M Santarelli

Università degli Studi di Firenze, Florence, Tuscany, Italy

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Publications (10)22.51 Total impact

  • Article: The organisation of spinal projecting brainstem neurons in an animal model of muscular dystrophy. A retrograde tracing study on mdx mutant mice.
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    ABSTRACT: Previous studies we performed on the mdx mouse demonstrated marked central nervous system alterations in this model of human Duchenne muscular dystrophy, such as reduction in number and pathological changes of cortico-spinal neurons. Prompted by these findings we extended the survey of the mdx brain to the major brainstem-descending pathways: the rubro-, vestibulo-, reticulo-, and raphe-spinal projections. Horseradish peroxidase microinjections were performed in the cervical spinal cord of mdx and control mice. The rubro-spinal neurons were found to be significantly reduced in mutants compared to controls. The vestibulo-spinal, reticulo-spinal, and raphe-spinal cell populations, though less numerous in mdx than in control mice, were instead substantially spared. Our data further unveil the selective nature of mdx brain damage indicating a marked and selective involvement of the highest centers for motor control.
    Brain Research 04/2001; 895(1-2):213-22. · 2.73 Impact Factor
  • Article: A simple pressure microinjecting system for delivery of small substance volumes to the brain: application to the developmental study of thalamo-cortical projections in foetal and neonatal rats.
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    ABSTRACT: We describe a reliable and inexpensive method for placing injections of anatomical tracers into the brain of lower mammals. The pressure microinjecting system we developed is specifically designed to deliver very small amount of substances. The injecting portion of the system is relatively easy to assemble and can be repeatedly used for multiple experimental sessions. The system has been validated with experiments of multiple fluorescent retrograde tracing. In these experiments the populations of thalamo-cortical neurons were consistently labeled by the tracers injected bilaterally and symmetrically in the cortex of foetal and neonatal rats.
    Brain Research Protocols 02/1999; 3(3):257-63. · 1.82 Impact Factor
  • Article: An optimised procedure for prenatal ethanol exposure with determination of its effects on central nervous system connections.
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    ABSTRACT: We describe the protocol set-up to investigate an experimental model of foetal alcohol syndrome in the rat. The protocol has been devised to expose specific cell populations of the central nervous system to ethanol during their neurogenesis and has been applied to the study of diencephalo-telencephalic connections. We were able to demonstrate specific permanent changes of the adult thalamo-cortical circuitry. Our protocol can be applied to study other aspects of central nervous system-ethanol interactions, such as neurotransmitter and receptor patterns. It can also represent a useful tool to test the effects of different diets to prevent nutritional deficiencies and the efficacy of drug treatments to prevent foetal alcohol syndrome. We have shown in fact that ethanol-induced thalamo-cortical alterations are partially prevented by concurrent administration of acetyl-L-carnitine. Finally, the present protocol can be used to investigate the effects of ethanol exposure on the development of different brain structures. To this purpose, the gestational period for ethanol exposure must be chosen according to the peak of neurogenesis for the investigated structure.
    Brain Research Protocols 02/1999; 3(3):264-9. · 1.82 Impact Factor
  • Article: Crossed thalamo-cortical and cortico-thalamic projections in adult mice.
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    ABSTRACT: The crossed thalamo-cortical and cortico-thalamic connections of the mouse are drawn using the tracer wheat germ agglutinin-horseradish peroxidase. After injections in the frontal cortex of the right hemisphere cells labeled retrogradely and axons labeled anterogradely are observed in the thalamus ipsilateral and contralateral to the cortical injections. The retrograde and anterograde labeling in the contralateral thalamus is less intense than ipsilaterally and involves the mediodorsal, ventral medial, central medial, and paracentral nuclei. Crossed fronto-thalamic axons reach more lateral regions than those containing contralateral thalamo-frontal neurons. Our results demonstrate that the thalamo-cortical system of mice has a bilateral component. The functional significance of this pathway and analogies with crossed thalamo-cortical connections in other species are discussed.
    Neuroscience Letters 03/1996; 204(1-2):69-72. · 2.11 Impact Factor
  • Article: Architectural changes of the cortico-spinal system in the dystrophin defective mdx mouse.
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    ABSTRACT: The mutant mdx mice which lack the protein dystrophin are an animal model of Duchenne muscular dystrophy. We studied the organization of the cortico-spinal (CS) system in mdx mice using the horseradish peroxidase retrograde tracing technique. Tracer injections were placed in the cervical spinal cord of mutant and control mice. The tangential and radial distribution of CS labeled neurons were similar in mdx and normal mice. Conversely, the absolute number and the cell packing density of labeled CS neurons were considerably lower in mdx than in controls. In mdx, the average size of CS cells was smaller while the perikaryal sizes displayed a normal distribution. In addition, CS neurons of mdx appeared round-shaped compared to the pyramidal cells labeled in control animals. The structural modifications described here should prompt a reconsideration of the involvement of central nervous system in the dystrophin deficient mdx mice.
    Neuroscience Letters 12/1995; 200(1):53-6. · 2.11 Impact Factor
  • Article: Mapping subcortical extrarelay afferents onto primary somatosensory and visual areas in cats.
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    ABSTRACT: Projections from the claustrum (Cl) and the thalamic anterior intralaminar nuclei (AIN) to different representations within the primary somatosensory (S1) and visual (V1) areas were studied using the multiple retrograde fluorescent tracing technique. The injected cortical regions were identified electrophysiologically. Retrograde labeling in Cl reveals two different projection patterns. The first pattern is characterized by a clear topographic organization and is composed of two parts. The somatosensory Cl shows a dorsoventral progression of cells projecting to the hindpaw, forepaw, and face representations of S1. The visual Cl has cells projecting to the vertical meridian representation of V1 surrounded dorsally by neurons projecting to the representation of retinal periphery. A second pattern of Cl projections is composed of neurons that are distributed diffusely through the nucleus. In both somatosensory and visual sectors, these intermingle with the topographically projecting cells. Neurons retrogradely labeled from cortical injections are always present in the AIN. In the central medial nucleus, the segregation of modality is evident: The visual-projecting sector is dorsal, and the somatosensory is ventral. Projections from the central lateral nucleus display detectable somatotopic and retinotopic organization: Individual regions are preferentially connected with specific representations of S1 or V1. In the paracentral nucleus, no clear regional preferences are detectable. Also performed were comparisons of the proportions of neurons projecting to different sensory representations. Projections to V1 from both AIN and Cl are biased towards the retinal periphery representation. S1 projection preference is for the forepaw representation in Cl and for the hindpaw in the AIN. The quantitative analysis of multiply labeled cells reveals that, compared to Cl, the AIN contains a higher proportion of neurons branching between different representations of S1 or V1. The concept of topographic vs. diffuse projecting systems is reviewed and discussed, and functional implications of quantitative analysis are considered.
    The Journal of Comparative Neurology 12/1995; 362(1):46-70. · 3.81 Impact Factor
  • Article: Multifaceted alterations of the thalamo-cortico-thalamic loop in adult rats prenatally exposed to ethanol.
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    ABSTRACT: The thalamo-cortico-thalamic loop was investigated in adult rats exposed to ethanol during the last week of fetal life. Animals underwent either cortical or thalamic injections of lectin-conjugated horseradish peroxidase. Results demonstrate that prenatal exposure to ethanol causes permanent changes in the thalamocortical circuits. Alterations of thalamo-cortical and cortico-thalamic projections are concentrated at the level of axon terminal fields. The most severe thalamic damage is observed in the anterior intralaminar and midline nuclei; crossed cortico-thalamic projections also appear to be severely impaired. In the cortex, the damage to thalamic terminals displays a medio-lateral gradient of increasing severity through sensori-motor areas, with the lateral fields more impaired. Cells of origin of thalamo-cortical and cortico-thalamic projections are less affected by prenatal ethanol exposure: in the thalamus and layer 5 of sensori-motor cortex labeled cells exhibit normal values of areal numeric density. Conversely, cortico-thalamic neurons of layer 6, especially in the lateral agranular sensori-motor field, display smaller values of areal density than those of normal animals. Possible mechanisms underlying the establishment of these abnormalities are discussed.
    Anatomy and Embryology 02/1995; 191(1):11-23. · 1.42 Impact Factor
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    Article: Alterations of neocortical neuronal responses to acetylcholine and GABA in rats born to alcohol-dependent mothers.
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    ABSTRACT: Alcohol is known to be a CNS teratogenic factor interfering with neuronal and synaptic maturation. The purpose of this microiontophoretic study was to explore GABAergic and cholinergic central mechanisms in adult rats exposed to alcohol in the third phase of prenatal life (ADM), when their mothers were subjected to alcohol physical dependence induction (9.6 g/kg/day). Responses to acetylcholine and GABA were recorded in frontal and somatosensory cortical neurons. Adult rats, whose mothers had been administered placebo with identical procedures, were used as a control (C). Cholinergic responses were significantly decreased and GABAergic responses increased in ADM animals with respect to controls. After a single i.p. alcohol injection (1.6 g/kg) spontaneous firing was depressed in ADM animals to a lesser extent than in C rats. Cholinergic excitations were reduced in C group and potentiated with reversal of atropine antagonism in ADM animals. GABAergic inhibitions were slightly increased and bicuculline antagonism was blocked in C rats, while ADM animals showed decreased responses to GABA. The present results support the hyperactivity of GABAergic system and the hypoactivity of cholinergic system reported in previous studies on prenatally and postnatally alcohol-exposed animals. Microiontophoretic results following ethanol injection led to the hypothesis that a rapid tolerance/dependence may develop in the offspring of alcohol-dependent rats.
    Alcohol and Alcoholism 10/1994; 29(5):611-9. · 2.95 Impact Factor
  • Article: Modifications of thalamo-cortical circuitry in rats prenatally exposed to ethanol.
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    ABSTRACT: The present study aimed to investigate the organization of thalamo-cortical connections in adult rats exposed to ethanol during the last week of foetal life. Animals underwent thalamic injections of lectin-conjugated HRP. Results demonstrate that the thalamic-recipient zone of sensorimotor cortex is significantly thinner in ethanol-exposed than in control cases. Animals exposed to ethanol also display aberrant thalamo-cortical terminations in layer 5a. Neurones of origin of cortico-thalamic projections are normally located in layers 5 and 6; they appear quantitatively comparable in control and ethanol-exposed cases. Developmental alterations underlying the establishment of anomalous thalamo-cortical relationships are discussed.
    Neuroreport 05/1993; 4(4):415-8. · 1.66 Impact Factor
  • Article: Bihemispheric organization of amygdalo-cortical projections in the rat.
    A Granato, M Santarelli, D Minciacchi
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    ABSTRACT: Two fluorescent dyes were injected symmetrically into the prefrontal cortices of the left and right hemisphere. A consistent number of amygdaloid neurons was labeled from the injection in the contralateral cortex. Each nucleus of the basolateral amygdaloid complex showed a specific pattern of contralaterality. The highest degree of bihemisphericity was observed in the ventral basolateral nucleus. A significant number of neurons connected with the cortex of both hemispheres by means of axon collaterals was observed in the anterior basolateral nucleus. These anatomical findings indicate that the basolateral amygdaloid complex could act as subcortical link for interhemispheric communication.
    Neuroscience Letters 07/1991; 127(1):53-6. · 2.11 Impact Factor

Institutions

  • 1996–2001
    • Università degli Studi di Firenze
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florence, Tuscany, Italy
  • 1991–1999
    • The Catholic University of America
      Washington, D. C., DC, USA