Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

Pałasz, Artur; Rojczyk, Ewa; Gołyszny, Miłosz; Filipczyk, Łukasz; Worthington, John J.; Wiaderkiewicz, Ryszard

doi:10.1017/neu.2015.56

Cited by 8 publications

(11 citation statements)

References 51 publications

(75 reference statements)

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“…Differences between experimental groups were analyzed using one-way ANOVA followed by Tukey's post hoc test and they were considered significant at p ≤ 0.01 (asterisks) stability in the cells of the brainstem. On the other hand, it is worth emphasizing that chronically administered haloperidol caused a dramatic increase in the expression of neuropeptide S (NPS) mRNA in the brainstem under these conditions [39]. NPS is an endogenous anxiolytic factor, which suggests the effect of haloperidol on anxiety and stress responses in an animal model, which, must be confirmed by further molecular and behavioral studies.…”

Section: Resultsmentioning

confidence: 99%

Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem

et al. 2021

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Background Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug. Methods Studies were carried out on adult, male Sprague–Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression. Results Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged. Conclusions Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.

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Section: Resultsmentioning

confidence: 99%

Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem

et al. 2021

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“…Dense innervation of all major dopaminergic thalamic and hypothalamic cell groups by NPS-immunoreactive fibers was observed in the rat [57] and mouse brain [58]. Furthermore, acute or chronic treatment with both typical and atypical antipsychotic drugs resulted in significant regulation of NPS precursor and NPSR1 transcripts [59,60]. Together, these data suggest important NPS-dopaminergic interactions.…”

Section: Sensitivity To Antipsychotic Treatmentmentioning

confidence: 80%

Neuropeptide S-Mediated Modulation of Prepulse Inhibition Depends on Age, Gender, Stimulus-Timing, and Attention

et al. 2021

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Conflicting reports about the role of neuropeptide S (NPS) in animal models of psychotic-like behavior and inconsistent results from human genetic studies seeking potential associations with schizophrenia prompted us to reevaluate the effects of NPS in the prepulse inhibition (PPI) paradigm in mice. Careful examination of NPS receptor (NPSR1) knockout mice at different ages revealed that PPI deficits are only expressed in young male knockout animals (<12 weeks of age), that can be replicated in NPS precursor knockout mice and appear strain-independent, but are absent in female mice. PPI deficits can be aggravated by MK-801 and alleviated by clozapine. Importantly, treatment of wildtype mice with a centrally-active NPSR1 antagonist was able to mimic PPI deficits. PPI impairment in young male NPSR1 and NPS knockout mice may be caused by attentional deficits that are enhanced by increasing interstimulus intervals. Our data reveal a substantial NPS-dependent developmental influence on PPI performance and confirm a significant role of attentional processes for sensory-motor gating. Through its influence on attention and arousal, NPS appears to positively modulate PPI in young animals, whereas compensatory mechanisms may alleviate NPS-dependent deficits in older mice.

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“…9 B), GNAQ, GRM5, CCK, and NTS. A long-term treatment with haloperidol was found to upregulate the mRNA expression of neuropeptide S receptor (NPSR) in rat brain supporting the involvement of neuropeptide S in the pathophysiology of psychiatric disorders [ 61 ]. Among the network neighbors of dopamine D 2 receptor, ADRA2A (labeled 3 in Fig.…”

Section: Resultsmentioning

confidence: 99%

GraphDTI: A robust deep learning predictor of drug-target interactions from multiple heterogeneous data

Liu

Singha

et al. 2021

J Cheminform

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Traditional techniqueset identification, we developed GraphDTI, a robust machine learning framework integrating the molecular-level information on drugs, proteins, and binding sites with the system-level information on gene expression and protein-protein interactions. In order to properly evaluate the performance of GraphDTI, we compiled a high-quality benchmarking dataset and devised a new cluster-based cross-validation p to identify macromolecular targets for drugs utilize solely the information on a query drug and a putative target. Nonetheless, the mechanisms of action of many drugs depend not only on their binding affinity toward a single protein, but also on the signal transduction through cascades of molecular interactions leading to certain phenotypes. Although using protein-protein interaction networks and drug-perturbed gene expression profiles can facilitate system-level investigations of drug-target interactions, utilizing such large and heterogeneous data poses notable challenges. To improve the state-of-the-art in drug targrotocol. Encouragingly, GraphDTI not only yields an AUC of 0.996 against the validation dataset, but it also generalizes well to unseen data with an AUC of 0.939, significantly outperforming other predictors. Finally, selected examples of identified drug-target interactions are validated against the biomedical literature. Numerous applications of GraphDTI include the investigation of drug polypharmacological effects, side effects through off-target binding, and repositioning opportunities.

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Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

Cited by 8 publications

References 51 publications

Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem

Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem

Neuropeptide S-Mediated Modulation of Prepulse Inhibition Depends on Age, Gender, Stimulus-Timing, and Attention

GraphDTI: A robust deep learning predictor of drug-target interactions from multiple heterogeneous data

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