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https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#1
REVIEW
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28228583/food-responsiveness-regulates-episodic-behavioral-states-in-caenorhabditis-elegans
#2
Richard J McCloskey, Anthony D Fouad, Matthew A Churgin, Christopher Fang-Yen
Animals optimize survival and reproduction in part through control of behavioral states, which depend on the organism's internal and external environments. In the nematode C. elegans, a variety of behavioral states have been described, including roaming, dwelling, quiescence, and episodic swimming. These states have been considered in isolation, under varied experimental conditions, making it difficult to establish a unified picture of how they are regulated. Using long-term imaging, we examined C. elegans episodic behavioral states under varied mechanical and nutritional environments...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28227432/colony-size-effect-on-neural-differentiation-of-embryonic-stem-cells-microprinted-on-stromal-cells
#3
Ramila Joshi, James Buchanan, Hossein Tavana, Ramila Joshi, James Buchanan, Hossein Tavana, Ramila Joshi, James Buchanan, Hossein Tavana
Controlling cellular microenvironment to induce neural differentiation of embryonic stem cells (ESCs) remains a major challenge. We address this need by introducing a micro-engineered co-culture system that resembles embryonic development in terms of direct intercellular interactions and induces neural differentiation of ESCs. A polymeric aqueous two-phase system (ATPS)-mediated robotic microprinting technology allows precise localization of mouse ESCs (mESCs) over a layer of supporting stromal cells. mESCs proliferate over a 2-week culture period into a single colony of defined size...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#4
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28221817/neuroprotective-effect-of-omega-3-polyunsaturated-fatty-acids-in-the-6-ohda-model-of-parkinson-s-disease-is-mediated-by-a-reduction-of-inducible-nitric-oxide-synthase
#5
Marco Aurélio Mori, Ana Marcia Delattre, Bruno Carabelli, Claudia Pudell, Mariza Bortolanza, Pedro Vinícius Staziaki, Jesuí Vergilio Visentainer, Paula Fernandes Montanher, Elaine A Del Bel, Anete Curte Ferraz
OBJECTIVE: Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons...
February 21, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28220999/the-drosophila-divalent-metal-ion-transporter-malvolio-is-required-in-dopaminergic-neurons-for-feeding-decisions
#6
Eirik Søvik, Angela LaMora, Gurpreet Seehra, Andrew B Barron, Jennifer G Duncan, Yehuda Ben-Shahar
Members of the Natural resistance-associated macrophage protein (NRAMP) family are evolutionarily-conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive...
February 21, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28219741/regulation-of-human-gdnf-gene-expression-in-nigral-dopaminergic-neurons-using-a-new-doxycycline-regulated-nts-polyplex-nanoparticle-system
#7
Armando J Espadas-Alvarez, Michael J Bannon, Carlos E Orozco-Barrios, Lourdes Escobedo-Sanchez, Jose Ayala-Davila, David Reyes-Corona, Guadalupe Soto-Rodriguez, Vicente Escamilla-Rivera, Andrea De Vizcaya-Ruiz, M Eugenia Gutierrez-Castillo, America Padilla-Viveros, Daniel Martinez-Fong
The human glial-cell derived neurotrophic factor (hGDNF) gene transfer by neurotensin (NTS)-polyplex nanoparticles functionally restores the dopamine nigrostriatal system in experimental Parkinson's disease models. However, high levels of sustained expression of GDNF eventually can cause harmful effects. Herein, we report an improved NTS-polyplex nanoparticle system that enables regulation of hGDNF expression within dopaminergic neurons. We constructed NTS-polyplex nanoparticles containing a single bifunctional plasmid that codes for the reverse tetracycline-controlled transactivator advanced (rtTA-Adv) under the control of NBRE3x promoter, and for hGDNF under the control of tetracycline-response element (TRE)...
February 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28219675/tcf7l2-plays-crucial-roles-in-forebrain-development-through-regulation-of-thalamic-and-habenular-neuron-identity-and-connectivity
#8
Myungsin Lee, Jiyeon Yoon, Hobeom Song, Bumwhee Lee, Lam Tri Duc, Jaeseung Yoon, Kwanghee Baek, Hans Clevers, Yongsu Jeong
The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear...
February 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28216145/a-human-neural-crest-stem-cell-derived-dopaminergic-neuronal-model-recapitulates-biochemical-abnormalities-in-gba1-mutation-carriers
#9
Shi-Yu Yang, Michelle Beavan, Kai-Yin Chau, Jan-Willem Taanman, Anthony H V Schapira
Numerically the most important risk factor for the development of Parkinson's disease (PD) is the presence of mutations in the glucocerebrosidase GBA1 gene. In vitro and in vivo studies show that GBA1 mutations reduce glucocerebrosidase (GCase) activity and are associated with increased α-synuclein levels, reflecting similar changes seen in idiopathic PD brain. We have developed a neural crest stem cell-derived dopaminergic neuronal model that recapitulates biochemical abnormalities in GBA1 mutation-associated PD...
February 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215578/mfn2-protects-dopaminergic-neurons-exposed-to-paraquat-both-in-vitro-and-in-vivo-implications-for-idiopathic-parkinson-s-disease
#10
Fanpeng Zhao, Wenzhang Wang, Chunyu Wang, Sandra L Siedlak, Hisashi Fujioka, Beisha Tang, Xiongwei Zhu
Mitochondrial dynamics and quality control plays a critical role in the maintenance of mitochondrial homeostasis and function. Pathogenic mutations of many genes associated with familial Parkinson's disease (PD) caused abnormal mitochondrial dynamics, suggesting a likely involvement of disturbed mitochondrial fission/fusion in the pathogenesis of PD. In this study, we focused on the potential role of mitochondrial fission/fusion in idiopathic PD patients and in neuronal cells and animals exposed to paraquat (PQ), a commonly used herbicide and PD-related neurotoxin, as models for idiopathic PD...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214539/lumbee-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#11
Aurélie de Rus Jacquet, Michael Timmers, Sin Ying Ma, Andrew Thieme, George P McCabe, Jay Hansford C Vest, Mary Ann Lila, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD...
February 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#12
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212942/activation-of-type-4-dopaminergic-receptors-in-the-prelimbic-area-of-medial-prefrontal-cortex-is-necessary-for-the-expression-of-innate-fear-behavior
#13
Macarena D Vergara, Victor N Keller, José A Fuentealba, Katia Gysling
The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212331/analysis-of-epidermal-growth-factor-receptor-related-gene-expression-changes-in-a-cellular-and-animal-model-of-parkinson-s-disease
#14
In-Su Kim, Sushruta Koppula, Shin-Young Park, Dong-Kug Choi
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson's disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP⁺) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP⁺-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP⁺ toxicity. Therefore the pathways that were significantly perturbed in MPP⁺ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h)...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28210976/regenerative-medicine-for-parkinson-s-disease-using-differentiated-nerve-cells-derived-from-human-buccal-fat-pad-stem-cells
#15
Haruka Takahashi, Hiroshi Ishikawa, Akira Tanaka
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks...
February 16, 2017: Human Cell
https://www.readbyqxmd.com/read/28208711/antidepressant-effects-of-aripiprazole-augmentation-for-cilostazol-treated-mice-exposed-to-chronic-mild-stress-after-ischemic-stroke
#16
Yu Ri Kim, Ha Neui Kim, Ki Whan Hong, Hwa Kyoung Shin, Byung Tae Choi
The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208679/vanillin-protects-dopaminergic-neurons-against-inflammation-mediated-cell-death-by-inhibiting-erk1-2-p38-and-the-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Xuan Yan, Dian-Feng Liu, Xiang-Yang Zhang, Dong Liu, Shi-Yao Xu, Guang-Xin Chen, Bing-Xu Huang, Wen-Zhi Ren, Wei Wang, Shou-Peng Fu, Ju-Xiong Liu
Neuroinflammation plays a very important role in the pathogenesis of Parkinson's disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28204862/effect-of-constant-predictable-and-unpredictable-motor-tasks-on-motor-performance-and-blood-markers-of-stress
#18
Laura Kyguoliene, Albertas Skurvydas, Nerijus Eimantas, Neringa Baranauskienė, Dalia Mickeviciene, Daiva Urboniene, Margarita Cernych, Marius Brazaitis
An unfamiliar or novel physical stimulus induces activation of dopaminergic neurons within the brain and greater activity in areas involved in emotion; considering this, we aimed to establish whether unpredictable prolonged (fatiguing) motor task (vs. constant vs. predictable) evokes greater dopaminergic activity, enhances neuromuscular performance, motor accuracy, and perception of effort, and delays overall central fatigue. Fifteen healthy male volunteers (aged 22 ± 4 years) were required to perform 1 of 3 exercise trials (at least 1 week apart) of 100 intermittent isometric contraction (IIC) tasks involving knee extensions at 60° flexion...
February 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28203480/a-novel-immunosuppressor-5r-5-hydroxytriptolide-alleviates-movement-disorder-and-neuroinflammation-in-a-6-ohda-hemiparkinsonian-rat-model
#19
Ruijun Su, Min Sun, Wei Wang, Jianliang Zhang, Li Zhang, Junli Zhen, Yanjing Qian, Yan Zheng, Xiaomin Wang
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Promising therapies for PD still need to be explored. Immune dysfunction has been found to be involved in PD pathogenesis. Here, a novel immunosuppressor, (5R)-5-hydroxytriptolide (LLDT8), was used to treat 6-hydroxydopamine (6-OHDA)-induced hemiparkinson rats. We found that oral administration of LLDT8 significantly alleviated apomorphine-induced rotations at a dose of 125 µg/kg, and improved performance in cylinder and rotarod tests at a lower dose of 31...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28203148/dopamine-d1-receptor-immunoreactivity-on-fine-processes-of-gfap-positive-astrocytes-in-the-substantia-nigra-pars-reticulata-of-adult-mouse
#20
Katsuhiro Nagatomo, Sechiko Suga, Masato Saitoh, Masahito Kogawa, Kazuto Kobayashi, Yoshio Yamamoto, Katsuya Yamada
Substantia nigra pars reticulata (SNr), the major output nucleus of the basal ganglia, receives dopamine from dendrites extending from dopaminergic neurons of the adjacent nucleus pars compacta (SNc), which is known for its selective degeneration in Parkinson's disease. As a recipient for dendritically released dopamine, the dopamine D1 receptor (D1R) is a primary candidate due to its very dense immunoreactivity in the SNr. However, the precise location of D1R remains unclear at the cellular level in the SNr except for that reported on axons/axon terminals of presumably striatal GABAergic neurons...
2017: Frontiers in Neuroanatomy
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