|Manganese in the Brain: Methods to Applications|
Seasonal Plasticity of the Olfactory Circuit in
Songbirds Assessed with in-Vivo Manganese Enhanced (MEMRI)
Geert De Groof1, Silke Steiger2, Helga Gwinner2, Annemie Van der Linden1
1University of Antwerp, Antwerp, Belgium; 2Max Planck Institute for Ornithology, Seewiesen, Germany
It is generally believed that birds lack a well-developed sense of smell. Yet there is evidence that some songbirds are able to detect odors. Moreover, it has been shown that starlings show seasonal differences in their ability to respond to odor cues, corresponding to their annual breeding pattern. In starlings, odor sensitivity peaks during nest-building in the spring. This study uses repeated in vivo MEMRI to quantify seasonal changes in the anatomy and activity of the olfactory bulb in starling brains. Seasonal plasticity in the avian brain has already been shown with respect to song nuclei.
Functional Mapping of the Auditory Pathway in Adult
Mice by Manganese-Enhanced MRI
Takashi Watanabe1, Jens Frahm1, Thomas Michaelis1
1Max Planck Institute for Biophysical Chemistry, Goettingen, Germany
This work demonstrates for the first time manganese-enhanced MRI (3D FLASH, 117 µm isotropic resolution) of the lateral lemniscus and the superior olivary complex in adult mice in vivo. These auditory centers in the brainstem presented with pronounced signal enhancements after systemic administration of manganese chloride when animals were exposed to acoustic stimuli for 48 hours, but not when kept in a quiet chamber. The results suggest an activation-dependent accumulation of manganese in the neural circuit connecting the cochlear nucleus via the superior olivary complex and the lateral lemniscus to the inferior colliculus.
In Vivo Tracing Anatomical
Circuitry of the Brains Using Gadolinium
Carolyn Wan-hsun Wu1, Rebecca Ebitz, Haitao Wu2, Gary Griffiths2, Roger Tootell, Alan P. Koretsky1, Leslei G. Ungerleider
1NIH, Bethesda, Maryland, USA; 2NIH, Rockville, Maryland, USA
A shortcoming of conventional neuroanaomy approaches to study neuronal circuitry is that it requires visualizing transported tracer in the post-mortem, histologically processed tissue. The goal of the study is to expand the MRI contrast media available for in vivo neuronal track tracing. In the present study, we show that Gd-DOTA can be used as a MRI visible track tracing agent that reveals anatomical connections in the monosynaptic, anterograde fashion, with results comparable to conventional anatomical tracer. This finding expands the usefulness of Gd-DOTA for longitudinally anatomical studies, especially to study brain wiring during different developmental stages and rewiring following injuries.
Use of Short Chain Oligo-Glycerolipids to Improve BBB
Permeability: Application to Managanese-Enhanced MRI (MEMRI)
Alessandro Gozzi1, Adam Schwarz1, Valerio Crestan1, Livia Ferrari1, Peter Hoffmann2, Matthew Roe3, Angelo Bifone1
1GlaxosmithKline Medicine Research Centre, Verona, Italy; 2Genzyme Pharmaceuticals, Cambridge, USA; 3Genzyme Pharmaceuticals, Haverhill, UK
MEMRI methods can be applied to elucidate neuroanatomical information and to identify regions of increased synaptic activity. However the successful application of MEMRI is often limited by the poor permeability of the BBB to Mn2+ ions. Here we investigated whether administration of short chain oligoglycerolipids can enhance the BBB permeability to Mn2+. Our results show robust and homogeneous bi-hemispheric MEMRI signal enhancements following co-administration of oligo-glycerolipids and MnCl2 through carotid artery. These findings corroborate the exploitation of oligo-glycerolipids as a means to achieve high parenchymal concentration of Mn2+ in the brain.
Overexpression of SOD-2 Reduces Aβ Levels and
Improves the Axonal Transport Deficits in the Tg2576 Alzheimer Model
Cynthia A. Massaad1, Brandon J. Breitling1, Eric Klann2, Robia G. Pautler1
1Baylor College of Medicine, Houston, Texas, USA; 2New York University, New York, New York, USA
In the present study, we show that overexpression of the mitochondrial superoxide dismutase in the Tg2576 alzheimer mouse model, prior to the onset of oxidative stress, reduces the levels of soluble and insoluble Aβ 1-40 and Aβ 1-42 and improves the axonal transport deficits characteristic of the Tg2576 mice. These studies, combined with previous findings from our lab, support the notion that mitochondrial reactive oxygen species are upstream of Aβ pathology in the course of Alzheimerâ€™s disease.
Longitudinal Studies of Neonatal Cerebellum
Phenotypes Development in Gbx2-CKO Mutant Mice Using MEMRI
Kamila Urszula Szulc1, 2, Brian J. Nieman1, Roy V. Sillitoe2, Y Z. Wadghiri1, A L. Joyner2, D H. Turnbull1
1NYU School of Medicine, New York, New York, USA; 2Sloan-Kettering Institute, New York, New York, USA
The cerebellum is a critical brain structure involved in coordination and movement control, and there is growing evidence for additional roles in sensory processing. We previously showed that in vivo manganese-enhanced MRI (MEMRI) can be used to detect midline cerebellum defects in Gbx2 conditional knockout (Gbx2-CKO) mice at postnatal day P11 . Gbx2-CKO mice have variable deletion of vermis, the central cerebellum, which motivates the need for longitudinal imaging to understand the temporal evolution of the mutant phenotypes. We therefore performed longitudinal MEMERI studies of Gbx2-CKO mutant and wild type littermates between P3 and P11, performing volumetric analyses of the cerebellum phenotypes in these mice.
Excitotoxic and Physiological
Stimulations Provide Similar Signal Enhancement on Manganese-Enhanced
Oliviero Gobbo1, 2, Hirac Gurden1, 3, Marc Dhenain1
1CEA, DSV, I2BM, Orsay, France; 2Trinity College, Dublin, Ireland; 3CNRS, Orsay, France
Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) is used to monitor manganese influx into neurons in reaction to functional, physiological, activations. It might thus be used to study functional alterations in animal models of neurodegenerative diseases. However, to date, it is not clear whether excitotoxic events can also modify the MEMRI signal. Here, we showed that, in the olfactory bulb of rats, excitotoxic lesions and odor-evoked physiological activation produce similar MEMRI signal changes. MEMRI studies should thus be conducted with caution in models of neurodegenerative diseases because reduced MEMRI effects caused by functional alterations can be compensated by excitotoxic-related MEMRI enhancement.
Temporal Changes in the T1 and T2 Relaxation Rates
(δR1 and δR2) in the Rat Brain Are Consistent with the Tissue-Clearance
Rates of Elemental Manganese
Kai-Hsiang Chuang1, Alan P. Koretsky1, Christopher H. Sotak
1NINDS, NIH, Bethesda, Maryland, USA
Temporal changes in the T1 and T2 relaxation rates in rat olfactory bulb and cortex before and after i.v. infusion of MnCl2 were compared with the absolute Mn concentrations from the corresponding excised tissue samples. Only a small fraction of the total Mn remained in the brain after 28-35 days. Consequently, the temporal changes in T1 and T2 are mainly due to Mn transport in and out of brain and thus the Manganese-Enhanced MRI signal intensity largely reflects the underlying tissue Mn concentration. This suggests that efflux of cerebral Mn is faster than that reported in earlier studies using other methods.
Detection of Transient Changes in Photothrombotic
Cortical Injury by Manganese-Enhanced Magnetic Resonance Imaging
Kevin C. Chan1, 2, Huan-xing Su1, Ke Xia Cai1, Chi-tat Chiu1, Matthew M. Cheung1, Wu-tian Wu1, Ed Xuekui Wu1
1The University of Hong Kong, Pokfulam, Hong Kong
This study aims to employ in vivo manganese-enhanced MRI to detect transient changes in adult rat model of photothrombotic cortical injury in different brain regions. Results showed a close pattern of MEMRI signal hyperintensity throughout different brain regions in comparison to the distribution of MnSOD and GS immunoreactivities along the time course, whereby conventional MRI could hardly detect such. It is suggested that exogenous Mn2+ injection may provide enhanced MEMRI detection of oxidative stress and gliosis early in the rat model of photothrombotic cortical injury.
Association Between Reduction in Cerebral Blood Flow
and Axonal Transport Deficits in Mouse Models of Diabetes Using MRI
Faridis Serrano1, Tomoya Terashima1, Samir Kamalesh Amin, Lingyun Hu1, Lawrence Chan1, Robia Pautler1
1Baylor College of Medicine, Houston, Texas, USA
A prominent characteristic of the metabolic disease, diabetes mellitus, is hyperglycemia. Hyperglycemia is associated with several complications including vascular disease that most likely contribute to diabetic neuropathy. The aim of this study is to examine the association between alterations in cerebral blood flow (CBF) and axonal transport. We observed that hyperglycemia causes deficits in CBF (assessed with arterial spin labeling) as well as decreases in axonal transport (assessed with Manganese-Enhanced MRI). The possibility to evaluate the impact of hyperglycemia on vascular dysfunction and neuronal physiology in vivo using MRI may be useful in understanding the mechanism of hyperglycemia induced neuropathy.