Deep Brain Magnetic Stimulation Promotes Neurogenesis and Restores Cholinergic Activity in a Transgenic Mouse Model of Alzheimer’s Disease

Zhen, Junli; Qian, Yafang; Fu, Junfen; Su, Ruijun; An, Haiting; Wang, Wei; Zheng, Yi; Wang, Xiaomin

doi:10.3389/fncir.2017.00048

Cited by 31 publications

(21 citation statements)

References 29 publications

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“…The 5XFAD model allows for an accelerated timetable of cognitive dysfunction associated with Aβ-related AD pathology in comparison to the Tg2576 model [34,35] which was used in our prior studies. 5XFAD mice show impaired remote memory stabilization prior to four months of age [49]; impaired spatial memory in the Y-maze at 4-5 months of age [35], Morris water maze at six months of age [50,51], and radial water maze at eight months of age [52]; decreased working memory and learning during NORT testing at six months of age [50]; and decreased contextual fear memory by six months of age [38,49,53]. We tested object recall (NORT) and contextual fear (CFR) memory of approximately 8-9 month old female and male 5XFAD mice and WT littermates treated with CAW for 3-4 weeks.…”

Section: Discussionmentioning

confidence: 99%

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

et al. 2019

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Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/ − 0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition.

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Section: Discussionmentioning

confidence: 99%

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

et al. 2019

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“…A recent study showed that hCRY2 senses magnetic field ( 8 ). Magnetic field can be manipulated in clinical practice through transcranial magnetic stimulation, which interestingly increases neurogenesis ( 38 ). Perhaps transcranial magnetic stimulation improves neurologic outcome in a series of neuropsychiatric diseases through stimulation of hCRY expression and consequent neurogenesis.…”

Section: Potential Implications Of the Hypothesismentioning

confidence: 99%

Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome

Nogueira

Veiga

et al. 2017

Front. Neurol.

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We have recently found that the temperature variability (TV) in the day–night cycle may predict the mean intracranial pressure in the following 24 h (ICP24) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP24 = 6 (4 − TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep–wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP24, and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise, visual stimulus with flashing light improves Alzheimer’s disease features in experimental model and there is a prominent expression of CRYs in the retina. Remarkably, recent evidence showed that hCRY2 responds to electromagnetic fields, which could be one elusive mechanism of action of transcranial magnetic stimulation and a reason for its use in SAH.

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“…More recently, biophysical factors have been suggested to induce neurogenesis. Those include ultrasound, magnetic, and deep brain electrical stimulation [25][26][27][28][29][30][31][32][33]. Ultrasound stimulation is non-invasive and can induce hippocampal neurogenesis in healthy mice [29].…”

Section: Introductionmentioning

confidence: 99%

Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

et al. 2020

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Background: Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer's disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer's disease (5xFAD). Methods and results: We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls. Conclusion: Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.

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Deep Brain Magnetic Stimulation Promotes Neurogenesis and Restores Cholinergic Activity in a Transgenic Mouse Model of Alzheimer’s Disease

Cited by 31 publications

References 29 publications

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome

Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

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