NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice

Rezende, Vítor Bortolo de; Rosa, Daniela V.; Comim, Clarissa M.; Magno, Luiz Alexandre V.; Rodrigues, Ana Lúcia S.; Vidigal, Paula Vieira Teixeira; Jeromin, Andreas; Quevedo, Joao L De; Romano-Silva, Marco Aurélio

doi:10.1016/j.physbeh.2014.03.005

Cited by 30 publications

(36 citation statements)

References 26 publications

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“…However, data from the treadmill equipment suggested otherwise. We therefore concluded that the reduced average speed observed in KO mice may be an example of depressive-like behavior, which has also been described in previous reports [29], because the KO mice often floated with a stiff posture, which resulted in increased escape latency. Thus, our data demonstrate that KO mice exhibit cognitive defects, in accordance with the findings of previous studies that have used a variety of mouse models.…”

Section: Discussionsupporting

confidence: 85%

“…These studies suggest that (1) NCS-1 overexpression in the dentate gyrus promotes synaptic transmission and acquisition of spatial memory [17]; and that (2) NCS-1 knock-down by siRNA or point mutation of NCS-1 harboring a destabilized NCS-1 protein results in deficiencies in exploration and learning function, as assessed using the object recognition test, hole-board test, and new frontier exploration test in mice [28]. Researchers have also reported that NCS-1 KO mice exhibit anxiety and depressive-like behavior, in addition to impaired non-aversive memory [29]. Taken together, these findings strongly reinforce the idea that NCS-1 is a critical regulator of spatial learning and memory function.…”

Section: Discussionmentioning

confidence: 99%

“…Efforts were made to minimize the number of animals used and their suffering. NCS-1 knock-out (KO/ NCS1 -/- ) mice were generated via homologous recombination by Andreas Müllemann and colleagues (2005) from the Université de Genève, and Horst Bluethmann and colleagues from the Hoffmann La-Roche (Switzerland), as previously described [29]. The procedures used to create this mouse strain are available at the MGI database (accession # 3525199).…”

Section: Methodsmentioning

confidence: 99%

“…In mice, overexpression of NCS-1 promotes rapid acquisition of spatial memory [17], whereas downregulation of NCS-1 levels by siRNA causes a deficit in self-directed exploration learning bonus [28]. Furthermore, NCS-1 deficits result in anxiety and depressive-like behavior, as well as impairments in non-aversive memory, in mice [29]. NCS-1 deficiency also decreases motivation-related activity in the nucleus accumbens [30].…”

Section: Introductionmentioning

confidence: 99%

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Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice

et al. 2017

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Intracellular Ca2+ signaling regulates diverse functions of the nervous system. Many of these neuronal functions, including learning and memory, are regulated by neuronal calcium sensor-1 (NCS-1). However, the pathways by which NCS-1 regulates these functions remain poorly understood. Consistent with the findings of previous reports, we revealed that NCS-1 deficient (Ncs1-/-) mice exhibit impaired spatial learning and memory function in the Morris water maze test, although there was little change in their exercise activity, as determined via treadmill-analysis. Expression of brain-derived neurotrophic factor (BDNF; a key regulator of memory function) and dopamine was significantly reduced in the Ncs1-/- mouse brain, without changes in the levels of glial cell-line derived neurotrophic factor or nerve growth factor. Although there were no gross structural abnormalities in the hippocampi of Ncs1-/- mice, electron microscopy analysis revealed that the density of large dense core vesicles in CA1 presynaptic neurons, which release BDNF and dopamine, was decreased. Phosphorylation of Ca2+/calmodulin-dependent protein kinase II-α (CaMKII-α, which is known to trigger long-term potentiation and increase BDNF levels, was significantly reduced in the Ncs1-/- mouse brain. Furthermore, high voltage electric potential stimulation, which increases the levels of BDNF and promotes spatial learning, significantly increased the levels of NCS-1 concomitant with phosphorylated CaMKII-α in the hippocampus; suggesting a close relationship between NCS-1 and CaMKII-α. Our findings indicate that NCS-1 may regulate spatial learning and memory function at least in part through activation of CaMKII-α signaling, which may directly or indirectly increase BDNF production.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice

et al. 2017

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“…Whereas Ncs1 overexpression leads to a dramatic increase in exploration when the homecage is dimly illuminated, a point mutation that destabilises the NCS-1 protein causes a selective decrease in exploration. This work, along with support from others [6] [7], is a prime basis for the notion that NCS-1 plays a key role in the drive to explore novel, safe space. The NFT has also been used to demonstrate selectivity within the amotivation pathophenotype associated with mice following psychosocial stress [8].…”

Section: Introductionmentioning

confidence: 62%