...
2018: Frontiers in Psychiatry
Seung Pil Yun, Tae-In Kam, Nikhil Panicker, SangMin Kim, Yumin Oh, Jong-Sung Park, Seung-Hwan Kwon, Yong Joo Park, Senthilkumar S Karuppagounder, Hyejin Park, Sangjune Kim, Nayeon Oh, Nayoung Alice Kim, Saebom Lee, Saurav Brahmachari, Xiaobo Mao, Jun Hee Lee, Manoj Kumar, Daniel An, Sung-Ung Kang, Yunjong Lee, Kang Choon Lee, Dong Hee Na, Donghoon Kim, Sang Hun Lee, Viktor V Roschke, Shane A Liddelow, Zoltan Mari, Ben A Barres, Valina L Dawson, Seulki Lee, Ted M Dawson, Han Seok Ko
Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases1,2 . Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease3-13 ...
June 11, 2018: Nature Medicine
Biancamaria Farina, Mattia Sturlese, Fabiola Mascanzoni, Andrea Caporale, Alessandra Monti, Gianluigi Di Sorbo, Roberto Fattorusso, Menotti Ruvo, Nunzianna Doti
The complex formation between the proteins Apoptosis Inducing Factor (AIF) and Cyclophilin A (CypA) following oxidative stress in neuronal cells has been suggested as a main target for reverting ischemia-stroke damage. Recently, a peptide encompassing AIF residues 370-394 has been developed to target the AIF-binding site on CypA, to prevent the association between the two proteins and suppress glutamate-induced cell death in neuronal cells. Using a combined approach based on NMR spectroscopy, synthesis and in vitro testing of all Ala-scan mutants of the peptide and molecular docking/molecular dynamics, we have generated a detailed model of the AIF(370-394)/CypA complex...
June 11, 2018: Biochemical Journal
Yuya Kawarai, Sumihisa Orita, Junichi Nakamura, Shuichi Miyamoto, Miyako Suzuki, Kazuhide Inage, Shigeo Hagiwara, Takane Suzuki, Takayuki Nakajima, Tsutomu Akazawa, Seiji Ohtori
The aim of this study was to investigate the local production of proinflammatory cytokines, pain- related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy-five Sprague Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N =25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF-α, immunoreactive (-ir) neurons for calcitonin gene-related peptide (CGRP) and growth associated protein-43 (GAP-43) in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule-1 (Iba-1) in the dorsal horn of spinal cord, on post-induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point)...
June 11, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Michael Thoene, Janusz Godlewski, Liliana Rytel, Ewa Dzika, Ewa Bejer-Oleńska, Joanna Wojtkiewicz
INTRODUCTION: Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver...
June 11, 2018: Folia Histochemica et Cytobiologica
Matthew Randesi, Yan Zhou, Sanoara Mazid, Shannon C Odell, Jason D Gray, J Correa da Rosa, Bruce S McEwen, Teresa A Milner, Mary Jeanne Kreek
Opioid peptides and their receptors re-organize within hippocampal neurons of female, but not male, rats following chronic immobilization stress (CIS) in a manner that promotes drug-related learning. This study was conducted to determine if there are also sex differences in gene expression in the hippocampus following CIS. Adult female and male rats were subjected to CIS (30 min/day) for 10 days. Twenty-four hours after the last stressor, the rats were euthanized, the brains were harvested and the medial (dentate gyrus/CA1) and lateral (CA2/CA3) dorsal hippocampus were isolated...
February 2018: Neurobiology of Stress
Louise O'Keefe, Donna Denton
Autophagy is a conserved catabolic pathway that involves the engulfment of cytoplasmic components such as large protein aggregates and organelles that are delivered to the lysosome for degradation. This process is important in maintaining neuronal function and raises the possibility of a role for autophagy in neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent form of these diseases and is characterized by the accumulation of amyloid plaques in the brain which arise due to the misfolding and aggregation of toxic peptides, including amyloid beta (A β )...
2018: BioMed Research International
Adela Bernabeu-Zornoza, Raquel Coronel, María Lachgar, Charlotte Palmer, Isabel Liste
The amyloid -β peptide (Aβ) is the main component of the amyloid plaques in Alzheimer's disease (AD). It has been widely demonstrated that Aβ is toxic to neurons and is associated with AD pathology. However, Aβ also appears to have an important biological function both in the adult brain and throughout embryonic development of the nervous system, acting as a trophic factor at low concentrations.It is known that Neural Stem Cells (NSCs) are capable of self-renewal and differentiate into functional glial and neuronal cells...
2018: Methods in Molecular Biology
Susana Brun, Nicolas Schall, Srinivasa Reddy Bonam, Kévin Bigaut, Ayikoe-Guy Mensah-Nyagan, Jérôme de Sèze, Sylviane Muller
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or misfolded proteins, it has not been addressed whether autophagy, a central "clearance" system delivering damaged intracellular components to lysosomes, is affected in CIDP. The focus of the present investigation was therefore to determine if some defects exist in autophagy processes in this setting and if they can be corrected or minimized using an appropriate treatment targeting this survival pathway...
June 5, 2018: Journal of Autoimmunity
Christine Hellwig, Marta Barenys, Jenny Baumann, Kathrin Gassmann, Laura Casanellas, Gerhard Kauer, Ellen Fritsche
Human neural progenitor cells cultured as neurospheres are a promising tool for developmental neurotoxicity testing in vitro. In order to obtain a human cell-based tissue culture system as close to the organ as possible, it is desirable to improve the spatial organization of the "Neurosphere Assay" and use 3D scaffolds to better mimic the in vivo three dimensional cell microenvironment. For this reason we have established the conditions for short-term culture (up to 6 days) in matrigel or in IKVAV-3 peptide-functionalized hydrogels, and for long-term culture (>25 days) in IKVAV-3 peptide-functionalized hydrogels showing that these conditions support human neural progenitor cells' migration, differentiation to neurons and formation of neuronal networks...
June 5, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Jingjing Jia, Ting Zhang, Jieshan Chi, Xiaoma Liu, Jingjing Sun, Qizhi Xie, Sijia Peng, Changyan Li, Li Yi
CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2 @PAA-LXW7, a new compound that couples CeO2 @PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2 O2 -induced NGF-differentiated PC12 cells...
June 7, 2018: Neurochemical Research
Elena A Silantyeva, Wafaa Nasir, Jacqueline Carpenter, Olivia Manahan, Matthew L Becker, Rebecca K Willits
Substrates for embryonic stem cell culture are typified by poorly defined xenogenic, whole proteins or cellular components that are difficult and expensive to generate, characterize, and recapitulate. Herein, the generation of well-defined scaffolds of Gly-Tyr-Ile-Gly-Ser-Arg (GYIGSR) peptide-functionalized poly(ε-caprolactone) (PCL) aligned nanofibers are used to accelerate the neural lineage commitment and differentiation of D3 mouse embryonic stem cells (mESCs). Gene expression trends and immunocytochemistry analysis were similar to laminin-coated glass, and indicated an earlier differentiation progression than D3 mESCs on laminin...
June 4, 2018: Acta Biomaterialia
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