Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model

Saar, Galit; Cheng, Ning; Belluscio, Leonardo; Koretsky, Alan P.

doi:10.1016/j.neuroimage.2015.05.045

Cited by 24 publications

(16 citation statements)

References 57 publications

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“…The uptake of Mn 2+ provides excellent visualization of cytoarchitecture [1]. Given this, MEMRI has many applications, including functional imaging of brain regions involved in specific behaviours [11,12], neuronal tract tracing [13,14,15,16,17,18], and imaging morphological changes through development [19], disease [20,21], or during behavioural paradigms [22,23,24].…”

Section: Introductionmentioning

confidence: 99%

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25-50 mg/kg/day MnCl via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl to use for different study designs.

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Section: Introductionmentioning

confidence: 99%

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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“…Therefore labeling is dependent on neuronal signaling (Kikuta et al, 2015). As a result of this mechanism, MEMRI is a powerful tool to map functionally active circuits that change with behavior, pharmacology, and physiology (Pautler, 2006;Saar et al, 2015;Szulc et al, 2015;Ulyanova et al, 2016). Further, MEMRI can be easily performed in conscious animals by activity-dependent distribution of manganese contrast in awake rats for longitudinal studies as with fMRI but with better resolution, and subsequently ex vivo MRI of the brain.…”

Section: Introductionmentioning

confidence: 99%

Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats

et al. 2017

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Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups.

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“…Using better strategies to delineate volume changes in a layer-specific manner could undoubtedly provide insight into this question. Manganese-enhance MRI (MEMRI) has been shown to provide excellent cytoarchitecture of the OB layers in vivo (Aoki, Wu et al 2004, Chuang, Belluscio et al 2010) and has been used to demonstrate laminar-specific effects during degeneration of the OB (Saar, Cheng et al 2015). Thus, combining single-cell MRI tracking with MEMRI could provide insight into laminar specific migration of new neurons in response to odorant-induced activity.…”

Section: Discussionmentioning

confidence: 99%

“…The following parameters were used: Field of View (FOV) = 1.92 cm × 1.92 cm × 1.92 cm, matrix size 256 × 256 × 256 (75-μm nominal isotropic resolution), 12.5 kHz bandwidth, echo time (TE) = 8 ms, repetition time (TR) = 25 ms, and flip angle = 8°. OB volumes were obtained from manually drawn serial voxel of interest (VOI) that covered the entire OB using the Medical Image Processing, Analysis, and Visualization (MIPAV) program (http://mipav.cit.nih.gov) (Saar, Cheng et al 2015). …”

Section: Methodsmentioning

confidence: 99%

Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth

et al. 2017

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Neural progenitors or neuroblasts are produced by precursor cells in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the olfactory bulbs (OB) throughout life. In the OB, these adult born neurons either die or replace existing olfactory interneurons, playing a critical role in the stabilization of OB circuitry. Although several aspects of the addition of new neurons into the OB have been studied, it is unclear whether long-distance activity from the OB can regulate the influx of migrating neuroblasts along the RMS. In this study, iron oxide-assisted MRI was used to track the migration of neuroblasts in combination with reversible naris occlusion to manipulate odorant-induced activity. It was found that decreasing olfactory activity led to a decrease in the rate of neuroblast migration along the RMS. Removal of the naris occlusion led to an increase in migratory rate back to control levels, indicating that olfactory activity has regulatory function on neuroblast migration in the RMS. Blocking odorant activity also led to an arrest in OB growth and re-opening the block led to a rapid re-growth returning the bulb size to control levels. Furthermore, pharmacogenetic elimination of the neuroblasts demonstrated that they were required for re-growth of the bulb following sensory deprivation. Together, these results show that sensory activity, neural migration and OB growth are tightly coupled in an interdependent manner.

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Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model

Cited by 24 publications

References 57 publications

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats

Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth

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