Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans

Adult neurogenesis and neurodegenerative diseases: A systems biology perspective

New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research

Visualization of the medial forebrain bundle using diffusion tensor imaging

Diffusion tensor imaging is a technique that enables physicians the portrayal of white matter tracts in vivo. We used this technique in order to depict the medial forebrain bundle (MFB) in 15 consecutive patients between 2012 and 2015. Men and women of all ages were included. There were six women and nine men. The mean age was 58.6 years (39–77). Nine patients were candidates for an eventual deep brain stimulation. Eight of them suffered from Parkinson‘s disease and one had multiple sclerosis. The remaining six patients suffered from different lesions which were situated in the frontal lobe. These were 2 metastasis, 2 meningiomas, 1 cerebral bleeding, and 1 glioblastoma. We used a 3DT1-sequence for the navigation. Furthermore T2- and DTI- sequences were performed. The FOV was 200 × 200 mm2, slice thickness 2 mm, and an acquisition matrix of 96 × 96 yielding nearly isotropic voxels of 2 × 2 × 2 mm. 3-Tesla-MRI was carried out strictly axial using 32 gradient directions and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2. b-value was 800 s/mm2. The maximal angle was 50°. Additional scanning time was < 9 min. We were able to visualize the MFB in 12 of our patients bilaterally and in the remaining three patients we depicted the MFB on one side. It was the contralateral side of the lesion. These were 2 meningiomas and one metastasis. Portrayal of the MFB is possible for everyday routine for neurosurgical interventions. As part of the reward circuitry it might be of substantial importance for neurosurgeons during deep brain stimulation in patients with psychiatric disorders. Surgery in this part of the brain should always take the preservation of this white matter tract into account

Physical exercise-induced adult neurogenesis: A good strategy to prevent cognitive decline in neurodegenerative diseases?

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Modulation of Adult Neurogenesis in the Olfactory Bulb in an Acute Mouse Model of Parkinson´s Disease

Hyposmia, often preceding the cardinal motor symptoms, such as bradykinesia, rigidity, tremor at rest and postural instability, is frequently reported in PD. This symptom appears to be related to an increased number of dopamine neurons in the periglomerular layer (PGL) of the OB. In the histological study, we have investigated the survival and neuronal differentiation of NPC in the OB, following L-DOPA and/or Selegiline in a unilateral, intranigral 6-OHDA lesion model in mice. Our data show that the number of NPC in the SVZ is decreased after 6-OHDA lesion, while there is no difference from control in lesioned mice with Selegiline or L-DOPA treatment. Moreover, the monoamine oxidase-B inhibitor, Selegiline, is able to normalize the number of dopamine neurons by increasing the number of TUNEL+ cell and reverses the dopaminergic differentiation to control in the PGL, while L-DOPA treatment sustains the increased number, by increasing the survival of NPC and upregulating 2-fold dopaminergic differentiation observed in 6-OHDA lesioned animals. In the behavioral study, to understand the olfactory function after 6-OHDA lesion and the effects of Selegiline treatment, six different experimental groups were investigated and performed an olfactory discrimination test. The data show that a delayed olfactory deficit was first appeared 12 weeks post 6-OHDA lesion and the recovery of olfactory function followed a daily, chronic treatment of Selegiline for additional 12 weeks. However, the olfactory dysfunction of the animals relapses again after a 4-week withdrawal of Selegiline treatment. To combine the findings of our studies, we conclude that there is a distinct modulation of newly generated dopamine neurons of the OB after L-DOPA and/or Selegiline treatment. Furthermore, a delayed olfactory deficit was detected after a downregulation of adult neurogenesis, and only a chronic, continuous treatment of Selegiline can reverse the olfactory dysfunction in an acute mouse model of PD. Our findings provide practical implications and stimulate further clinical and preclinical research, bridging the basic knowledge of hyposmia of PD from bench to bedside. Although the relationship of hyposmia and an increased number of dopamine neurons in the OB of PD patients is not well defined yet, the evidence in this study may offer the explanation, that the dysregulation of adult neurogenesis might be one of reasons to cause hyposmia of PD. Moreover, the effects of Selegiline on olfactory function could be a consideration for clinical application. However, further studies are needed to show whether the interaction of dopamine depletion and drug treatment plays a role in olfactory function in PD patients