Papers by Adalberto Merighi
This protocol describes how to perform a Geographic Information Systems (GIS)-based spatial analy... more This protocol describes how to perform a Geographic Information Systems (GIS)-based spatial analysis of cerebellar images. It can be used for any biological images to study cellular or molecular spatial distributions, or, more generally, the distribution of any biological feature of interest. The procedures described here can be employed singularly or in combination to analyze clustering/dispersion by GIS spatially. It is based on the use of ESRI ArcMap to calculate the Average Nearest Neighbor, the High/Low Clustering (G tool), the Multi-distance Spatial Cluster Analysis (Ripley’s K Function), and the Spatial Autocorrelation (Global Moran’s I). It is also shown how to represent the features' distribution graphically.

Italian journal of anatomy and embryology, 2011
Dear colleagues, I never would have imagined that I would be commemorating Vera-in fact, I would ... more Dear colleagues, I never would have imagined that I would be commemorating Vera-in fact, I would have thought the opposite. Unfortunately, fate had other plans. Hence, I am here, commemorating her on behalf of the Group of Veterinary Anatomy of Perugia, which includes Paola Coliolo and Gabriella Mancini. Vera Pedini was born in Perugia on January 18, 1959. She graduated cum laude in Agricultural Science at the University of Perugia in 1980/81, and her supervisor, Professor Fagioli, was a constant presence in her academic career from then on. In fact, he was a member on the commissions of her examinations for both associate professor in 1998, and, subsequently, full professor in 2006. Normally, in a commemoration, one reviews the academic and scientific achievements of the person who has passed. To this end, Vera's notable and highly qualified scientific studies include: mammals major and minor salivary glands, of which she investigated the morphology, ultrastructure (under the initial guidance of Prof. Anna Maria Gargiulo), and histochemical characteristics of secretion, with special reference to the typization of glycoconjugates; the study of fish digestive systems; the identification of endocrine cells in various systems of fish and mammals; and, most recently, stem cells from hair follicles and adipose tissue. However, I believe that the leitmotif of Vera's research can be indentified in the typization of surface glycoconjugates, demonstrated by her prolific activity as an international peer reviewer. Moreover, this topic was at the heart of her relationship with Paola Scocco, which began as a scientific collaboration, but became a solid and sincere friendship. As a teacher, she was very appreciated by colleagues and students alike, at both the undergraduate and postgraduate levels, as well as higher levels of specialization. Nevertheless, I like to remember her as a person and a friend. Vera embodied intelligence, sincerity, irony, cheerfulness, and openness. Her contribution to the scientific, professional, and personal growth of the youngest members of the Group of Veterinary Anatomy of Perugia was essential, as was her contribution to a collaborative and serene work relationship for everyone involved. No less important, though, was her capability to understand academic trends, which made her a valued confidant. Every morning, possibly over a cup of coffee, we would decide what to do in the section, the department, and the faculty. For a long time, and sometimes even now, I tried to imagine how Vera would comment, and, more importantly, how she would have proposed to resolve the delicate and critical steps that involved the small but, and I say this without false modesty, valuable Group of Veterinary Anatomists of Perugia.
Animal models of pain: anatomy, physiology and comparative considerations
F1000Research, 2016
Neuronal depolarization increases bcl-2 expression in post-natal mouse cerebellum
Social Neuroscience, 2005
Modulation of inhibitory post-synaptic currents in spinal lamina II by capsaicin-induced substance P release: a morpho-functional study
Colocalization of BDNF with CGRP and SP in mouse spinal cord dorsal horn
Expression of BCL-2 is not sufficient to rescue progenitor cells from naturally occurring neuronal death in cerebellum
Variations of K+/Ca2+ homeostasis influence BCL-2 expression in postnatal mouse cerebellum
Role of TRPV1 receptors in the modulation of inhibitory neurotransmission in spinal lamina II neurons
Intervention of autophagy in the regulation of cerebellar granule cell survival
Functional and histological evidence for pre-synaptic trkB autoreceptor modulation of glutamate neurotransmission in dorsal horn spinal cord

BMC Neurology, 2017
Background: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologi... more Background: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data. Method: The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized. Results: This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau. Conclusions: Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
Programmed cell death in the postnatal cerebellar development of the Reeler mouse
Annals of Anatomy - Anatomischer Anzeiger, 2016
Microglia-to-neuron communication in spinal nociceptive pathways

Progress in neurobiology, Jan 4, 2018
The substantia gelatinosa Rolandi (SGR) was first described about two centuries ago. In the follo... more The substantia gelatinosa Rolandi (SGR) was first described about two centuries ago. In the following decades an enormous amount of information has permitted us to understand - at least in part - its role in the initial processing of pain and itch. Here, I will first provide a comprehensive picture of the histology, physiology, and neurochemistry of the normal SGR. Then, I will analytically discuss the SGR circuits that have been directly demonstrated or deductively envisaged in the course of the intensive research on this area of the spinal cord, with particular emphasis on the pathways connecting the primary afferent fibers and the intrinsic neurons. The perspective existence of neurochemically-defined sets of primary afferent neurons giving rise to these circuits will be also discussed, with the proposition that a cross-talk between different subsets of peptidergic fibers may be the structural and functional substrate of additional gating mechanisms in SGR. Finally, I highlight t...
Neuromethods, 2015
concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitatio... more concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

Biochemistry and Biophysics Reports
Ex vivo spinal cord slice cultures (SCSC) allow study of spinal cord circuitry, maintaining stimu... more Ex vivo spinal cord slice cultures (SCSC) allow study of spinal cord circuitry, maintaining stimuli responses comparable to live animals. Previously, we have shown that mesenchymal stem/stromal cell (MSC) transplantation in vivo reduced inflammation and increased nerve regeneration but MSC survival was short-lived, highlighting that beneficial action may derive from the secretome. Previous in vitro studies of MSC conditioned medium (CM) have also shown increased neuronal growth. In this study, murine SCSC were cultured in canine MSC CM (harvested from the adipose tissue of excised inguinal fat) and cell phenotypes analysed via immunohistochemistry and confocal microscopy. SCSC in MSC CM displayed enhanced viability after propidium iodide staining. GFAP immunoreactivity was significantly increased in SCSC in MSC CM compared to controls, but with no change in proteoglycan (NG2) immunoreactivity. In contrast, culture in MSC CM significantly decreased the prevalence of βIII-tubulin immunoreactive neurites, whilst Ca 2+ transients per cell were significantly increased. These ex vivo results contradict previous in vitro and in vivo reports of how MSC and their secretome may affect the microenvironment of the spinal cord after injury and highlight the importance of a careful comparison of the different experimental conditions used to assess the potential of cell therapies for the treatment of spinal cord injury.

International Journal of Molecular Sciences
Besides protein processing, the endoplasmic reticulum (ER) has several other functions such as li... more Besides protein processing, the endoplasmic reticulum (ER) has several other functions such as lipid synthesis, the transfer of molecules to other cellular compartments, and the regulation of Ca2+ homeostasis. Before leaving the organelle, proteins must be folded and post-translationally modified. Protein folding and revision require molecular chaperones and a favorable ER environment. When in stressful situations, ER luminal conditions or chaperone capacity are altered, and the cell activates signaling cascades to restore a favorable folding environment triggering the so-called unfolded protein response (UPR) that can lead to autophagy to preserve cell integrity. However, when the UPR is disrupted or insufficient, cell death occurs. This review examines the links between UPR signaling, cell-protective responses, and death following ER stress with a particular focus on those mechanisms that operate in neurons.

F1000Research
Background: Reelin has fundamental functions in the developing and mature brain. Its absence give... more Background: Reelin has fundamental functions in the developing and mature brain. Its absence gives rise to the Reeler phenotype in mice, the first described cerebellar mutation. In homozygous mutants missing the Reelin gene (reln-/-), neurons are incapable of correctly positioning themselves in layered brain areas such as the cerebral and cerebellar cortices. We here demonstrate that by employing ex vivo cultured cerebellar slices one can reduce the number of animals and use a non-recovery procedure to analyze the effects of Reelin on the migration of Purkinje neurons (PNs). Methods: We generated mouse hybrids (L7-GFPrelnF1/) with green fluorescent protein (GFP)-tagged PNs, directly visible under fluorescence microscopy. We then cultured the slices obtained from mice with different reln genotypes and demonstrated that when the slices from reln-/- mutants were co-cultured with those from reln+/- mice, the Reelin produced by the latter induced migration of the PNs to partially rescue ...
Formatio reticularis
Neuroanatomie des Menschen, 2019
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Papers by Adalberto Merighi