The effect of chronic neuropeptide-S treatment on non-motor parameters in experimental model of Parkinson’s disease

Sinen, Osman; Bülbül, Mehmet; Derın, Narin; Özkan, Ayşe; Akçay, Güven; Aslan, Mutay; Ağar, Ayşel

doi:10.1080/00207454.2020.1754213

Cited by 13 publications

(12 citation statements)

References 52 publications

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“…The rats were aged eight months at that time-point, suggesting that the age factor was adding to the oligomer toxicity. Interestingly, we found an impaired performance of oligomer-infused rats in the NOR test, indicating some degree of cognitive impairment, and suggesting that the present model deserves further characterization in relation to non-motor symptoms of PD and neuropathologically-related areas [ 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 72%

Modeling Parkinson’s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers

Boi

Pisanu

Palmas

et al. 2020

IJMS

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The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies.

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Section: Discussionmentioning

confidence: 72%

Modeling Parkinson’s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers

Boi

Pisanu

Palmas

et al. 2020

IJMS

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“…The immunohistochemical staining was carried out according to our previously described method (Bulbul et al., 2018; Sinen et al., 2020). Briefly, the brains were fixed by 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

The role of autonomic pathways in peripheral apelin‐induced gastrointestinal dysmotility: involvement of the circumventricular organs

Sinen

Bülbül

2020

Experimental Physiology

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Peripheral administration of apelin-13 has been shown to inhibit gastrointestinal (GI) motility, but the relevant mechanisms are incompletely understood. This study aimed to investigate (i) whether the apelin receptor (APJ) is expressed in circumventricular structures involved in autonomic functions, (ii) whether they are activated by peripherally administered apelin, (iii) the role of autonomic pathways in peripheral exogenous apelin-induced GI dysmotility, and (iv) the changes in apelin levels in the extracellular environment of the brain following its peripheral application. Ninety minutes after apelin-13 administration (300 μg kg −1 , i.p.), gastric emptying (GE) and colon transit (CT) were measured in rats that underwent parasympathectomy and/or sympathectomy. Plasma and cerebrospinal fluid (CSF) samples were also collected from another group of rats that received apelin-13 or vehicle injection. The immunoreactivities for APJ and c-Fos in circumventricular organs (CVOs) were evaluated by immunohistochemistry. Compared with vehicle-treated rats, GE and CT were inhibited significantly by apelin-13 treatment, and were completely restored in animals that underwent the combination of parasympathectomy and sympathectomy and sympathectomy alone, respectively. Apelin concentrations were elevated in both plasma and CSF following peripheral administration of apelin-13. APJ expression was detected in area postrema (AP), subfornical organ and organum vasculosum of lamina terminalis, and c-Fos expression was observed in response to apelin injection. Apelin-induced c-Fos expression in AP was partially attenuated by pretreatment with the cholecystokinin-1 receptor antagonist lorglumide, whereas it was completely abolished in vagotomized rats. The present data suggest that APJ in CVOs could indirectly contribute to the inhibitory action of peripheral apelin on GI motor functions.

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“…The beneficial effects of NPS were also extended to non-motor symptoms of PD. Recently, a study showed that chronic NPS (1 nmol, once a day for 7 consecutive days) administration also alleviates 6-OHDA-induced non-motor behaviors in rats, such as working memory deficits, anxiety and depression-like behaviors [ 13 ], as well as facilitating solid gastric emptying in a parkinsonian animal [ 14 ]. Importantly, expression of NPSR protein was detected in gastro-projecting cells in the dorsal motor nucleus of vagus, thus explaining, in part, the gastric effects of NPS in a PD rat model [ 14 ].…”

Section: Behavioral Effects Of Neuropeptide S: Implications For Parkinson Diseasementioning

confidence: 99%

“…Animal models of PD give further support to the NPS modulatory effects on dopaminergic transmission. For instance, in vivo microdialysis studies showed that acute and 7 days of NPS central administration significantly restored dopamine levels in the substantia nigra [ 11 ] and hippocampus [ 13 ], but not in the striatum [ 13 ], in parkinsonian rats. Therefore, beneficial effects of NPS on PD motor and non-motor dysfunctions may be due to the stimulation of NPSR expressed by dopaminergic neurons in the nigral and mesolimbic pathways.…”

Section: Putative Mechanisms By Which Neuropeptide S Alleviates Parkinson Disease Signs and Symptomsmentioning

confidence: 99%

“…Several in vivo studies replicated these stimulatory actions in rodents (see Table 1 ), and the putative mechanisms were partially described. More recently, studies showing beneficial effects of NPS in counteracting behavioral and neurobiological aspects of PD in rodents have been published [ 11 , 12 , 13 , 14 ]. This review aims to briefly present epidemiological and pathophysiological aspects of PD and to discuss the available pharmacotherapy for this neurodegenerative disease.…”

Section: Introductionmentioning

confidence: 99%

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Neuropeptide S Receptor as an Innovative Therapeutic Target for Parkinson Disease

et al. 2021

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Parkinson disease (PD) is a neurodegenerative disease mainly characterized by the loss of nigral dopaminergic neurons in the substantia nigra pars compacta. Patients suffering from PD develop severe motor dysfunctions and a myriad of non-motor symptoms. The treatment mainly consists of increasing central dopaminergic neurotransmission and alleviating motor symptoms, thus promoting severe side effects without modifying the disease’s progress. A growing body of evidence suggests a close relationship between neuropeptide S (NPS) and its receptor (NPSR) system in PD: (i) double immunofluorescence labeling studies showed that NPSR is expressed in the nigral tyrosine hydroxylase (TH)-positive neurons; (ii) central administration of NPS increases spontaneous locomotion in naïve rodents; (iii) central administration of NPS ameliorates motor and nonmotor dysfunctions in animal models of PD; (iv) microdialysis studies showed that NPS stimulates dopamine release in naïve and parkinsonian rodents; (v) central injection of NPS decreases oxidative damage to proteins and lipids in the rodent brain; and, (vi) 7 days of central administration of NPS protects from the progressive loss of nigral TH-positive cells in parkinsonian rats. Taken together, the NPS/NPSR system seems to be an emerging therapeutic strategy for alleviating motor and non-motor dysfunctions of PD and, possibly, for slowing disease progress.

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The effect of chronic neuropeptide-S treatment on non-motor parameters in experimental model of Parkinson’s disease

Cited by 13 publications

References 52 publications

Modeling Parkinson’s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers

Modeling Parkinson’s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers

The role of autonomic pathways in peripheral apelin‐induced gastrointestinal dysmotility: involvement of the circumventricular organs

Neuropeptide S Receptor as an Innovative Therapeutic Target for Parkinson Disease

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