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Biomedical subjects

G Nisticò

Publications and source records attributed to G Nisticò.

At least 19 recordsLinked to original sources
PubMed1992

Altered sensitivity of alpha 2-adrenoceptors in the brain during aging in rats.

The soporific and cardiovascular responses to the injection of clonidine into the locus coeruleus and nucleus tractus solitarius, respectively, were studied in rats of different ages. Clonidine (0.09, 0.19, 0.28, and 0.56 nmol) microinfused into the LC of young rats induced dose-dependent behavioral and ECoG SWS with a significant increase in total voltage in the lower frequency bands. In contrast to young rats, clonidine (0.19 and 0.28 nmol) given into the LC did not affect the behavior and ECoG spectrum power in old rats. However, after higher doses of clonidine (0.56 and 1.2 nmol) a small, short-lasting period of behavioral and ECoG SWS was still evident. In 3-month-old rats clonidine (0.25, 0.5 and 1 micrograms) injected into the nucleus tractus solitarius in anesthetized rats produced a significant fall in blood pressure and a significant decrease in heart rate. In contrast, in 12-month-old rats the maximum fall in blood pressure and heart rate was significantly less than in young animals. In addition, in older rats (24-month old) clonidine at the same or larger doses given into the nucleus tractus solitarius did not produce any significant changes in the cardiovascular parameters studied. In conclusion, the present experiments provide evidence that during aging there is a progressive decrease in the soporific and cardiovascular responses to alpha 2-adrenoceptor stimulation in the locus coeruleus and nucleus tractus solitarius, respectively.

Aging↗
PubMed1992

Evidence that CHP100 neuroblastoma cell death induced by N-methyl-D-aspartate involves L-arginine-nitric oxide pathway activation.

Evidence suggests that nitric oxide (NO) may mediate, at least in part, excitotoxic effects of excessive N-methyl-D-aspartate (NMDA) receptor activation both in vivo and in vitro. In the present experiments, NMDA-induced excitotoxicity has been studied in CHP100 neuroblastoma cell cultures. Application of NMDA (0.25-1.5 mM) produced concentration-dependent cell death. These effects were antagonized by co-application of dizocilpine (MK801), a selective and non-competitive NMDA receptor complex antagonist. Protection from NMDA-induced lethal effects was also afforded by N omega-nitro-L-arginine methyl ester, a potent NO-synthase inhibitor, and by hemoglobin, a NO-trapping agent. In addition, substitution of L-arginine, normally present in the exposure solution with its D-isomer, abolished the cell death induced by the excitotoxin. In conclusion, the present experiments support the suggestion that excitotoxic effects induced by NMDA receptor stimulation involve L-arginine-NO pathway activation.

Amino Acid Oxidoreductases↗
PubMed1992

Tacrine-induced seizures and brain damage in LiCl-treated rats can be prevented by N omega-nitro-L-arginine methyl ester.

The effects of tacrine (5 mg/kg i.p.), a potent acetylcholinesterase inhibitor, were studied in rats pretreated (24 h beforehand) with a single dose (12 mEq/kg i.p.) of LiCl. Tacrine and LiCl were ineffective when given individually. Tacrine elicited seizures and brain damage in 90% of the rats treated. The intracerebroventricular microinfusion of N omega-nitro-L-arginine methyl ester (300 micrograms given 24 h after LiCl administration) significantly reduced the seizures and brain damage produced by tacrine (given 15 min later). These experiments suggest that the seizures and brain damage elicited by tacrine may be due, in part, to increased nitric oxide production in the brain.

Animals↗
PubMed1992

Epileptogenic effects of skin extracts from the Australian frog Pseudophryne coriacea after intracerebral microinfusion in rats.

The behavioural and electrocortical (ECoG) effects induced by a methanol extract of the skin of the Australian frog Pseudophryne coriacea, directly microinjected into several areas of the brain, were studied in freely moving rats. Administration of the P. coriacea extract (5, 10, 15 and 20 micrograms) into the dorsal hippocampus produced a dose-dependent and reversible behavioural stimulation and ECoG spikes lasting 20-140 min. Similar but less intense effects were elicited in rats receiving injections into the III cerebral ventricle, amygdala and caudate nucleus. In conclusion, the present experiments show that the skin extract of P. coriacea produces behavioural stimulation and ECoG spikes when injected into the rat brain, the most sensitive area being the hippocampus.

Amphibian Venoms↗
PubMed1992

Glutamate transmission is involved in the mechanisms of neuronal degeneration produced by intrahippocampal tetanus toxin in rats.

Tetanus toxin (TT) blocks GABA-mediated inhibitory neurotransmission in the mammalian CNS via selective inhibition of transmitter release. The loss of central inhibition produces an excitatory focus resembling human limbic epilepsy. We now report that the net excitation caused by an unopposed action of glutamic acid may also produce neuronal degeneration in the rat brain. Anaesthetized rats were placed in a stereotaxic frame and TT (1 microliter dissolved in phosphate buffer, pH 7.0) was injected unilaterally into the dorsal hippocampus. Injection of TT (1000 mouse minimum lethal doses, MLDs; n = 3-6 rats per group) produced time-dependent neuronal loss in the CA1 pyramidal cell layer which was significant (p < 0.05) 7 and 10 days, but not 1 day, after the injection. Systemic treatment with competitive (CGP 37849, 3 mg/kg i.p) or non-competitive (MK801, 0.3 mg/kg i.p.) antagonists at the N-methyl D-aspartate (NMDA) receptor complex 1 h before and 1 h after TT and then once daily for 10 days protected rats from the hippocampal damage produced by TT (1000 MLDs). In addition, in rats bearing a monolateral surgical lesion of the Schaffer collaterals, through which CA1 neurones receive a robust excitatory input from CA3 pyramids, the bilateral injection of TT (1000 MLDs/side) produced significant neuronal loss in the unlesioned hippocampus whereas the contralateral appeared to be preserved. In conclusion, these results demonstrate that excitatory neurotransmission may be involved in the neuropathology elicited by intrahippocampal TT in rats.

2-Amino-5-phosphonovalerate↗
PubMed1992

NGF restores decrease in catalase activity and increases superoxide dismutase and glutathione peroxidase activity in the brain of aged rats.

The effects of ageing on the activity of copper-zinc superoxide dismutase (SOD), selenium-dependent and independent glutathione peroxidase (GSH-Px) and catalase in several areas of the brain in 3-, 12-, and 24-month-old rats were studied. In addition, the effects of a subacute intracerebroventricular treatment of NGF (1 microgram daily for 28 consecutive days) on SOD, GSH-Px, and catalase activity in the same areas of the brain were assessed. The effects of ageing on the activities of antioxidant enzymes varied considerably in the different brain areas studied. Copper-zinc SOD was alone in being unaffected by ageing. Intraventricular infusion of NGF significantly increased SOD activity in the prefrontal cortex, hypothalamus, caudate nucleus, and mesencephalon of 24-month-old rats. Selenium-dependent GSH-Px activity did not significantly change in 12-month-old rats but it increased in the lower brain stem of 24-month-old animals. In comparison to vehicle-treated rats, NGF significantly increased selenium-dependent GSH-Px activity in all brain areas studied in 12- and 24-month-old rats. Catalase activity decreased significantly in the majority of the brain areas studied in 12- and 24-month-old rats. NGF completely restored the fall in catalase activity in 12- and 24-month-old animals to levels similar to those occurring in young rats. In conclusion, the present experiments show, for the first time, that long-term intraventricular administration of NGF significantly increases in old animals the activity of key enzymes involved in the metabolic degradation of superoxide radicals and hydrogen peroxide.

Aging↗
PubMed1992

Production of limbic motor seizures and brain damage by systemic and intracerebral injections of paraquat in rats.

The behavioural and neuropathological effects of both systemic and intrahippocampal injections of paraquat dichloride (1,1'-dimethyl 4,4'-bipyridinium dichloride) were studied in rats. Paraquat (0.1-1.0 mumol) injected into the dorsal hippocampus, produced limbic motor seizures within a few minutes of injection followed by neuronal damage in the CA1 and CA3 pyramidal cell layers, pyriform cortex, dentate granule cell layer and in the hilus fascia dentata at 24 hr (n = 9 rats). A smaller dose of paraquat (10 nmol) was ineffective. The effects of intrahippocampal injections of paraquat (1 mumol) were prevented by administering it together with atropine (50 nmol; n = 6 rats) or by giving it 60 min. after MK 801 (0.3 mg.kg-1 intraperitoneally). Systemic injections of paraquat (20-100 mg.kg-1) also produced forelimb clonus and rearing in 10 out of 15 animals. Neuronal cell death was found 24 hr later in 9 of these rats and was restricted to the pyriform cortex, the brain region with the highest concentrations of paraquat. Atropine (150 mg.kg-1 intraperitoneally given 60 min. previously) completely prevented the motor seizures but cell death still occurred in 2 of the 6 animals tested. In conclusion, both systemic and intrahippocampal injections of paraquat produced behavioural excitation accompanied 24 hr later by brain damage and antagonist studies suggested involvement of muscarinic and NMDA receptors in the neurotoxic mechanism.

Animals↗
PubMed1992

Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats.

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1 mumol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of paraquat (0.2-0.4 mumol) into the locus coeruleus, substantia nigra or into the raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are present, respectively, elicited potent excitotoxic effects (n = 6 rats per dose and area). A lower dose (0.01 mumol) of the herbicide or injection of the vehicle (1.0 microliter) did not produce any behavioural, ECoG or neurodegenerative effect. 3 After systemic administration, paraquat (20 mg kg-1 s.c.) evoked limbic motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats neuronal cell death was observed in the pyriform cortex, but not in other brain regions. A dose of 5 mg kg-1 was ineffective. 4 Among the regions of the brain studied, high concentrations of paraquat were detected in the pyriform cortex 24 h after systemic administration (5.0 and 20 mg kg-1 s.c.) lower levels being observed in the caudate nucleus. 5 In conclusion, paraquat, given systemically or intracerebrally in rats produces neurodegenerative effects.

Animals↗
PubMed1991

NGF restores decrease in catalase and increases glutathione peroxidase activity in the brain of aged rats.

The effects of subchronic administration of nerve growth factor (NGF) into the lateral ventricle on catalase and selenium-dependent glutathione-peroxidase (GSH-Px) activity in several areas of the brain in 3-, 12- and 24-month-old rats were studied. NGF given daily (1 microgram for 28 consecutive days) produced in all brain areas studied a significant increase in catalase activity in 12- and 24-month-old rats. The most important finding was a complete restoration in 12- and 24-month-old rats of catalase activity to levels similar to those occurring in young (3-month-old) rats. In addition, NGF produced in comparison to 3-month-old rats and to same age vehicle-treated rats a significant increase in selenium-dependent GSH-Px in all the brain areas studied in 12- and 24-month-old animals, whereas selenium-independent GSH-Px was unaffected. In conclusion, the present results show that long-term administration of NGF into the lateral ventricle significantly increases in old animals the activity of key enzymes involved in the metabolic degradation of hydrogen peroxide.

Aging↗
PubMed1991

Intra-nigral infusion of Cu-free superoxide dismutase prevents paraquat-induced behavioural stimulation and ECoG epileptogenic discharges in rats.

In adult rats, with cannulae chronically implanted by a stereotactic instrument into the substantia nigra (pars compacta), the electrocortical (ECoG) and behavioural effects elicited by intranigral infusion of paraquat and the prevention of these effects by prior administration into the same site of different types of superoxide dismutase, were studied. Paraquat (50 micrograms) produced an intense pattern of behavioural stimulation, contralateral circling and repetitive discharges of high voltage ECoG spikes. The effects of paraquat were abolished in all of the animals pretreated into the same site with copper-free superoxide dismutase. Pretreatment with native Cu, Zn-superoxide dismutase prolonged significantly the latency of onset but did not prevent the behavioural stimulation and ECoG spikes evoked by paraquat. On the contrary, pretreatment with albumin or saline did not confer any protection against the neurotoxicological changes induced by paraquat. In conclusion, the present experiments showed that motor, ECoG and lethal effects of paraquat were completely prevented by Cu-free superoxide dismutase, suggesting that the central effects of this herbicide are in some way related to the release in the brain of copper and/or other transition metal ions.

Animals↗
PubMed1991

Is interleukin 2 a neuromodulator in the brain?

A bidirectional flow of information exists between the CNS and the neuroendocrine and immune systems, representing an important homeostatic mechanism in the body. Lymphokines and other products of immunocompetent cells seem to play a crucial role in this communication and seem to exert powerful effects on neurones in the brain. In this article, Giuseppe Nisticò and Giovambattista De Sarro describe the central effects following interleukin 2 (IL-2) microinfusion into several areas of the rat brain. The locus coeruleus seems to be the main site in the brain through which IL-2 exerts soporific effects. In addition, the possible transducing mechanisms coupling IL-2 receptor stimulation and the electroencephalogram (EEG) spectrum power responses elicited from the locus coeruleus seem to involve stimulation of specific receptors coupled to adenylate cyclase through a Gi protein.

Animals↗
PubMed1991

Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide.

Increasing evidence suggests a neurotransmitter role for NO in the mammalian CNS. We have now studied the behavioural and electrocortical (ECoG) profile of rats injected into the lateral cerebral ventricle (ICV) with L-arginine (L-arg), the endogenous donor of the guanidino group from which NO physiologically originates. Rats treated with L-arg (up to 300 micrograms) showed behavioural stimulation, ECoG desynchronization with occasional isolated high voltage spikes but not motor seizures. In rats receiving a subconvulsive dose (0.5 microgram) of N-methyl-D-aspartic acid, (NMDA; ICV) the microinjection of L-arg (300 micrograms; 1 min before) resulted in behavioural and ECoG seizures. The latter effects were prevented by co-administrating L-arg with N-nitro-L-arginine (L-NAME), an inhibitor of NO synthesis. In conclusion, L-arg possesses proconvulsant effects probably mediated by an increase in NO synthesis.

Animals↗
PubMed1991

Behavioural, electrocortical spectrum power and body temperature changes after microinfusion of some lymphokines in the rat brain.

Interleukin-1, interleukin-2 and interleukin-3 injected into the third cerebral ventricle produce typical behavioural sedation and/or sleep and ECoG synchronization in rats. Much smaller doses were required to produce similar behavioural and ECoG spectrum power effects after infusion of interleukins into the locus coeruleus. Interleukin-1 and interleukin-3 induced pyrogenic effects while interleukin-2 produced no pyrogenic actions. These effects were blocked by specific anti-interleukin receptors monoclonal antibodies. In addition, naloxone was able to antagonize the central effects of IL-2 but it did not affect the typical changes induced by IL-1. These results are consistent with the hypothesis that the behavioural, body temperature and ECoG changes of these lymphokines are mediated by specific receptors.

Animals↗
PubMed1990

Selective vulnerability of hippocampal CA3 neurones after microinfusion of paraquat into the rat substantia nigra or into the ventral tegmental area.

The neuropathological effects of various doses of paraquat, a widely used herbicide, given directly into different areas of the rat brain, were studied. Paraquat, microinfused into the pars compacta of the substantia nigra (3.2, 16, 32 and 160 nmol), i.e. concentrations of 3.2 to 160 mmol l-1 applied at 1 microliter min-1 for 1 min, produced dose-dependent neuropathological lesions culminating in neuronal necrosis. A particular feature of paraquat neurotoxicity after its microinfusion into the substantia nigra (3.2 mmol per 1 at 1 microliter per min for 1 min) or into the ventral tegmental area (1.6 mmol per 1 at 1 microliter per min for 1 min), but not into other areas of the brain, was a selective vulnerability of hippocampal CA3 neurones consisting initially of a significant decrease of dendritic spines and later in neuronal degeneration and cell loss. No damage occurred after microinfusion of paraquat into other areas of the brain near or distant from the infusion sites. In addition, similar neuropathological alterations occurred in other non-dopaminergic areas, such as the locus coeruleus and some raphe nuclei after direct microinfusion of paraquat into these sites. In conclusion, the above neuropathological findings show that paraquat possesses marked neurotoxicity which, despite its chemical similarity to MPTP, is not selective for dopaminergic neurones.

Animals↗