Neuropeptide S Ameliorates Cognitive Impairment of APP/PS1 Transgenic Mice by Promoting Synaptic Plasticity and Reducing Aβ Deposition

Zhao, Peng; Qian, Xiaohang; Nie, Yunjuan; Sun, Na; Wang, Zhongxuan; Chen, Wei; Ma, Ruijuan; Wang, Zhe; Chai, Gaoshang; Li, Yuqing

doi:10.3389/fnbeh.2019.00138

Cited by 27 publications

(15 citation statements)

References 40 publications

(52 reference statements)

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“…The scientific rationale of our study was based on literature findings demonstrating that NPS administration had beneficial effects on learning and memory [ 35 , 37 , 38 , 39 , 40 , 41 ]. However, the effect of NPS administration on cognitive flexibility has not previously been tested.…”

Section: Discussionmentioning

confidence: 99%

“…For example, NPS administration enhances inhibitory avoidance learning [ 35 ], while NPS deficiency reduces inhibitory avoidance learning [ 36 ]. NPS administration has memory-enhancing effects in novel object recognition and Morris water maze [ 37 , 38 , 39 , 40 ] and is able to rescue memory deficits in these and other tests [ 38 , 39 , 41 ]. So far, the question of whether the NPS system is involved in cognitive flexibility has not been addressed.…”

Section: Introductionmentioning

confidence: 99%

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Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

et al. 2021

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Cognitive flexibility refers to the ability to modify learned behavior in response to changes in the environment. In laboratory rodents, cognitive flexibility can be assessed in reversal learning, i.e., the change of contingencies, for example in T-maze discrimination learning. The present study investigated the role of the neuropeptide S (NPS) system in cognitive flexibility. In the first experiment, mice deficient of NPS receptors (NPSR) were tested in T-maze discrimination and reversal learning. In the second experiment, C57BL/6J mice were tested in the T-maze after nasal administration of NPS. Finally, the effect of nasal NPS on locomotor activity was evaluated. NPSR deficiency positively affected the acquisition of T-maze discrimination but had no effects on reversal learning. Nasal NPS administration facilitated reversal learning and supported an allocentric learning strategy without affecting acquisition of the task or locomotor activity. Taken together, the present data show that the NPS system is able to modulate both acquisition of T-maze discrimination and its reversal learning. However, NPSR deficiency only improved discrimination learning, while nasal NPS administration only improved reversal learning, i.e., cognitive flexibility. These effects, which at first glance appear to be contradictory, could be due to the different roles of the NPS system in the brain regions that are important for learning and cognitive flexibility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

et al. 2021

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“…Increased GSK-3 β expression was associated with AD as well. For example, mutations in mice that encodes these genes have resulted in elevated levels of A β deposition, as well as learning and memory impairments ( Myers & McGonigle, 2019 ; Zhao et al, 2019 ). We found that for the first time, piperine does appear to affect the activity of γ -secretase, by decreasing the expression of the catalytic component of the enzyme PSEN1 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Manap

Madhavan

Vijayabalan

et al. 2020

PeerJ

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Previously, we reported the synergistic effects of curcumin and piperine in cell cultures as potential anti-cholinesterase and anti-amyloidogenic agents. Due to limited findings on the enrolment of these compounds on epigenetic events in AD, we aimed at elucidating the expression profiles of Aβ42-induced SH-SY5Y cells using microarray profiling. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and high-throughput microarray profiling was performed on the extracted RNA. This was then compared to curcumin and piperine used singularly at 49.11 µM and 25 µM, respectively. Our results demonstrated that in the curcumin treated group, from the top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ −2), there were five upregulated and three downregulated genes involved in the amyloidogenic pathway. While from top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ − 2) in the piperine treated group, there were four upregulated and three downregulated genes involved in the same pathway, whereas there were five upregulated and two downregulated genes involved (p < 0.05; fold change ≥ 2 or ≤ − 2) in the curcumin-piperine combined group. Four genes namely GABARAPL1, CTSB, RAB5 and AK5 were expressed significantly in all groups. Other genes such as ITPR1, GSK3B, PPP3CC, ERN1, APH1A, CYCS and CALM2 were novel putative genes that are involved in the pathogenesis of AD. We revealed that curcumin and piperine have displayed their actions against Aβ via the modulation of various mechanistic pathways. Alterations in expression profiles of genes in the neuronal cell model may explain Aβ pathology post-treatment and provide new insights for remedial approaches of a combined treatment using curcumin and piperine.

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“…Interestingly, the administration of one such neuropeptide, i.e., Neuropeptide S (NPS) into the APP/PSI mouse model of Alzheimer’s disease (AD), has been shown to result in the reduction of β-Amyloid plaques indicating the clinical relevance of employing neuropeptides in treating age related disorders of the brain ( Zhao et al, 2019 ). Neuropeptide S is also shown to promote olfactory, and spatial memory in rodent models ( Wang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

Bhat

Shahi

Surendran

et al. 2021

Front. Mol. Neurosci.

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One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

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Neuropeptide S Ameliorates Cognitive Impairment of APP/PS1 Transgenic Mice by Promoting Synaptic Plasticity and Reducing Aβ Deposition

Cited by 27 publications

References 40 publications

Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

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