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G Nisticò

Publications and source records attributed to G Nisticò.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

Different profile of electrocortical power spectrum changes after micro-infusion into the locus coeruleus of selective agonists at various opioid receptor subtypes in rats.

1. The effects of various opioid receptor agonists given directly by means of a chronically implanted cannula into the locus coeruleus (LC) on behaviour and ECoG activity, continuously analysed, and quantified as total power spectrum (0-16 Hz) and in preselected frequency bands (0-3; 3-6; 6-9; 9-12 and 12-16 Hz), were studied in rats. 2. Dermorphin (0.05, 0.5, 1, 2 and 5 pmol) and Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO; 1, 10, 30, 100 pmol and 1 nmol), two typical mu-receptor agonists, applied unilaterally or bilaterally directly into the LC, produced a typical dose-dependent ECoG synchronization with a significant increase in total power spectrum as well as in the lower frequency bands. Dermorphin was found to be approximately 30 times more powerful than DAMGO in producing similar quantitative ECoG changes. 3. D-Ala-D-Leu-Thr-Gly-Gly-Phe-Leu (DADLE; 1, 10, 50 and 100 pmol), a selective delta-receptor agonist, micro-infused into the LC produced dose-dependent behavioural soporific effects and ECoG increase in total power spectrum as well as in 3-6, 6-9, 9-12 Hz frequency bands. In comparison to dermorphin, the ECoG power spectrum effects of DADLE were 10 fold less potent, whereas in comparison to DAMGO it was approximately 3 times more potent. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 4. The microinfusion into the LC of U 50, 488H, a selective Kappa-opioid receptor agonist, (0.25, 1, 2.5, 5 and lOpmol) produced a typical pattern characterized by a first short-lasting (3-25 min) phase of behavioural arousal and ECoG desynchronization, followed by a longer lasting (20-130min according to the dose) phase of behavioural sleep and ECoG synchronization. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 5. Dextromethorphan and ketamine, two selective agonists at sigma-receptors given into the LC (1, 5 and 1Opmol) induce behavioural arousal, increase in locomotor activity and an intense pattern of stereotypedm movements. However, by increasing the dose of ketamine (50 and lOOpmol), marked sedation, postural changes and an increase in low frequency ECoG bands, sometimes associated with high amplitude fast frequency potentials, were observed. 6. Naloxone applied directly into the LC (1 and 2 pmol 15min before) was able to prevent the behavioural and ECoG effects induced by dermorphin, DAMGO and DADLE. Higher doses of naloxone (1Opmol into the LC) were however, required to antagonize the behavioural and ECoG soporific effects induced by the Kappa-receptor agonist U 50,488H. In contrast, naloxone (1Opmol into the LC) was unable to prevent or reduce the behavioural and ECoG effects induced by subsequent administration into the same site of dextromethorphan and ketamine. 7. In conclusion, the present experiments confirm that behavioural and ECoG effects elicited following stimulation of mu-, delta-, Kappa- and sigma-opioid receptors located in the LC are quite different. Activation of ,mu-, band Kappa-receptors induced sedative effects whereas dextromethorphan and ketamine, two sigma-receptor agonists, induced behavioural arousal and ECoG desynchronization. In addition, the present results strongly support the crucial role played by opioid mechanisms, in the locus coeruleus, in the mediation of the soporific effects of drugs acting as agonists at opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus.

1. The behavioural and neuropathological effects of tetanus toxin, microinjected directly into the hippocampus, were studied in rats. 2. A single dose (1000 minimum lethal doses, MLDs) of tetanus toxin, injected unilaterally into the hippocampus produced a time-dependent neuronal loss in the CA1 pyramidal cell layer. In comparison with the contralateral, untreated side these effects became statistically significant (P less than 0.05) 7 days (22.0 +/- 1.1% reduction) and 10 days (29.2 +/- 1.7% reduction) after the injection. No significant changes were observed 7 days after treatment with 500 MLDs whereas a reduction of 37.5 +/- 3.1% in the CA1 area cell number was produced 4 days after the injection of 2000 MLDs. 3. Behavioral stimulatory effects were also induced by tetanus toxin (1000 MLDs) within 48 h of the injection and these culminated in generalized convulsions 5-7 days later. Convulsions were observed after a shorter period of latency in rats receiving 2000 MLDs tetanus toxin whereas 500 MLDs were ineffective. 4. No behavioural and neuropathological effects were observed in rats treated with neutralized tetanus toxin (1000 MLDs), bovine serum albumin or phosphate buffer. 5. Pretreatment with MK801 (0.3 mg kg-1, i.p., given 1 h before and after the injection with tetanus toxin and then once daily for 4 or 7 days) prevented the behavioural and neuropathological effects induced by tetanus toxin (1000-2000 MLDs). In addition, such treatment fully protected the animals from the lethal effects induced by 1000 MLDs tetanus toxin. In addition, such treatment fully protected the animals from the lethal effects induced by 1000MLDs tetanus toxin. By contrast, pretreatment with diazepam (3.Omgkg-1, i.p.) using the same schedule as for MK801 did not antagonize the effects of tetanus toxin (1000-2000 MLDs). 6. In conclusion, the present experiments have demonstrated that the intrahippocampal injection of tetanus toxin produces in rats a dose- and time-dependent behavioural stimulation and neuronal loss in the CAl pyramidal cell layer which can be prevented by the non-competitive NMDA antagonist, MK801.

Animals↗
PubMed1990

The effects of phosphatidylserine on the decreased cardiovascular response to clonidine microinfused into the nucleus tractus solitarii of old rats.

1. The cardiovascular effects of direct microinfusions of clonidine into the nucleus tractus solitarii (NTS) in rats of different ages were studied. 2. Clonidine microinfused into the NTS produced a dose-dependent hypotensive and bradycardic response, which was reduced by previous microinfusion of yohimbine but not of propranolol or prazosin. 3. Unilateral microinfusion of clonidine into the NTS produced a significantly smaller hypotensive and bradycardic response in 16 month old rats than in 3 month old rats, whereas in older animals (24 month old) the same doses of clonidine were ineffective. In 16 month old rats, yohimbine given into the NTS produced a smaller pressor and tachycardic response than in 3 month old rats whereas in 24 month old animals yohimbine, at the same doses, was unable to change blood pressure and heart rate. 4. Oral administration of phosphatidylserine (50 mg kg-1 day-1 for 30 consecutive days) enhanced the hypotensive and bradycardic response to clonidine microinfused into the NTS in 16 month old rats. The same schedule of treatment with phosphatidylserine did not affect the cardiovascular response to clonidine in young (3 month old) rats and did not restore responsiveness to clonidine in older rats (24 month old). 5. Methoxamine and phentolamine, given intravenously, produced similar pressor and depressor responses, respectively in 3, 16 and 24 month old rats, suggesting that the decreased sensitivity to clonidine in old rats was not due to peripheral cardiovascular changes. 6. In conclusion, the present results indicate that, during aging, there is a decreased sensitivity of alpha 2-adrenoceptors in the brain. Such an alteration can be reversed by chronic treatment with phosphatidylserine during the initial but not the later stages of aging.

Aging↗
PubMed1990

Naloxone antagonizes behavioural and ECoG effects induced by systemic or intracerebral administration of some lymphokines.

Rat interferon, alpha-interferon, interleukin-2 and recombinant interleukin-2 microinjected into the third cerebral ventricle produced in rats typical behavioural sedation and/or sleep and ECoG synchronization while beta-interferon produced no behavioural sleep and ECoG synchronization. A slight sedation was observed after highest dose of beta-interferon only. During sleep induced by these lymphokines a dose-dependent increase in total voltage power as well as in the 0.5-3, 4-7 and 12-16 Hz frequency bands was observed. Much lower doses were required to produce similar behavioural and ECoG spectrum power effects after microinfusion of interferons and interleukin-2 into the locus coeruleus. No significant behavioural and ECoG changes were obtained after microinfusion of the same doses of interferons and interleukin-2 into other areas of the brain (caudate nucleus, dorsal hippocampus, substantia nigra-pars compacta-, ventromedial hypothalamus). The behavioural and ECoG effects of alpha-interferon, rat interferon and interleukin-2 were blocked in animals pretreated with naloxone. These results are consistent with the hypothesis that the behavioural and ECoG effects of these lymphokines are mediated at locus coeruleus level via a stimulation of opiate receptors.

Animals↗