The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia

Choy, Fong Chan; Klarić, Thomas Stephen; Koblar, Simon; Lewis, Martin

doi:10.3390/ijms161226144

Cited by 42 publications

(34 citation statements)

References 118 publications

(202 reference statements)

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“…The observed reduction of the infarct volume was similar to that obtained in mice that were stereotactically injected into the cortex 3 weeks prior to MCAO with rAAVs containing expression cassettes for Npas4 (rAAV-Npas4) (Figures 2A-2D), which has potent neuroprotective activities. 2,5,21,22 It is also comparable to the reduction in stroke volume obtained using rAAV-mediated expression of Activin A. 8 This experiment also revealed that not every AID gene provides effective protection in the MCAO model of acute neurodegeneration.…”

Section: Neuroprotection After Intracerebroventricular Injection Of Rsupporting

confidence: 58%

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

2018

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Synaptic NMDA receptors activating nuclear calcium-driven adaptogenomics control a potent body-own neuroprotective mechanism, referred to as acquired neuroprotection. Viral vector-mediated gene transfer in conjunction with stereotactic surgery has previously demonstrated the proficiency of several nuclear calcium-regulated genes to protect in vivo against brain damage caused by toxic extrasynaptic NMDA receptor signaling following seizures or stroke. Here we used noninvasive nose-to-brain administration of Activin A and SerpinB2, two secreted nuclear calcium-regulated neuroprotectants, for post-injury treatment of brain damage following middle cerebral artery occlusion (MCAO) in C57BL/6N mice. The observed reduction of the infarct volume was comparable to the protection obtained by intracerebroventricular injection of recombinant Activin A or SerpinB2 or by stereotactic delivery 3 weeks prior to the injury of a recombinant adeno-associated virus containing an expression cassette for the potent neuroprotective transcription factor Npas4. These results establish post-injury, nose-to-brain delivery of Activin A and SerpinB2 as effective and possibly clinically applicable treatments of acute and chronic neurodegenerative conditions.

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Section: Neuroprotection After Intracerebroventricular Injection Of Rsupporting

confidence: 58%

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

2018

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“…NPAS4 expression was lower in the cerebellar Purkinje cells of SCA1 mice than those of the WT mice, but this was reversed by treadmill training. Although the regulatory role of NPAS4 in SCA1 remains unclear, the protection of neurons against cerebellar ischemia and neurodegenerative insults in Huntington's disease through upregulated NPAS4 expression were demonstrated. Thus, we suggest that the exercise‐induced increase of cerebellar NPAS4 expression may have reflected the higher neuronal activity in the exercise‐trained SCA1 mice than the nontrained mice.…”

Section: Discussionmentioning

confidence: 99%

Treadmill training increases the motor activity and neuron survival of the cerebellum in a mouse model of spinocerebellar ataxia type 1

Chuang

Chang

Soong

et al. 2019

The Kaohsiung J of Med Scie

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Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1. Therefore, the signal changes and performance of cerebellar neurons after exercise in SCA1 was investigated in this study.We employed a transgenic mouse model of SCA1, generated by amplifying the cytosineadenine-guanine trinucleotide repeat expansions, and the mice underwent 1 month of moderate daily treadmill exercise for 1 hour. The rotarod test revealed that the motor function of the SCA1 mice that underwent training was superior to that of the control SCA1 mice, which did not undergo training. Moreover, the cerebellar pathology revealed preserved Purkinje neurons stained by carbindin with an increase of the neuronal Per Arnt Sim domain protein 4, a key regulation in the structural and functional plasticity of neurons, in the excised SCA1 mice relative to the controls. The mechanism was related to an increase of phosphorylation of ribosomal protein S6, a downstream target of the mammalian target of rapamycin pathway, but not to autophagy activation. This study determined that regular treadmill exercise may play a crucial role in the viable support of cerebellar neurons in SCA1. K E Y W O R D S neuronal Per Arnt Sim domain protein 4, Purkinje neurons, ribosomal protein S6, Spinocerebellar ataxia type 1, treadmill training

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“…It participates in brain's responses to environmental aggression, shaping behavioral and stress responses [6]. Studies have revealed that Npas4 plays a role in stroke through modulation of apoptotic and inflammatory pathways [7]. Differential levels of Npas4 expression in the brain may regulate anxiety, depression and cognition related disorders [8].…”

Section: Introductionmentioning

confidence: 99%

Decreased Npas4 expression in patients with post-stroke depression

Zhao

et al. 2019

Journal of Neurorestoratology

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Purpose:Post-stroke depression (PSD) is a frequent neuropsychiatric disorder following stroke which is associated with poor outcome. Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is associated with cognitive function. Npas4 expression in peripheral blood mononuclear cells (PBMCs) from patients with PSD was measured to find new therapeutic strategy.Patients and methods:Ischemic stroke patients (n = 152) within 1 week of stroke onset were recruited. At 3 months follow-up, the patients were divided into a PSD group (n = 77) and a stroke group (n = 75) using the Hamilton Rating Scale. Healthy subjects (n = 75) were also recruited in the study. The PSD group received 12 weeks of duloxetine treatment. Cognitive function was evaluated using the P300 test. Npas4 expression in PBMCs was measured by quantitative RT-PCR (qPCR).Results:Before treatment, P300 latencies in the PSD group were prolonged and the P300 amplitudes were lower than the control group (P < 0.01). Npas4 expression in the PSD group was also lower than the control group (P < 0.01). After treatment, the P300 latencies were reduced and the amplitudes were significantly elevated in the PSD group compared to that before treatment (P < 0.01). Meanwhile, Npas4 levels were significantly higher than that before treatment (P < 0.01). Npas4 expression was positively correlated to the P300 amplitudes (P < 0.05).Conclusion:Changes of Npas4 expression in PBMCs are associated with cognitive impairment in PSD patients and new therapeutic options applying Npas4-related transcript mechanism could be considered in the future.

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The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia

Cited by 42 publications

References 118 publications

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

Treadmill training increases the motor activity and neuron survival of the cerebellum in a mouse model of spinocerebellar ataxia type 1

Decreased Npas4 expression in patients with post-stroke depression

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