Biomedical subjects

Marina Bentivoglio

Publications and source records attributed to Marina Bentivoglio.

17 recordsLinked to original sources

PubMed2006

Changes in the expression of P2X1 and P2X2 purinergic receptors in facial motoneurons after nerve lesions in rodents and correlation with motoneuron degeneration.

Involvement of P2X1 and P2X2 purinergic receptors in motoneuron response to injury was investigated with Western blotting and immunohistochemistry and correlated with motoneuron loss, Bcl-2 expression, nitric oxide synthase induction and glial activation. P2X1 was highly induced in rat facial motoneurons after nerve resection, which causes slowly occurring neurodegeneration. P2X1 induction was lower and less persistent after nerve crush, permissive for fiber regeneration. P2X2 expression was found in nuclei of rat facial motoneurons, with nuclear export in the cytoplasm after nerve resection. P2X1 induction in axotomized facial motoneurons was impaired in superoxide dismutase (SOD)1-G93A-mutant mice, a model of motoneuron disease. The data in rats point to a correlation of P2X1 induction with motoneuron degeneration, which also involves P2X2 intracellular changes, rather than with axon regeneration effort. The data in mice show that the SOD1 mutation interferes with injury-elicited P2X1 induction, suggesting alterations of ATP release from mutant motoneurons after damage.

Animals↗

PubMed2006

Suppressors, receptors and effects of cytokines on the aging mouse biological clock.

During aging, levels of inflammatory cytokines increase and circadian rhythms are frequently altered. We here investigated neurobiological correlates of neuroinflammation and its age-related variation in the hypothalamic suprachiasmatic nucleus (SCN), the master circadian pacemaker. Day/night variations of transcripts encoding cytokine receptors and suppressors of cytokine signaling (SOCS) were correlated in groups of mice of different ages with Fos induction elicited by intracerebroventricular injections of tumor necrosis factor-alpha and interferon-gamma. Cytokine-elicited Fos induction was high at early night, when SOCS1 and SOCS3 levels were low. Such Fos induction was significantly reduced in the older SCN at early night, and paralleled by reduced expression of interferon-gamma receptor transcripts as compared to the younger SCN. In addition, Fos induction at early night exhibited marked sub-regional differences in the SCN between the age groups. The study shows that SOCS1 and SOCS3 are expressed in the biological clock with a day/night variation that may regulate SCN responsiveness to cytokine exposure, and indicates that effects of pro-inflammatory cytokines on the SCN are markedly altered during senescence.

Aging↗

PubMed2006

Age-related effects on the biological clock and its behavioral output in a primate.

In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non-human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age-related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free-running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.

Aging↗

PubMed2006

The aging suprachiasmatic nucleus and cytokines: functional, molecular, and cellular changes in rodents.

The aging process brings about a switch to a low-grade chronic inflammatory condition in the periphery and brain, a condition which may prime brain cells, including those of the hypothalamic suprachiasmatic nucleus (SCN). Little information is available, however, on the responses of the SCN to neuroinflammation and immune-related challenges, and such responses have not been hitherto investigated during aging. We here provide an overview of these issues and summarize data we obtained in the study of the SCN of young and aged mice. In particular, we analyzed: i) the electrophysiological properties of the SCN core (the retino-recipient region) in tissue slices; ii) expression and day/night variation of transcripts encoding the receptors for the cytokines interferon-gamma and tumor necrosis factor-alpha, as well as the expression of transcripts encoding the proteins "suppressors of cytokine signaling" SOCS1 and SOCS3, by means of quantitative real-time polymerase chain reaction; levels of mRNAs were correlated with neuronal activation, revealed by Fos induction, elicited in the SCN by intracerebroventricular injections of a mixture of interferon-gamma and tumor necrosis factor-alpha during the daytime and nighttime; and iii) response of astrocytes and microglia in the SCN to the same paradigm of cytokine administration. Marked changes of all the above-mentioned parameters were found in the aged SCN, indicating that the circadian pacemaker is a target of the aging process. In addition, the findings indicate that neurons and glial cells of the biological clock are sensitive to inflammatory signals, and that the response to such signals is altered during senescence.

Aging↗

PubMed2006

Giuseppe Levi: mentor of three Nobel laureates.

Giuseppe Levi (1872-1965), Professor of Anatomy at the University of Turin, had broad research interests and was a pioneer of in vitro studies on cultured cells. He provided a number of contributions on the nervous system, especially on the plasticity of sensory ganglion cells. An influential and magnetic teacher and mentor, he gathered around him a large group of brilliant students. He has the peculiar primate to count among his students three Nobel laureates in Physiology or Medicine: Salvador Luria, Renato Dulbecco, and Rita Levi-Montalcini. For all three of them, the internship in Levi's laboratory provided an exceptional initial stimulus. They remained in close contact with each other and with Levi even after the 1940s when they migrated to the United States for political and racial reasons, engaging in different fields of research. Rita Levi-Montalcini, who was awarded the Nobel Prize (1986) for the discovery of Nerve Growth Factor, was stimulated and assisted in her work by Giuseppe Levi during the difficult years of World War II. With Giuseppe Levi, she pursued early studies on the relationships between neural centers and their peripheral target of innervation, and she has witnessed in her writings the enthusiasm of her mentor.

Anatomy↗

PubMed2005

Arginine-vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging-related alterations of circadian pacemaker neurons in a non-human primate.

The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.

Aging↗

PubMed2004

Nitric oxide synthase expression and cell changes in dorsal root ganglia and spinal dorsal horn of developing and adult Rana esculenta indicate a role of nitric oxide in limb metamorphosis.

Metamorphosis of amphibians requires reconfiguration of sensory and locomotor neural networks. In view of such plastic changes and implications of nitric oxide (NO) in neural developmental shaping, we examined via histochemistry and immunohistochemistry its synthetic enzyme nitric oxide synthase (NOS) in dorsal root ganglia (DRGs) and dorsal horn of the developing and adult frog Rana esculenta. In limb DRGs, NOS positivity was first and selectively detected just before limb bud appearance, increased during metamorphosis, and was then down-regulated. In adulthood, NOS was expressed in some DRG neurons at all segmental levels. Similar features were detected in the dorsal horn neuropil. In limb DRGs, cell counts in Nissl-stained sections revealed a twofold increase of differentiated neurons during metamorphosis and an additional twofold increase in adulthood. Perikaryal sizes in limb DRGs did not vary during metamorphosis but increased and were more heterogeneous in the adult frog, probably reflecting adaptation to body size. NOS and cell changes during metamorphosis were much less marked in DRGs at other levels. Carbocyanine tracing documented selective labeling of NOS-expressing hindlimb DRG neurons from the spinal nerve at the time of initiation of hindlimb movements. The findings show that, in limb DRG neurons, NOS parallels cell differentiation and limb development during metamorphosis. The data also provide evidence of NOS expression in DRG cells innervating the hindlimbs when sensorimotor circuits become functionally mature. This study indicates a key role of NO production in the maturation of sensory functions that subserves in amphibians the transition from swimming to tetrapod locomotion.

Animals↗

PubMed2004

The epithalamus of the developing and adult frog: calretinin expression and habenular asymmetry in Rana esculenta.

Expression of the calcium binding protein (CaBP) calretinin (CR) was studied with immunohistochemistry in the pineal complex and habenular nuclei (HN) of the developing and adult frog Rana esculenta. The frog pineal complex is a medial structure formed by two interconnected components, the frontal organ and the pineal organ or epiphysis; the habenular nuclei are bilateral and are asymmetric due to subdivision of the left dorsal nucleus into medial and lateral components. In the pineal complex, calretinin immunostaining of cells and fibers was consistently observed in developing and adult frogs. In the habenulae, calretinin immunoreactivity exhibited instead marked variations during development, and was expressed only in cells of the medial subnucleus of the left dorsal habenula. In particular, calretinin was detected at larval stages, peaked during metamorphosis, was markedly downregulated at the end of metamorphosis, and was evident again in adulthood. This sequence of calretinin expression was confirmed by quantitative analysis of immunoreactive cells in the left habenula. In tadpoles, calretinin-positive cells exhibited a dorsoventral gradient of density, while in adulthood, they were distributed throughout the dorsoventral extent of the medial subnucleus. The study demonstrates a peculiar developmental pattern, with transient downregulation, of asymmetric calretinin expression in the frog epithalamus. The findings indicate that calcium and calcium buffering systems may play critical roles in neurogenetic and neuronal migration processes implicated in the formation of the asymmetric habenular portion in amphibians. In addition, the reappearance of calretinin expression in the adult frog supports a distinct functional role of the asymmetric habenular component in amphibians.

Animals↗

PubMed2004

Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures.

Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.

Animals↗

PubMed2004

The thalamic paraventricular nucleus relays information from the suprachiasmatic nucleus to the amygdala: a combined anterograde and retrograde tracing study in the rat at the light and electron microscopic levels.

The relationship between efferents of the hypothalamic suprachiasmatic nucleus (SCN) and neurons of the thalamic paraventricular nucleus (PVT) projecting to the amygdala was investigated in the rat using tract tracing in light and electron microscopy. Biotinylated dextran amine was used to label anterogradely SCN efferents. These fibers were found to reach the thalamic midline, terminating in PVT, through three pathways: anterodorsally through the preoptic region, dorsally through the periventricular hypothalamus, and through the contralateral medial hypothalamic and preoptic areas after crossing the midline in the optic chiasm. Preterminal and terminal-like elements labeled from the SCN were distributed throughout the rostrocaudal extent of PVT, with an anteroposterior gradient of density. Labeled terminal elements were densest in the dorsal portion of PVT beneath the ependymal lining and some of them entered the ependyma. Anterograde tracing of SCN fibers was combined with injections of retrograde tracers in the amygdala. Numerous retrogradely labeled cell bodies were seen throughout PVT, with a prevalence in its anterodorsal portion. Overlap was detected between puncta labeled from the SCN and retrogradely labeled neurons, especially in the anterodorsal sector of PVT, where numerous puncta were in close apposition to thalamo-amygdaloid cells. Electron microscopy revealed that boutons labeled from the SCN established synaptic contacts with dendritic profiles of PVT neurons labeled from the amygdala. The findings demonstrate that information processed in the biological clock is conveyed to the amygdala through PVT, indicating that this nucleus plays a role in the transfer of circadian timing information to the limbic system.

Amygdala↗

PubMed2004

Why trypanosomes cause sleeping sickness.

African trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. In contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. This overview discusses that the causative agents, the parasites Trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.

Animals↗

PubMed2003

Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Olfactory cortexes and the olfactory tracts are involved in sporadic Creutzfeldt-Jakob disease. We examined peripheral regions of the olfactory sensory pathway, including the olfactory mucosa, to assess whether pathologic infectious prion protein (PrPSc) is deposited in the epithelium lining the nasal cavity. METHODS: We studied nine patients with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease. We obtained the brain, the cribriform plate with the attached olfactory mucosa, and the surrounding respiratory epithelium at autopsy. Control samples of nasal mucosa were obtained post mortem or at biopsy from age-matched control subjects and from control patients with other neurodegenerative diseases. The olfactory and respiratory mucosa and the intracranial olfactory system were analyzed by light microscopy, immunohistochemistry, and Western blotting for pathological changes and for deposition of PrPSc. RESULTS: In all nine patients with sporadic Creutzfeldt-Jakob disease, PrPSc was found in the olfactory cilia and central olfactory pathway but not in the respiratory mucosa. No PrPSc was detected in any of the tissue samples from the 11 controls. CONCLUSIONS: Our pathological and biochemical studies show that PrPSc is deposited in the neuroepithelium of the olfactory mucosa in patients with sporadic Creutzfeldt-Jakob disease, indicating that olfactory biopsy may provide diagnostic information in living patients. The olfactory pathway may represent a route of infection and a means of spreading prions.

Antibodies, Monoclonal↗

PubMed2003

Musical skills and neural functions. The legacy of the brains of musicians.

An overview of the history of debates on the correlation of musical skills with neurological functions in health and disease is presented. Selected biographical sketches of composers (Hildegard von Bingen, Mozart, Donizetti, Mussorgsky, and Ravel), whose neurological disease may have influenced musical creativity, are discussed. The search for information on the localization of skills in the brains of musicians is reviewed. The relation of mental ability to brain structure is a prominent theme in the history of neuroscience, and the effort to localize musical skills dates back to the excesses of phrenology in the early nineteenth century. The phrenological tables included an "organ of music" among the sites subserving intellectual capabilities, mapped on the basis of palpation of the head bumps. Since the second half of the nineteenth century, when the study of brain physiology, anatomy, and pathology had a remarkable development and impact on the neurosciences, structural features of the brain, particularly the cerebral cortex, of individuals with peculiar talents, including musical skills, have been examined to search for clues on the localization of mental phenomena. These studies, which continued in the twentieth century, are currently difficult to validate in view of the rigor imposed by current scientific standards. However, the issue of localization of functions in the musical brain is still debated and is now at the forefront of the neurosciences, exploiting especially functional neuroimaging. The historical overview of these problems is certainly exemplary of progress of knowledge, but also warns against excessive "localizationist" efforts.

Brain↗

PubMed2003

Cortical development and focal cortical dysplasia.

A brief survey of cortical development is presented, focusing on neuronal migration and its alterations. Corticogenesis is achieved through ordered temporospatial steps, via the formation of transient structures, and successive waves of cell proliferation and migration (followed by cell differentiation and maturation), and apoptotic cell death. The appearance of the proliferative ventricular zone and marginal zone, and of the superficial primordial plexiform layer, is followed by the formation of the prospective layer I, of the subplate, whose neurons are destined to die, and of the cortical plate that will give rise to layers II-VI. Cells arising in the ventricular zone migrate radially using radial glia as a scaffold, and are destined to form pyramidal cells. Cortical interneurons are mainly generated in the ganglionic eminence and migrate along axonal substrates following tangential routes. Disorders of this complex process lead to a wide range of alterations, and focal derangements of cortical organization have been grouped under the term focal cortical dysplasia (FCD). As the result of a neuropathological revision of FCD cases with intractable epilepsy, a novel classification comprising three subgroups of FCD has been introduced, and is supported by electroclinical and neuroimaging data, as well as by the postsurgical outcome of patients: i). architectural dysplasia, characterized by altered cortical lamination; ii). cytoarchitectural dysplasia, with the occurrence of giant neurons besides cortical dyslamination; iii). Taylor-type cortical dysplasia, in which altered cortical lamination is consistently associated with the occurrence of giant, dysmorphic and ectopic neurons, and frequently with the so-called balloon cells.

Cell Movement↗

PubMed2002

Fos induction in cortical interneurons during spontaneous wakefulness of rats in a familiar or enriched environment.

It has been repeatedly reported that Fos is spontaneously induced in several brain structures, including the cerebral cortex, during wakefulness. To ascertain whether cortical interneurons are involved in this state-dependent oscillation of gene regulation, we combined Fos immunocytochemistry with immunostaining of either parvalbumin or calbindin, known markers of cortical interneurons. Immunopositive neurons were examined in the sensorimotor and cingulate cortex. In rats perfused in basal conditions, a minor proportion (around 8%) of Fos-immunoreactive neurons in the parietal cortex were also parvalbumin- or calbindin-immunoreactive; these double immunostained cells accounted for 13% of the parvalbumin- and 34% of the calbindin-labeled neurons. Colocalization of Fos with either calcium-binding protein was instead not observed in the cingulate cortex. In rats stimulated by novel environmental cues during the period of wakefulness preceding perfusion, Fos-positive neurons increased markedly relative to unstimulated animals, and involved the majority of the calbindin- or parvalbumin-labeled cell populations (60-75% and over 95%, respectively). In the neuronal populations in which Fos was induced by exposure to the enriched environment, the proportion of calbindin- and parvalbumin-labeled cells was larger than in the unstimulated cases, and the increment was statistically significant in the cingulate cortex. The results demonstrate that Fos induction occurring in the cortex during undisturbed wakefulness in a familiar environment involves a minor proportion of interneurons. Furthermore, the findings indicate that the addition of novel environmental stimuli results in an increase of Fos-expressing neurons whose recruitment, at least in the cingulate cortex, involves a higher proportion of interneurons than of projection neurons.

Animals↗

PubMed2002

Reaction of mouse brain oligodendrocytes and their precursors, astrocytes and microglia, to proinflammatory mediators circulating in the cerebrospinal fluid.

The response of glial cells to the acute intracerebroventricular administration of interferon-gamma, and of this cytokine combined with the endotoxin lipopolysaccharide or with tumor necrosis factor-alpha, was investigated in the brain of adult mice over a time course of 1 week. Oligodendrocytes were identified by immunocytochemistry, using O4 to label their precursors and 2',3'-cyclic nucleotide 3'-phosphohydrolase as marker of mature cells. Astrocytes were labeled by glial fibrillary acidic protein immunoreactivity and microglial cells by tomato lectin histochemistry. Compared with ovalbumin-injected control cases, all cytokine treatments caused a marked decrease of immunostained mature oligodendrocytes in the brain since 1 day postinjection. O4+ oligodendrocyte precursors increased instead progressively from 2 to 7 days. Astrocytes, markedly activated by cytokine treatments, also exhibited a progressive quantitative increase from 2 days onward. Activation and proliferation of microglial cells were instead most evident at 24 h postinjection. Such glial responses to interferon-gamma injections were especially marked in the periventricular brain parenchyma and were enhanced by coadministration of lipopolysaccharide or tumor necrosis factor-alpha. The findings show that a pulse of proinflammatory mediators in the cerebrospinal fluid affects mature oligodendrocytes, concomitantly with the early appearance of activated microglia, and that such reactions are rapidly followed by an increase of oligodendrocyte precursors paralleled by astrocytic activation. The data, which allowed dissecting the events elicited in glial cell populations by inflammatory mediators via the cerebrospinal fluid, indicate that these molecules elicit in vivo a toxic effect on mature oligodendrocytes and a stimulation of their precursors in the adult brain.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1991

Differential Expression of the GABAA Receptor Complex in the Dorsal Thalamus and Reticular Nucleus: An Immunohistochemical Study in the Adult and Developing Rat.

The distribution of the GABAA receptor/benzodiazepine receptor/chloride channel complex was investigated in the thalamus of the rat by means of immunohistochemistry in adulthood, as well as during embryonic and postnatal development, using a monoclonal antibody. In adults, the immunoreactivity for the GABAA receptor complex was intensely expressed by neuronal processes throughout the dorsal thalamus. Neuronal perikaryal membranes were frequently outlined by punctate immunostaining; cell bodies, intrathalamic fibre bundles and the internal capsule did not display immunoreactivity for the GABAA receptor. Regional differences in the expression of the receptor were consistently observed: the immunostaining was much lighter in the thalamic reticular nucleus than in the dorsal thalamic nuclei and, among the latter, the anteroventral nucleus and the ventral nuclear complex displayed the most intense immunopositivity. Immunostaining for the GABAA receptor was already expressed in embryos at E14, and was homogeneously distributed throughout the neuropil of the dorsal and ventral thalamic primordia. During the first two postnatal weeks, a regional differentiation of the immunopositivity was appreciable in the thalamus, with a progressive reduction in the reticular nucleus and a parallel increase in the dorsal thalamic structures. Immunoreactive neuronal perikarya were not observed in the thalamus at any developmental stage. The expression of the GABAA receptor complex appeared to have reached a mature configuration by the end of the third postnatal week. These findings indicate that in adults the GABAA receptor is differentially expressed by thalamic nuclear structures, including the reticular nucleus. Furthermore, the maturation of the receptor in the thalamus undergoes a rearrangement during the first postnatal weeks that results in a considerable regression within the reticular nucleus.

Journal Article↗