Search

Diabetes induces early sufferance in the cholinergic septo-hippocampal system, characterized by deficits in learning and memory, reduced hippocampal plasticity and abnormal pro-nerve growth factor (proNGF) release from hippocampal cells, all linked to dysfunctions in the muscarinic cholinergic modulation of hippocampal physiology. These alterations are associated with dysregulation of several cholinergic markers, such as the NGF receptor system and the acetylcholine biosynthetic enzyme choline-acetyl transferase (ChAT), in the medial septum and its target, the hippocampus. Controlled and repeated sensory stimulation by electroacupuncture has been proven effective in counteracting the consequences of diabetes on cholinergic system physiology in the brain. Here, we used a well-established Type 1 diabetes model, obtained by injecting young adult male rats with streptozotocin, to induce sufferance in the septo-hippocampal system. We then evaluated the effects of a 3-week treatment with low-frequency electroacupuncture on: (a) the expression and protein distribution of proNGF in the hippocampus, (b) the tissue distribution and content of NGF receptors in the medial septum, (c) the neuronal cholinergic and glial phenotype in the septo-hippocampal circuitry. Twice-a-week treatment with low-frequency electroacupuncture normalized, in both hippocampus and medial septum, the ratio between the neurotrophic NGF and its neurotoxic counterpart, the precursor proNGF. Electroacupuncture regulated the balance between the two major proNGF variants (proNGF-A and proNGF-B) at both gene expression and protein synthesis levels. In addition, electroacupuncture recovered to basal level the pro-neurotrophic NGF receptor tropomyosin receptor kinase-A content, down-regulated in medial septum cholinergic neurons by diabetes. Electroacupuncture also regulated ChAT content in medial septum neurons and its anterograde transport toward the hippocampus. Our data indicate that repeated sensory stimulation can positively affect brain circuits involved in learning and memory, reverting early impairment induced by diabetes development. Electroacupuncture could exert its effects on the septo-hippocampal cholinergic neurotransmission in diabetic rats, not only by rescuing the hippocampal muscarinic responsivity, as previously described, but also normalizing acetylcholine biosynthesis and NGF metabolism in the hippocampus., (© 2019 Wiley Periodicals, Inc.)

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by white matter (WM) changes in different supra- and infratentorial brain structures. We used track density imaging (TDI) to characterize WM microstructural alterations in patients with PSP-Richardson's Syndrome (PSP-RS). Moreover, we investigated the diagnostic utility of TDI in distinguishing patients with PSP-RS from those with Parkinson's disease and healthy controls (HC). Twenty PSP-RS patients, 21 PD patients, and 23 HC underwent a 3 T MRI diffusion-weighted (DW) imaging. Then, we combined constrained spherical deconvolution and WM probabilistic tractography to reconstruct track density maps by calculating the number of WM streamlines traversing each voxel. Voxel-wise analysis was performed to assess group differences in track density maps. A support vector machine (SVM) approach was also used to evaluate the performance of TDI for discriminating between groups. Relative to PD patients, decreases in track density in PSP-RS patients were found in brainstem, cerebellum, thalamus, corpus callosum, and corticospinal tract. Similar findings were obtained between PSP-RS patients and HC. No differences in TDI were observed between PD and HC. SVM approach based on whole-brain analysis differentiated PD patients from PSP-RS with an area under the curve (AUC) of 0.82. The AUC reached a value of 0.98 considering only the voxels belonging to the superior cerebellar peduncle. This study shows that TDI may represent a useful approach for characterizing WM alterations in PSP-RS patients. Moreover, track density decrease in PSP could be considered a new feature for the differentiation of patients with PSP-RS from those with PD., (© 2018 Wiley Periodicals, Inc.)

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography-based network analysis was performed to assess structural connectivity in cerebello-thalamo-basal ganglia-cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123 I-ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT-SPECT evaluation. In addition, NT-PD patients displayed connectivity alterations in nigro-pallidal and fronto-striatal pathways, compared with both controls and TD-PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT-PD group, rigidity-bradykinesia score correlated with fronto-striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico-basal ganglia circuit of NT-PD patients, but not in TD-PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716-4729, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

This work evaluates the potential in diagnostic application of a new advanced neuroimaging method, which delineates the profile of tissue properties along the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS), by means of diffusion tensor imaging (DTI). Twenty-four ALS patients and twenty-four demographically matched healthy subjects were enrolled in this study. The Automated Fiber Quantification (AFQ), a tool for the automatic reconstruction of white matter tract profiles, based on a deterministic tractography algorithm to automatically identify the CST and quantify its diffusion properties, was used. At a group level, the highest non-overlapping DTI-related differences were detected in the cerebral peduncle, posterior limb of the internal capsule, and primary motor cortex. Fractional anisotropy (FA) decrease and mean diffusivity (MD) and radial diffusivity (RD) increases were detected when comparing ALS patients to controls. The machine learning approach used to assess the clinical utility of this DTI tool revealed that, by combining all DTI metrics measured along tract between the cerebral peduncle and the corona radiata, a mean 5-fold cross validation accuracy of 80% was reached in discriminating ALS from controls. Our study provides a useful new neuroimaging tool to characterize ALS-related neurodegenerative processes by means of CST profile. We demonstrated that specific microstructural changes in the upper part of the brainstem might be considered as a valid biomarker. With further validations this method has the potential to be considered a promising step toward the diagnostic utility of DTI measures in ALS. Hum Brain Mapp 38:727-739, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

For many years after its discovery, hydrogen peroxide (H₂O₂) was viewed as a toxic molecule to human tissues; however, in light of recent findings, it is being recognized as an ubiquitous endogenous molecule of life as its biological role has been better elucidated. Indeed, increasing evidence suggests that H₂O₂ may act as a second messenger with a pro-survival role in several physiological processes. In addition, our group has recently demonstrated neuroprotective effects of H₂O₂ on in vitro and in vivo ischaemic models through a catalase (CAT) enzyme-mediated mechanism. Therefore, the present review summarizes experimental data supporting a neuroprotective potential of H₂O₂ in ischaemic stroke that has been principally achieved by means of pharmacological and genetic strategies that modify either the activity or the expression of the superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT enzymes, which are key regulators of H₂O₂ metabolism. It also critically discusses a translational impact concerning the role played by H₂O₂ in ischaemic stroke. Based on these data, we hope that further research will be done in order to better understand the mechanisms underlying H₂O₂ functions and to promote successful H₂O₂ signalling based therapy in ischaemic stroke., (© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.)