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R Nisticò

Publications and source records attributed to R Nisticò.

10 recordsLinked to original sources
PubMed2003

Multifaceted roles of nitric oxide in the lateral geniculate nucleus: from visual signal transduction to neuronal apoptosis.

The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside cholinergic, GABA-nergic, istaminergic, serotoninergic, and glutamatergic signals, the LGN contains also fibers and interneurons expressing the enzyme that produces nitric oxide (NO). Here, we review the documented physiological roles of NO in the transmission of visual inputs to the cortex and in the processes of activity-dependent refinement of LGN connections. Moreover we focus on the recently suggested role of NO in processes of neurotoxicity in the LGN. Particular relevance is given to studies documenting that, through an excitotoxic cascade, NO triggers apoptosis in the LGN of new-born rats deprived of vision in one eye. Data are also discussed on a possible role of NO in the mechanisms of LGN neuronal loss induced by glaucoma. We believe that a better understanding of the role of NO in the LGN may contribute to discover new experimental strategies for the treatment of degenerative ophthalmic diseases.

Animals↗
PubMed2003

Apoptosis in the mechanisms of neuronal plasticity in the developing visual system.

Visual experience during early postnatal life is essential for normal development of synaptic connections in the visual system. In fact, altered visual experiences such as monocular deprivation (MD) or abnormal visual stimulation (e.g. strabismus, anisometropia) during this period disrupt the physiologic organization of the visual pathway, leading to loss of visual responses in cortical neurons and reduction in visual acuity of the affected eye, so that it becomes amblyopic. The authors review the main functional and morphologic changes induced by altered visual experiences in the developing visual system and focus on the recent discovery that MD induces apoptotic cell death in the lateral geniculate nucleus of newborn rats. Particular attention is given to the authors' studies documenting that, during development, MD leads retinal terminals to release excessive glutamate in the lateral geniculate nucleus where it elevates nitric oxide and causes DNA fragmentation. The latter event is known to activate poly-(ADP-ribose) polymerase, which in turn may trigger apoptosis. Better understanding of the mechanisms underlying the morphologic changes induced by altered visual experiences during development may open new venues for studying novel neuroprotective strategies for amblyopia and, more generally, for the treatment of ophthalmic diseases associated with neuronal apoptosis.

Amblyopia↗
PubMed2001

Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor.

The HIV-1 coat protein, gp120 (100 ng given intracerebroventricularly (i.c.v.) daily for seven consecutive days) causes DNA fragmentation in the brain neocortex of rat. In neocortical cells bearing ultrastructural features typical of apoptosis, electron microscopy revealed specific immunopositivity for neurofilament cytoskeletal proteins, suggesting the neuronal nature of dying cells. Neuronal apoptosis by gp120 implicates CXCR4 chemokine receptors; in fact, in rats receiving a single daily, non-neurotoxic, dose of SDF-1alpha (0.25 pmoles given i.c.v. for 7 days before gp120), the natural ligand of CXCR4 receptor, apoptosis was significantly hindered. The mechanism of SDF-1alpha protection involves inhibition of gp120-enhanced expression of IL-1beta, a cytokine implicated in the mechanisms of apoptosis induced by the viral protein in the neocortex of rat.

AIDS Dementia Complex↗
PubMed2001

Evidence that increases of mitochondrial immunoreactive IL-1beta by HIV-1 gp120 implicate in situ cleavage of pro-IL-1beta in the neocortex of rat.

Immunoelectron microscopy analysis of brain tissue sections and rat-specific sandwich ELISA allowed the localization of interleukin-1beta (IL-1beta) immunoreactivity in the mitochondria and cytosol of neocortical tissue preparations from the brain of naive, untreated, rats and rats receiving a single daily injection into one lateral cerebral ventricle (i.c.v.) of bovine serum albumin (BSA; 100 ng/day) for seven consecutive days. Interestingly, seven days i.c.v. treatment with the HIV-1 coat protein gp120 (100 ng/day) enhances IL-1beta immunoreactivity in the cellular fractions studied. Elevation of mitochondrial immunoreactive IL-1beta levels seems to originate from the conversion operated by the interleukin converting enzyme (ICE) of mitochondrial pro-IL-1beta; in fact, IL-1beta increases reported in the ELISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1beta 31-kDa band in conjunction with enhanced expression of the p20 component of activated ICE. In conclusion, the present results demonstrate that gp120-enhanced neocortical expression of IL-1beta originates, at least in part, from in situ cleavage of mitochondrial pro-IL-1beta and suggest that this, together with the central role of the mitochondrion in the expression of programmed cell death, may be important for apoptosis induced by the viral coat protein in the brain of rats.

Animals↗
PubMed2000

Apoptosis in the dorsal lateral geniculate nucleus after monocular deprivation involves glutamate signaling, NO production, and PARP activation.

In mammals, visual experience during early postnatal life is critical for normal development of the visual system. Here we report that monocular deprivation for 2, 7, and 14 consecutive days causes p53 accumulation, cell death, and progressive loss of neurones in the dorsal lateral geniculate nucleus (dLGN) of newborn rats and these are prevented by NMDA and non-NMDA glutamate receptor antagonists, and by L-NAME, an inhibitor of nitric oxide synthesis. Monocular deprivation also increases dLGN levels of citrulline, the coproduct of nitric oxide synthesis, and this, as well as cell death and neuronal loss, is abolished by antagonists of glutamate receptors and by L-NAME. Finally, poly-(ADP-ribose) polymerase (PARP) knock-out mice appear to be protected from monocular deprivation-induced cell death. In conclusion, during early postnatal development of the rat visual system monocular deprivation causes excitotoxic, nitric oxide-mediated, cell death in the dLGN that appears to be apoptotic and also requires activation of PARP.

Animals↗
PubMed2000

Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G.

The effects of a single dose of the HIV-1 coat protein gp120 given into one lateral cerebral ventricle (i.c.v.) on the expression of cyclooxygenase type 2 (COX-2) and PGE(2) levels have been studied using Western blotting and ELISA techniques applied to brain tissue extracts obtained from the neocortex of individual rats, one of the regions of the central nervous system where the viral protein causes apoptosis. The results demonstrate that COX-2 expression is almost doubled 6 h after a single dose (100 ng) of gp120 and this is paralleled by a statistically significant elevation of PGE(2). Enhanced COX-2 expression is implicated in the mechanisms of apoptosis evoked by gp120 because the latter is prevented by NS398 (10 mg/kg i.p.), a selective inhibitor of COX-2 activity. Protection is also afforded by NMDA receptor antagonists, such as MK801 (0.3 mg/kg i.p.) and CGP040116 (10 mg/kg i.p.), and by the free radical scavenger, U-74389G (10 mg/kg i.p.), supporting a glutamate-mediated, excitotoxic, mechanism of apoptotic death induced by gp120. These data together with the observation that MK801 failed to prevent gp120-enhanced COX-2 expression indicate that products of the arachidonic cascade may be responsible for elevation of synaptic glutamate leading neocortical cells to oxidative stress and excitotoxic apoptosis.

Animals↗
PubMed1999

Systemic administration of cocaine, given alone or in combination with sensory stimuli, differentially affects L-arginine-nitric oxide metabolism in discrete regions of the brain of rat.

The effect of cocaine on brain regional metabolism of L-arginine to nitric oxide (NO) has been studied in rat by measuring the level of citrulline, the co-product of NO synthesis, using a HPLC based methodology. A single i.p. administration of 1 mg/kg cocaine, and a daily treatment for up to 5 consecutive days, failed to affect significantly citrulline content in the striatum, hippocampus and cortex. By contrast, in these regions of the brain a single or 5-day repeated higher dose of cocaine (10 mg/kg, i.p.) caused a significant increase in the co-product of NO synthesis and this has been abolished in a stereoselective fashion by L-NAME (10 mg/kg i.p. given 30 min before). Under cocaine high dose treatment, 1 h acoustic stimulation, which per se resulted ineffective, enhanced stimulant-induced increases in citrulline content seen in the striatum and abolished the increase of this amino acid observed in the hippocampus and cortex both after single or 5-day repeated injection of cocaine. In conclusion, these data demonstrate that cocaine stimulates the conversion of L-arginine to NO in the brain of rat and this is affected by concomitant exposure to acoustic stimulation.

Acoustic Stimulation↗
PubMed1998

HIV-1 gp120-induced apoptosis in the rat neocortex involves enhanced expression of cyclo-oxygenase type 2 (COX-2).

The effect of subchronic intracerebroventricular (i.c.v.) injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to 7 consecutive days) on cyclooxygenase type 2 (COX-2) expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumin (100 ng, given i.c.v. for up to 7 days) treated animals (n = 6), a single daily injection of the viral protein for 7 consecutive days enhanced the number of COX-2 immunoreactive cells in the brain cortex of rats (n = 6 per group) and this was accompanied by a 50% increase over control PGE2 content in whole brain tissue homogenates (n = 6). In another series of experiments, pretreatment of rats (n = 6) with indomethacin (6.0 mg/kg given i.p. 1 h before gp120 injection), an inhibitor COX activity, prevented apoptotic death typically produced by gp120 in the neocortex of rat suggesting that enhancement of COX-2 expression may be involved in the mechanisms of apoptosis yielded by the HIV-1 coat protein.

Animals↗
PubMedDate not supplied

A computerised tomographic study in DSM-III affective disorders.

The relationship between ventricular brain ratio (VBR) and clinical variables was investigated in 21 DSM-III depressed patients. None of the following dichotomies--major depression vs. dysthymic disorder, suicidal vs. non-suicidal patients, male vs. female patients--showed any statistically significant differences. An association was identified between VBR and age at onset of depression but when current age was controlled such an association failed to reach a statistically significant level except in the group with major depression. When patients were matched with a control group no differences in VBR were seen with age controlled by decade.

Adult↗