scholarly journals Altered gastric tone and motility response to brain-stem dopamine in a rat model of parkinsonism

2019 ◽  
Vol 317 (1) ◽  
pp. G1-G7 ◽  
Author(s):  
Cecilia Bove ◽  
Laura Anselmi ◽  
R. Alberto Travagli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Stem ◽  
Gastric Motility ◽  
Rodent Model ◽  
Substantia Nigra Pars Compacta ◽  
Saline Control ◽  
Initial Increase ◽  
Gastric Tone

The majority of patients with Parkinson’s disease (PD) experience gastrointestinal dysfunction. Recently, we described a nigro-vagal pathway that uses dopaminergic (DA) inputs to the dorsal motor nucleus of the vagus (DMV) and A2 area neurons to modulate gastric motility and tone. This pathway is disrupted in a rodent model of PD. The aim of the present study was to test the hypothesis that brain-stem DA modulation of gastric tone and motility is altered in a rodent model of PD. Male Sprague-Dawley rats received three weekly intraperitoneal injections of paraquat (10 mg/kg) or saline (control). In naive conditions, microinjection of DA into the DMV induced a gastroinhibitory response in 100% of animals. In 19 of 28 PQ-treated animals, however, microinjection of DA into the DVC induced a biphasic response, with an initial increase in gastric tone and motility followed by a profound gastroinhibition. The excitatory response to DA microinjection was attenuated by a combination of DA type 1 (DA1)- and DA2-like receptor antagonists. Conversely, the inhibitory response was reduced by the DA2-like receptor antagonist only. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not modulate the response to DA, thus excluding involvement of the A2 area. At the end of the experiments, induction of the Parkinson phenotype was confirmed by the presence of α-synuclein immunoreactivity in the DMV and substantia nigra pars compacta. These data suggest a maladaptive neural plasticity in brain-stem vagal circuits regulating gastric motility in PQ-treated rats that may be responsible for the gastric dysfunction observed in PD models. NEW & NOTEWORTHY After paraquat treatment and induction of Parkinson’s disease, brain-stem dopamine (DA) application induces a biphasic gastric response in the majority of rats, with an initial increase in tone and motility followed by gastroinhibition. The initial increase in gastric tone and motility is mediated via a combined activation of DA type 1 (DA1)- and DA2-like receptors. The inhibitory effects of DA are mediated by DA2-like receptors and are not affected by blockade of adrenergic inputs mediated by α2-adrenoceptors.

scholarly journals Dual Effects of Human Placenta-Derived Neural Cells on Neuroprotection and the Inhibition of Neuroinflammation in a Rodent Model of Parkinson’s Disease

2018 ◽  
Vol 27 (5) ◽  
pp. 814-830 ◽  
Author(s):  
Han Wool Kim ◽  
Hyun-Seob Lee ◽  
Jun Mo Kang ◽  
Sang-Hun Bae ◽  
Chul Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Placenta ◽  
Precursor Cells ◽  
Rodent Model ◽  
Neural Precursor Cells ◽  
Substantia Nigra Pars Compacta ◽  
Neural Precursor ◽  
Age Related ◽  
Therapeutic Mechanisms

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.

Effect of Human Umblical Cord Blood Stem Cells on a Rodent Model of Parkinson's Disease

2018 ◽  
Vol 46 (2) ◽  
pp. 117-127
Author(s):  
Somia Abd-Allah ◽  
El-Sayed Abdel-Aziz ◽  
Sabry Ali ◽  
Gamal El-Din Shams ◽  
Hesham Mohammed ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Cord Blood ◽  
Rodent Model ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells

A PPAR-β/δ Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease

2014 ◽  
Vol 11 (2) ◽  
pp. 114-124 ◽  
Author(s):  
Nihar Das ◽  
Rahul Gangwal ◽  
Mangesh Damre ◽  
Abhay Sangamwar ◽  
Shyam Sharma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Rodent Model

The mechanistic role of thymoquinone in Parkinson's disease: focus on neuroprotection in pre-clinical studies

2021 ◽  
Vol 14 ◽  
Author(s):  
Mohammad Najim Uddin ◽  
Mohammad Injamul Hoq ◽  
Israt Jahan ◽  
Shafayet Ahmed Siddiqui ◽  
Chayan Dhar Clinton ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Studies ◽  
Nigella Sativa ◽  
Biological Effects ◽  
Neuroprotective Activity ◽  
Substantia Nigra Pars Compacta ◽  
Movement Difficulties

: Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.

scholarly journals A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 686
Author(s):  
Simone Agostini ◽  
Roberta Mancuso ◽  
Andrea S. Costa ◽  
Lorenzo A. Citterio ◽  
Franca R. Guerini ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Virus Type ◽  
Humoral Response ◽  
Minor Allele ◽  
Antibody Titers ◽  
Simplex Virus ◽  
System Disorder ◽  
Hsv 1

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

scholarly journals Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

2015 ◽  
Vol 73 (7) ◽  
pp. 616-623 ◽  
Author(s):  
Taysa Bervian Bassani ◽  
Maria A.B.F. Vital ◽  
Laryssa K. Rauh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Inflammatory Process ◽  
Epidemiological Studies ◽  
Substantia Nigra Pars Compacta ◽  
Fine Motor ◽  
Progressive Degeneration ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

Increased gastric motility during 5-HT4 agonist therapy reduces response fluctuations in Parkinson's disease

2005 ◽  
Vol 11 (8) ◽  
pp. 499-502 ◽  
Author(s):  
Hirohide Asai ◽  
Fukashi Udaka ◽  
Makito Hirano ◽  
Takeshi Minami ◽  
Masaya Oda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastric Motility ◽  
Agonist Therapy
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