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Biomedical subjects

M Bentivoglio

Publications and source records attributed to M Bentivoglio.

At least 73 records · Page 4Linked to original sources

The chemical heterogeneity of cortical interneurons: nitric oxide synthase vs. calbindin and parvalbumin immunoreactivity in the rat.

Neurons that contain nitric oxide synthase (NOS) type I and the calcium binding proteins calbindin D28k or parvalbumin were simultaneously visualized by means of double immunohistofluorescence in the cerebral cortex of Wistar and Sprague-Dawley rats. All the three immunoreactive cell populations were primarily represented by nonpyramidal neurons. NOS-immunoreactive cells were less numerous than the calbindin- or parvalbumin-immunoreactive ones, and were intermingled with the neurons containing these calcium binding proteins. NOS-immunoreactive cells were separate from the parvalbumin-immunoreactive ones, whereas a minor proportion of them was found to be colocalized with calbindin. The cortical neurons in which NOS and calbindin coexisted were more numerous in the Sprague-Dawley than in the Wistar rats, and displayed an anteroposterior gradient of density, with the highest concentration in the medial prefrontal, frontal, and cingulate cortices. Double NOS-calbindin-immunoreactive neurons prevailed in the deep cortical layers and they were relatively numerous in the cingulate cortex. The present data indicate a selectivity in the expression of NOS vs. calbindin and parvalbumin in cortical cells, and further support the chemical heterogeneity of GABAergic interneurons in the cerebral cortex.

Animals↗

Branched connections to the septum and to the entorhinal cortex from the hippocampus, amygdala, and diencephalon in the rat.

Neuronal cell populations giving origin to bifurcating projections to the septum and the entorhinal cortex were studied in the rat by means of double retrograde labeling using the fluorescent tracers Fast Blue and Diamidino Yellow. Double labeled pyramidal neurons were consistently detected in the temporal level of the CA1 area and subiculum of the hippocampal formation, where they represented at least 50% of the cells retrogradely labeled from the entorhinal injections. Double labeled neurons were also detected in the amygdala, where they prevailed in the basal complex. Scattered double labeled neurons were observed in a number of hypothalamic nuclei, with a slight predominance in the preoptic region. Finally, a few double labeled cells were detected in the midline thalamus, and especially in the thalamic paraventricular nucleus. In all these structures, double labeled neurons were located ispilaterally to the injection sites. The present data indicate that the septum and entorhinal cortex are tightly interconnected by axonal bifurcations deriving from a variety of telencephalic and diencephalic sources.

Amygdala↗

1896-1996: the centennial of the axon.

The term "axon" was coined by Koelliker in 1896. To celebrate the occasion of this centennial, the contributions made in the 19th century by Remak and Deiters to the discovery of the structural uniqueness of the axon, and its continuity with the nerve cell body are highlighted briefly, and an overview is provided of the pioneering studies performed in the 18th century. Leeuwenhoek, Dutch pioneer of microscopic investigations, first observed nerve fibers in 1717 and described them as "very minute vessels." Fontana, rigorous and ingenious investigator primarily interested in the biological effects of the viper venom, is credited with the first report of nerve fibers, of which he provided in 1781 a remarkable description as "transparent, uniform and simple cylinders," "primitive organic elements" that can form a nerve.

Animals↗

Twenty-four-hour antihypertensive efficacy of felodipine 10 mg extended-release: the Italian inter-university study.

We assessed the 24-h antihypertensive efficacy of an extended-release (ER) 10-mg formulation of the dihydropyridine felodipine in mild-to-moderate essential hypertension [World Health Organization (WHO) stage I-II]. Thirty patients, 23 men and 7 women, aged 37-70 years (mean 53 +/- 9 years) participated in a double-blind, randomized, cross-over study of felodipine 10 mg ER versus placebo. An ambulatory daytime diastolic blood pressure (DBP) >90 mm Hg at the end of a 4-week run-in period was necessary to enter the 10-week treatment phase. Twenty-nine patients completed the treatment phase. Twenty-two underwent a 2-day single-blind placebo follow-up to assess residual drug effects. All patients underwent ambulatory BP monitoring (ABPM) by Spacelabs 90207 recorders. Recorders were programmed to make automatic BP and heart rate (HR) measurements every 15 min throughout the 24 h. Felodipine 10 mg ER significantly (p < 0.01) reduced ambulatory systolic BP (SBP) and DBP values throughout the 24-h, day (7 a.m. to 11 p.m.) and night (11 p.m. to 7 a.m.) periods, but not influencing average ambulatory HR values. Trough-to-peak (T/P) ratios, calculated on the average ambulatory BP values measured in the 7-9 a.m. 2-h interval of the second day of ABPM (before the new drug administration: trough) and in the 10 a.m. to 12 noon 2-h interval of the first day of ABPM (peak BP-lowering effect), were 0.71 and 0.58 for SBP and DBP, respectively. Individual T/P calculations, after post hoc selection of nonresponders, gave superimposable results, the consistency of which was judged on mean, median, and confidence intervals (CI). However, the wide variability of the individual T/P ratios suggests that this method cannot be the only means to evaluate the duration of action of an antihypertensive drug by ABPM. The long-acting BP-lowering drug effect was clearly shown by the ABPM performed in the follow-up when SBP and DBP average values of the 24-h, day, and night periods were still reduced. Felodipine 10 mg ER effectively reduced BP in patients with mild-to-moderate hypertension, showing prolonged duration of its antihypertensive action beyond the time of the next dose.

Adult↗

Rabies: interactions between neurons and viruses. A review of the history of Negri inclusion bodies.

The first clear-cut description of a virus-nerve cell interaction was made by Adelchi Negri in 1903 with the detection of cytoplasmic bodies (Negri bodies) in subsets of neurons in the brain from rabies-infected animals. A biographical sketch of Negri is given here; he was born in Perugia, Italy, in 1875 and died in Pavia in 1912. In 1900 Negri became assistant to Camillo Golgi, who encouraged him to study rabies-infected brains with histological techniques. The report of intraneuronal bodies described by Negri as specific for rabies stimulated an intense debate both concerning their diagnostic value and their nature. The diagnostic value was finally determined in a study by Negri's wife, Lina Negri-Luzzani, in 1913, while the viral nature of the bodies had to await the introduction of electron microscopy and immunohistochemistry. However, the true significance of the Negri bodies is still mysterious, since they only develop in subsets of infected neurons and occur mainly after infection with wild, so-called 'street', virus strains and not after infection with strains passaged in the laboratory, so-called 'fixed' strains.

Animals↗

Independent efferent populations in the nucleus of the optic tract: an anatomical and physiological study in rat and cat.

The efferent projections of the nucleus of the optic tract (NOT) and dorsal terminal nucleus of the accessory optic system (DTN) to the contralateral NOT-DTN, ipsilateral inferior olive (IO), ipsilateral nucleus prepositus hypoglossi (NPH), and ipsilateral dorsal lateral geniculate nucleus (LGNd) were examined in pigmented rats and in cats by using anterograde and retrograde tract tracing, as well as extracellular recording and electrical stimulation. Anterograde tracing in the rat revealed a dense termination field of NOT-DTN efferents throughout the homologous contralateral territory. In both species three different cell populations, projecting to the contralateral NOT-DTN, ipsilateral IO, and ipsilateral LGNd, respectively, were distinguished by means of multiple retrograde tracing. No clear topographical segregation of the different NOT-DTN relay cell populations was observed. On the other hand, a large proportion (at least 60%) of NOT-DTN neurons projecting to the ipsilateral NPH were found to bifurcate upon the IO in the rat. Electrophysiologically, NOT-DTN neurons projecting to the IO were identified by their directionally selective responses. Such neurons were never activated by electrical stimulation of either the contralateral NOT-DTN or the ipsilateral LGNd. Neurons antidromically activated from the contralateral NOT-DTN could not be activated from the ipsilateral LGNd. Thus, in both cat and rat the NOT-DTN includes at least three independent relay cell populations. As a consequence, the NOT-DTN must serve functions additional to the generation of eye movements during optokinetic nystagnus, a function subserved by the directionally selective NOT-DTN cells.

Animals↗

Suicide retrograde transport of volkensin in cerebellar afferents: direct evidence, neuronal lesions and comparison with ricin.

Volkensin and ricin, either free or conjugated with colloidal gold, were injected into the cerebellar cortex of rats. The inferior olive and pontine nuclei were examined to verify the retrograde axonal transport of these two toxins, and the consequent neuronal damage. No evidence was obtained of a retrograde axonal transport of ricin in these pathways. Injection of gold-conjugated volkensin in the cerebellar cortex resulted in retrogradely labelled neurones in the inferior olive after 3 h, and in the pontine nuclei after 6 h. Degenerative changes were very severe in the retrogradely labelled neurones 48 h after the gold-conjugated volkensin injection. In the Nissl-stained material, neuronal degeneration started to be evident in the inferior olive 12 h, and in pontine nuclei 6 h, after volkensin injection. The neuronal degeneration in both the inferior olive and pons increased up to 4 days after the injection. These findings provide direct evidence of the retrograde axonal transport of volkensin in the central nervous system, and the time course of the consequent degenerative changes in the afferents to the cerebellar cortex.

Animals↗

Fos-related protein expression in the midline paraventricular nucleus of the rat thalamus: basal oscillation and relationship with limbic efferents.

The expression of Fos-related protein, encoded by the proto-oncogene c-fos, was investigated by means of immunohistochemistry in the paraventricular nucleus of the thalamic midline (PV) during nighttime and daytime in rats entrained to a 12-h light/12-h dark cycle. In the first step of this study the animal's physiological state preceding perfusion was monitored with electro-encephalographic recording. It was thus detected that the PV contained a considerable number of Fos-like-immunostained neurons during the hours of darkness, when the rats had been awake, and that the number of Fos-like-immunoreactive neurons was significantly lower during the hours of light, after a period of sleep. In the second step of this study Fos immunohistochemistry was combined with the retrograde transport of a gold-labeled tracer injected either in the amygdala or in the nucleus accumbens. This strategy enabled us to determine that in the rats perfused during nighttime Fos-related protein was spontaneously induced in PV cells projecting to these targets, with a significant prevalence of neurons projecting to the amygdala in the anterior portion of the PV and of neurons projecting to the nucleus accumbens in the posterior part of the nucleus. In addition, a significant reduction of Fos-like-immunoreactive cells was detected in the PV ipsilaterally to the injection, indicating that tracer administration and axonal transport may interfere with c-fos expression in neurons. Altogether the present data indicate that Fos-related protein expression undergoes a marked oscillation in the PV during 24 h in basal conditions, and that c-fos is induced in the PV relay neuronal subsets when the animal is awake.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

The Proustian itinerary from sensation to memory.

Information processing streams that proceed through the sensory unimodal and multimodal areas of the cerebral cortex, and hence the limbic system, bring from perception to memory. This itinerary through the neural networks underlying perception and cognition is briefly outlined through famous passages from Marcel Proust's "Swann's Way", in which the flavour of the "petites madeleines" triggers vivid recollection.

Cognition↗

A sensitive double immunostaining protocol for Fos-immunoreactive neurons.

Immunostaining of Fos, the nuclear protein encoded by the immediate early gene c-fos, is widely used to reveal the functional activation of neurons. The chemical identity of cells that express c-fos can be investigated with double immunohistochemistry. We report the usefulness of a sequential two-color avidin-biotin-immunoperoxidase method that provides a highly sensitive double immunostaining and allows long-term storage of the sections. In this protocol, metal intensification of diaminobenzidine (int-DAB) resulted in dark brown/black Fos immunostaining of the neuronal nucleus. The use of alpha-naphthol/pyronin reaction product yielded pink immunostaining of a second antigen in the cytoplasm. This combination produced higher contrast than that produced by int-DAB Fos immunostaining combined with conventional DAB light brown cytoplasmic staining. The sensitivity of the use of int-DAB and alpha-naphthol/pyronin was verified in different experimental paradigms, combining the immunocytochemical detection of Fos with that of the p75 nerve growth factor receptor, or parvalbumin, or calbindin D28k.

Ammonium Sulfate↗

Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats.

The rest-activity and body temperature 24 h cycles, as well as the structure of spontaneous sleep, were studied in rats 3 weeks after infection with monomorphic Trypanosoma brucei brucei. This parasite belongs to the species of trypanosomes that causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves alterations of endogenous biological rhythms. In the infected rats, entrained to a 12 h:12 h photoperiod, a considerable hypokinesia was detected during the hours of darkness. A significant oscillation of the body temperature during 24 h was lost in some infected animals. In the other infected animals, the body temperature cycle displayed a lower amplitude and a phase advance. The mean temperature was slightly higher in the infected than in control rats during the period of light. A detailed analysis of the structure of spontaneous sleep, based on daytime electroencephalographic recordings, revealed during trypanosome infection an increased relative proportion of wake, and a decreased percent value of synchronized sleep. A marked reduction of the mean REM latency and a fragmented pattern of synchronized sleep, resulting in a considerable alteration of the REM-non-REM sleep sequences, were also observed in the infected animals. These findings indicate that trypanosomiasis in the rat results in a striking sleep fragmentation, as well as in changes of locomotor activity and body temperature rhythm. Thus, trypanosome infection in the rat provides an experimental model of sleep dysregulation in a structurally intact brain, and may provide an animal model of endogenous rhythm changes documented in African sleeping sickness.

Analysis of Variance↗

Filippo Pacini: a determined observer.

The life of Filippo Pacini (1812-1883) and his major scientific achievements are outlined. Pacini drew attention to the corpuscles named after him in 1831, when he was a medical student, and had to struggle for many years to convince the scientific community of the reliability and importance of his findings. In 1849 Pacini became professor of anatomy at the University of Florence. Creative scientist, innovative teacher, well aware that the use of the microscope represented a revolutionary approach, Pacini pursued histological studies until his death. He also first discovered in 1854 (30 years before Robert Koch) the causative agent of cholera, and firmly believed that the disease was contagious. Strong-willed, modest, and poor, Pacini received from his colleagues more recognition in the obituaries than during his life.

Eponyms↗

Fos expression in the spinal cord is suppressed in rats displaying conditioned hypoalgesia.

Two experiments used c-fos expression as a marker of spinal nociceptive processing to study the neural correlates of hypoalgesic responses to conditioned stimuli (CSs) paired with an aversive event. Immunoreactive (ir) neuronal labeling of Fos, the nuclear protein encoded by the c-fos gene, was examined in the spinal cords of rats killed 2 hr after injection of dilute formalin into a hind paw. Compared with control rats either not conditioned or conditioned in one environment but tested elsewhere, there were significantly fewer Fos-ir neurons in the spinal cords of rats displaying hypoalgesic responses when tested in the presence of aversive CSs. Naloxone abolished hypoalgesic responses and reinstated spinal Fos expression, indicating that aversive CSs activated opioid-based antinociceptive mechanisms. The results confirm that aversive CSs produce hypoalgesia by inhibiting the transmission of ascending nociceptive information.

Animals↗

Neuronal IFN-gamma in tuberomammillary neurones.

Neuronal interferon-gamma (N-IFN-gamma), recently isolated from the nervous system, has a molecular weight distinct from that of lymphocyte-derived IFN-gamma, but crossreacts immunologically and shares certain bioactivities with this cytokine. In the rat brain N-IFN-gamma-immunoreactive perikarya were concentrated in the hypothalamic tuberomammillary nuclei; some immunostained neurones were also detected in the dorsal pontine tegmentum. Immunopositive nerve fibres were profusely distributed through the periventricular hypothalamus and midline thalamus. Scattered fibres occurred diffusely through the brain, ramified in the subpial layer and also surrounded intrathecal vessels. A dense concentration of puncta was detected in the suprachiasmatic nuclei and in the molecular layer of the hippocampal dentate gyrus. A role of N-IFN-gamma in immunological reactions and in modulation of selective brain functions is suggested.

Animals↗

Dysregulation of photic induction of Fos-related protein in the biological clock during experimental trypanosomiasis.

The mammalian suprachiasmatic nuclei of the hypothalamus (SCN) serve as pacemaker for circadian rhythms and the immediate-early gene c-fos is known to be induced by photic stimulation in the SCN of rodents. We studied the induction of Fos-related protein following a light pulse in rats infected with Trypanosoma brucei. This parasite causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves changes of endogenous biological rhythms. Fos-like immunoreactivity after photic stimulation was dramatically reduced in the SCN of trypanosome- infected rats during the subjective night. These findings indicate that the photic entrainment of the biological clock may be altered during the infection.

Animals↗

Trypanosomes cause dysregulation of c-fos expression in the rat suprachiasmatic nucleus.

Rats infected with the parasite Trypanosoma brucei brucei showed selective changes of c-fos expression in the suprachiasmatic nucleus of the hypothalamus (SCN) during spontaneous sleep (S) and wakefulness (W) under a basal 12 h/12 h light-dark (L-D) cycle. In the vast majority of W (D phase) control animals the SCN was devoid of cells displaying Fos-related immunopositivity, while Fos-like-immunoreactive (ir) neurones were detected in most S (L phase) control rats. In most infected animals, on the other hand, Fos-ir neurones were detected in the SCN during W, but not during the S period, with a significant difference between control and infected S rats. Thus, these data indicate that the basal c-fos expression in the SCN during the L-D and S-W cycles is considerably altered in experimental trypanosomiasis. This is the first observation of a selective change in the SCN in trypanosome-infected rat brains. Since the SCN plays an important role as a pace-maker for biological rhythms, this finding may provide a basis for understanding the pathogenesis behind endogenous rhythm dyregulation and changes in sleeping pattern in human trypanosomiasis (African sleeping sickness).

Animals↗

Co-localization of nitric oxide synthase and NGF receptor in neurons in the medial septal and diagonal band nuclei of the rat.

The relationship of neurons that express nitric oxide synthase type I (NOS-I), the synthetic enzyme of the free radical nitric oxide (NO), with cells that contain the low affinity p75 nerve growth factor receptor (NGFr) was examined in the basal forebrain region of the rat using double immunohistofluorescence. NOS and NGFr were found to be co-localized in a neuronal population that displayed a selective distribution. Double immunopositive neurons were evident in the medial septum and in rostral levels of the diagonal band nuclei where the vast majority (more than 80%) of NOS-immunoreactive cells were also NGFr-positive; the two cell populations were separate at more caudal levels of the basal forebrain. These findings support the chemical heterogeneity of septal and basal forebrain neurons which contain NGFr and indicate that in the rat a subset of neurons of the septum-diagonal band complex may release NO.

Amino Acid Oxidoreductases↗