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Neurotrophic factors

Gesine Paul, Aideen M Sullivan
Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the development of a therapy that can slow or halt disease progression. Extensive pre-clinical research has provided evidence for the neurorestorative properties of several growth factors, yet only a few have been evaluated in clinical studies. Attempts to achieve neuroprotection by addressing cell-autonomous mechanisms and targeting dopaminergic neurons have been disappointing. Four different trophic factors have so far entered clinical trials in PD: glial cell line-derived growth factor, its close structural and functional analog neurturin, platelet-derived growth factor and cerebral dopaminergic neurotrophic factor...
August 13, 2018: European Journal of Neuroscience
Ryan D Shepard, Shawn Gouty, Haifa Kassis, Aylar Berenji, William Zhu, Brian M Cox, Fereshteh S Nugent
Severe early life stressors increase the probability of developing psychiatric disorders later in life through modifications in neuronal circuits controlling brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling from the ventral tegmental area (VTA) through changes at GABAergic synapses that were reversible by in vitro histone deacetylase (HDAC) inhibition which led to restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and subsequently recovered GABAergic plasticity (Authement et al...
August 10, 2018: Experimental Neurology
André Luis Bombeiro, Bruna Toledo Nunes Pereira, Alexandre Leite Rodrigues de Oliveira
Peripheral nerve injuries severely impair patients' quality of life since full recovery is seldom achieved. Upon axonal disruption, the distal nerve stump undergoes fragmentation, and myelin breaks down; the subsequent regeneration progression is dependent on cell debris removal. In addition to tissue clearance, macrophages release angiogenic and neurotrophic factors that contribute to axon growth. Based on the importance of macrophages for nerve regeneration, especially during the initial response to injury, we treated mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) at various intervals after sciatic nerve crushing...
August 11, 2018: European Journal of Neuroscience
Sun-Ji Park, Yeawon Kim, Ying Maggie Chen
The advent of next-generation sequencing (NGS) in recent years has led to a rapid discovery of novel or rare genetic variants in human kidney cell genes, which is transforming the risk assessment, diagnosis, and treatment of kidney disease. Mutations may lead to protein misfolding, disruption of protein trafficking, and endoplasmic reticulum (ER) retention. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and unfolded protein response. Mutations in nephrin (NPHS1), podocin (NPHS2), laminin β2 (LAMB2), and α-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV α chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease...
August 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Mingdan You, Weijia Gu, Mei Li, Zhenmin Qiu, Siyao Li, Zhixin Jiang, Dianqi Yao, Yuanyuan Xu, Yi Wang
Nonylphenol (NP) is a commercially produced nonionic surfactant that has become a global environmental pollutant due to poor biodegradability. Many studies have confirmed that NP has detrimental effects on the central nervous system. However, the damaging roles of NP on the cerebellum and the underlying mechanisms remain unclear. Therefore, we investigated the effects of perinatal exposure to NP on cerebellar Purkinje cell (PC) dendrites and explored the potential mechanism involved. The animal model of perinatal exposure to NP was established by orally administering dams with either corn oil or NP (10, 50, or 100 mg/kg) during pregnancy and lactation...
August 3, 2018: Chemosphere
Jaśmina Arabska, Anna Łucka, Dominik Strzelecki, Adam Wysokiński
AIM: Neurotrophin-3 (NT-3) is a neurotrophic factor responsible for promoting development, survival and function of neurons. NT-3 may be involved in the etiopathology of schizophrenia and mood disorders. However it must be cleared up if changes of NT-3 level are associated with schizophrenia itself or are secondary to certain symptoms (e.g. negative or depressive). The aim of this study was to examine whether the presence of negative or depressive symptoms affects peripheral NT-3 concentration in patients with schizophrenia...
August 8, 2018: Neuroscience Letters
Marlena Wosiski-Kuhn, Mihail Bota, Christina A Snider, Steven P Wilson, Kannan U Venkataraju, Pavel Osten, Alexis M Stranahan
Diabetes increases adrenal steroids in humans and animal models, but potential interactions with psychological stress remain poorly understood. Diabetic rodents exhibit anxiety and reductions in hippocampal brain-derived neurotrophic factor (BDNF) expression, and these studies investigated whether loss of BDNF-driven hippocampal activity promotes anxiety and disinhibits the HPA axis. Mice with genetic obesity and diabetes (db/db) received intrahippocampal injections of lentivirus for BDNF overexpression (db/db-BDNFOE), and Wt mice received lentiviral constructs for BDNF knockdown (Wt-BDNFKD)...
August 11, 2018: Hippocampus
Dominique Richardson, Jaakko Itkonen, Julia Nievas, Arto Urtti, Marco G Casteleijn
The use of living cells for the synthesis of pharmaceutical proteins, though state-of-the-art, is hindered by its lengthy process comprising of many steps that may affect the protein's stability and activity. We aimed to integrate protein expression, purification, and bioconjugation in small volumes coupled with cell free protein synthesis for the target protein, ciliary neurotrophic factor. Split-intein mediated capture by use of capture peptides onto a solid surface was efficient at 89-93%. Proof-of-principle of light triggered release was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA)...
August 10, 2018: Scientific Reports
Kheng Siang Ted Ng, Angelia Sia, Maxel K W Ng, Crystal T Y Tan, Hui Yu Chan, Chay Hoon Tan, Iris Rawtaer, Lei Feng, Rathi Mahendran, Anis Larbi, Ee Heok Kua, Roger C M Ho
The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months...
August 9, 2018: International Journal of Environmental Research and Public Health
R Corne, C Leconte, M Ouradou, V Fassina, Y Zhu, E Déou, V Besson, M Plotkine, C Marchand-Leroux, R Mongeau
Mild traumatic brain injury (TBI) is a major risk factor for post-traumatic stress disorder (PTSD), and both disorders share common symptoms and neurobiological defects. Relapse after successful treatment, known as long-term fear resurgence, is common in PTSD patients and a major therapeutic hurdle. We induced a mild focal TBI by controlled cortical impact (CCI) in male C57BL/6 J mice and used fear conditioning to assess PTSD-like behaviors and concomitant alterations in the fear circuitry. We found for the first time that mild TBI, and to a lesser extent sham (craniotomy), mice displayed a spontaneous resurgence of conditioned fear when tested for fear extinction memory recall, despite having effectively acquired and extinguished conditioned fear 6 weeks earlier in the same context...
August 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
B D Fulop, B Sandor, E Szentleleky, E Karanyicz, D Reglodi, B Gaszner, R Zakany, H Hashimoto, T Juhasz, A Tamas
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with neuroprotective and neurotrophic effects. This suggests its influence on the development of teeth, which are, similarly to the nervous system, ectoderm and neural crest derivatives. Our earlier studies have shown morphological differences between wild-type (WT) and PACAP-deficient mice, with upregulated sonic hedgehog (SHH) signaling in the lack of PACAP. Notch signaling is a key element of proper tooth development by regulating apoptosis and cell proliferation...
August 10, 2018: Journal of Molecular Neuroscience: MN
Cristy Phillips, Atoossa Fahimi
Physical activity-a lifestyle factor that is associated with immune function, neuroprotection, and energy metabolism-modulates the cellular and molecular processes in the brain that are vital for emotional and cognitive health, collective mechanisms that can go awry in depression. Physical activity optimizes the stress response, neurotransmitter level and function (e.g., serotonergic, noradrenergic, dopaminergic, and glutamatergic), myokine production (e.g., interleukin-6), transcription factor levels and correlates [e...
2018: Frontiers in Neuroscience
Alexa Alves de Moraes, Cayo Antônio Soares de Almeida, Guilherme Lucas, José Antonio Thomazini, Aline Santos DeMaman
OBJECTIVE: This study aims to investigate morphological alterations caused by partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity swimming training as therapeutic strategy for nerve regeneration. METHODS: A number of 30 male adult mice were equally divided in control, 14 days after PNL (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days) and 5-week exercise training after 7 days post-lesion (PNL trained 35 days) groups...
August 9, 2018: Neurological Research
I Muñoz-Cobo, M M Erburu, C Zwergel, R Cirilli, A Mai, S Valente, E Puerta, Rosa M Tordera
RATIONALE: Antidepressant action has been linked to increased synaptic plasticity in which epigenetic mechanisms such as histone posttranslational acetylation could be involved. Interestingly, the histone deacetylases HDAC5 and SIRT2 are oppositely regulated by stress and antidepressants in mice prefrontal cortex (PFC). Besides, the neuroblastoma SH-SY5Y line is an in vitro neuronal model reliable to study drug effects with clear advantages over animals. OBJECTIVES: We aimed to characterize in vitro the role of HDAC5 and SIRT2 in antidepressant regulation of neuroplasticity...
August 8, 2018: Psychopharmacology
Bo He, Dan Xu, Chong Zhang, Li Zhang, Hui Wang
The higher risk of adult neuropsychiatric diseases in individuals with low fetal birth weight may be related to brain-derived neurotrophic factor (BDNF) signaling pathway inhibition. Here, we investigated whether prenatal food restriction (PFR) induces neurobehavioral alterations in adult female offspring and explored the underlying intrauterine programming mechanism. Pregnant Wistar rats in the PFR group were fed 50% of the daily food intake of control rats from gestational day (GD) 11 to 20; some pregnant rats were sacrificed at GD20, and the remaining female pups had normal delivery and were fed a post-weaning high-fat diet (HFD) and half of them were exposed to an unpredictable chronic stress (UCS) from postnatal week (PW) 21...
March 1, 2018: Toxicology Research
Kärt Mätlik, Vootele Võikar, Carolina Vilenius, Natalia Kulesskaya, Jaan-Olle Andressoo
Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson's disease (PD). However, how endogenous GDNF influences dopamine system function and animal behavior is not fully understood. We recently generated GDNF hypermorphic mice that express increased levels of endogenous GDNF from the native locus, resulting in augmented function of the nigrostriatal dopamine system...
August 8, 2018: Scientific Reports
Pei-Yi Lin, Ege T Kavalali, Lisa M Monteggia
Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), regulate long-term potentiation (LTP) in the hippocampus, although the sites of BDNF-TrkB receptors in this process are controversial. We used a viral-mediated approach to delete BDNF or TrkB specifically in CA1 and CA3 regions of the Schaffer collateral pathway. Deletion of BDNF in CA3 or CA1 revealed that presynaptic BDNF is involved in LTP induction, while postsynaptic BDNF contributes to LTP maintenance...
August 7, 2018: Cell Reports
Jie Gao, Bingrui Xiong, Bo Zhang, Shan Li, Niannian Huang, Gaofeng Zhan, Riyue Jiang, Ling Yang, Yeshun Wu, Liying Miao, Bin Zhu, Chun Yang, Ailin Luo
Peripheral immune activation could cause neuroinflammation, leading to a series of central nervous system (CNS) disorders, such as spatial learning and memory dysfunction. However, its pathogenic mechanism and therapeutic strategies are not yet determined. The present study aimed to investigate the therapeutic effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced spatial learning and memory dysfunction, and tried to elucidate its relationship with the role of hippocampal brain-derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling pathway...
August 4, 2018: Neuroscience
Thekkuttuparambil Ananthanarayanan Ajith
Dietary long chain polyunsaturated fatty acids belong to omega (ω)-3, -6 or -9 series. Both experimental and clinical studies demonstrated the beneficial effect of ω -3 fatty acids of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) against human ailments including cardiovascular diseases and rheumatoid arthritis. They are metabolized in cyclooxygenase and lipooxygenase pathways and also by cytochrome P450 isozymes. Biological importance of DHA in the development of brain and retina are established as well...
August 7, 2018: Current Clinical Pharmacology
Еlena V Mitroshina, Tatiana A Mishchenko, Alexandra V Usenko, Ekaterina A Epifanova, Roman S Yarkov, Maria S Gavrish, Alexey A Babaev, Maria V Vedunova
Brain-derived neurotrophic factor (BDNF) is one of the key signaling molecules that supports the viability of neural cells in various brain pathologies, and can be considered a potential therapeutic agent. However, several methodological difficulties, such as overcoming the blood⁻brain barrier and the short half-life period, challenge the potential use of BDNF in clinical practice. Gene therapy could overcome these limitations. Investigating the influence of viral vectors on the neural network level is of particular interest because viral overexpression affects different aspects of cell metabolism and interactions between neurons...
August 5, 2018: International Journal of Molecular Sciences
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