Biomedical subjects

O Prospéro-García

Publications and source records attributed to O Prospéro-García.

16 recordsLinked to original sources

PubMed2001

Oleamide modulates memory in rats.

Oleamide is a recently described lipid, obtained from the cerebrospinal fluid of sleep-deprived cats. It has been observed that oleamide possesses several biological effects, such as sleep induction, and immunological suppression as well as serotonin and gamma-aminobutyric acid receptors activation. In addition, oleamide also binds to the cannabinoid receptors. In this study, we have observed that oleamide facilitates memory extinction in a passive avoidance paradigm, reduces core temperature and pain perception, but does not affect significantly locomotion. These results suggest that oleamide modulates memory processes. However, we do not know if oleamide impairs the retrieval of the memory associated to the "not go" behavior, or facilitates the fast re-learning of the "go" behavior. In addition, since these effects are also induced by marijuana and anandamide, it is very likely that oleamide may be affecting the cerebral cannabinoid system to induce its effects.

Animals↗

PubMed2001

Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase.

Approximately 35% of HIV-infected subjects, both children and adults, exhibit alterations in the sleep-waking cycle. HIV surface glycoprotein gp120 has been postulated to contribute to this abnormality. For example, it has been reported that HIVgp120 modifies sleep in freely-moving rats and that it also activates the ERK pathway in brain slices. The goal of this work was to determine if sleep changes induced by HIVgp120 in normal rats are mediated by the MAPK pathway. Our results show that a single intraventricular administration of HIVgp120 selectively increases REMS and that such an increase can be prevented by U0126, an inhibitor of ERK activating enzyme, MEK. In contrast, SB202190, a MAPK-p38 inhibitor, had no effect on HIVgp120-induced increase in REMS. These results suggest that HIVgp120 increases REMS in the rat by specifically affecting the ERK signal transduction pathway.

AIDS Dementia Complex↗

PubMed2001

Anandamide-induced sleep is blocked by SR141716A, a CB1 receptor antagonist and by U73122, a phospholipase C inhibitor.

Anandamide (ANA) alters sleep by increasing the amount of time spent in slow wave sleep 2 (SWS2) and rapid eye movement sleep (REMS) at the expense of wakefulness (W) in rats. In this report, we describe a similar effect of ANA when injected itracerebroventricularly (i.c.v.) or into the peduriculopontine tegmental nucleus (PPTg) and the lack of an effect when ANA is administered into the medial preoptic area (MPOA). Furthermore, the i.c.v. or PPTg administration of SR141716A, a CB1 antagonist, or U73122, a PLC inhibitor, 15 min prior to ANA, readily prevents the ANA induced changes in sleep. The present results suggest that a cannabinoid system in the PPTg may be involved in sleep regulation and that the cannabinoid effect is mediated by the CB1 receptor coupled to a PLC second messenger system.

Animals↗

PubMed2000

HIV-derived protein gp120 suppresses P3 potential in rats: potential implications in HIV-associated dementia.

Between 20 and 30% of AIDS patients have neurological symptoms characterized by motor impairment, memory loss and progressive dementia. Previous studies have implicated the HIV derived gp120, which produces behavioral deficits and electrophysiological alterations in rats. The goal of the present study was to describe the effect of this protein on the P3 event-related potential (ERP), evoked by a passive discrimination task in rats. We used II rats divided into two groups: HIV gp120 (n = 6) and control (n = 5). We recorded the P3 wave before any treatment (baseline), during the i.c.v. administration of either HIVgp 120 (700 ng/5 days) or saline (pH 7.2), and 24 h, 7, 14 and 21 days after the last injection. There were no changes between groups in the amplitude or latencies of the observed components (N1, P2, N2 and P3) evoked by target stimuli, during baseline or during the injection period. However, the HIV gp120 group showed a significant amplitude reduction in P3 wave 24 h after the last injection, while the N1, P2 and N2 waves remained unchanged. However, from the 7th day through the 21st day, P2 and N2 components also disappeared and only the N1 component could be observed in the HIV gp 20-treated group. These changes in the N2, P2 and P3 potentials, suggesting an alteration in cognitive processes, further support the neurotoxic activity of HIV gp120 and its role in AIDS dementia.

AIDS Dementia Complex↗

PubMed2000

Cortistatin modulates memory processes in rats.

Cortistatin (CST) is a recently described neuropeptide with high structural homology with somatostatin. Its mRNA is restricted to gamma amino butyric acid (GABA)-containing cells in the cerebral cortex and hippocampus. CST modulates the electrophysiology of the hippocampus and cerebral cortex of rats; hence, it may be modulating mnemonic processes. In this study, we have evaluated the effect of CST and somatostatin (SS) on short- and long-term memory (STM and LTM, respectively), as well as on the extinction of the behavior by using the footshock passive avoidance behavioral test. In addition, we tested the ability of both neuropeptides to affect the generation of cAMP in hippocampal neurons in culture. Results showed that the administration of either CST or SS into the hippocampal CA1 deteriorates memory consolidation in a dose-response fashion and facilitates the extinction of the learned behavior. CST was more potent than SS. Likewise, CST increases cAMP while SS decreases it. These results strongly support a modulatory role for CST in memory processes.

Animals↗

PubMed2000

HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats.

Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in 20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived from HIV seems to play a critical role in the pathophysiology of this dementia. Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes neurological and electrophysiological abnormalitites in cats. We have studied the effects of gp120 derived from HIV or FIV on learning and memory processing, hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production, the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results showed that while both HIV- and FIV-gp120 impaired the rat's performance in the Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP. However, both glycoproteins induced a significant decrease in the posttetanic potentiation. HIVgp120 also caused a significant reduction in cAMP production in the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM sleep. Locomotor activity and equilibrium were significantly altered by these glycoproteins. These results suggest that HIVgp120 causes neurophysiological abnormalities and therefore may facilitate HAD development in AIDS patients.

AIDS Dementia Complex↗

PubMed1999

Feline immunodeficiency virus envelope protein (FIVgp120) causes electrophysiological alterations in rats.

Close to 20% of the patients infected with the AIDS virus develops neurological deficit; eventhough HIV does not invade neurons. Consistently with the neurological deficit, HIV(+) subjects show abnormalities in brainstem auditory and visual evoked potentials (BSAEP and VEP) and in sleep patterns. The HIV-derived glycoprotein 120 has been postulated as a neurotoxic; therefore, it may be playing a crucial role in the generation of BSAEP and VEP, as well as in sleep disturbances. To study the role of the virus-derived proteins on the development of these electrophysiological signals' alterations, we have used the feline immunodeficiency virus (FIV)-derived gp120 and evaluated the changes in these electrophysiological signals. We employed 15 adult male Sprague-Dawley rats (250-350 g), chronically implanted for evoked potential and sleep recordings. Results showed that the i.c.v. administration of FIVgp120 (5 ng/10 microliter) produces changes in the latency of both cortical auditory evoked potentials (CAEPs) and VEPs and a decrease in both REM sleep and SWS. These data support the notion that FIVgp120 is neurotoxic to the central nervous system of cats and rats and that this protein suffices to cause electrophysiological alterations. In addition, it suggests that a similar effect may be occurring in humans as a result of HIVgp120's neurotoxic effects.

Analysis of Variance↗

PubMed1998

Anandamide modulates sleep and memory in rats.

In this study we have assessed the effect of the intracerebroventricular administration of anandamide (ANA) as well as its precursor metabolite arachidonic acid (AA), on the sleep-wakefulness cycle, memory formation, locomotor activity and pain perception. Our results have indicated that ANA strikingly increases slow-wave sleep (SWS)2 and rapid-eye movement (REM) sleep at the expense of wakefulness (W); while deteriorating memory consolidation. ANA also increases locomotor activity but does not modify pain perception threshold. In contrast, AA increases W and reduces SWS2, while deteriorating memory consolidation and increasing locomotor activity. AA has no effect on pain perception. These results suggest that the brain cannabinoid system participates in the modulation of the vigilance states and mnemonic processes. Additionally, they suggest that the effect on pain perception may be a peripheral rather than a central effect.

Analysis of Variance↗

PubMed1996

Microglia-passaged simian immunodeficiency virus induces neurophysiological abnormalities in monkeys.

Four rhesus macaques were inoculated intravenously with a cryopreserved stock of microglia obtained from a simian immunodeficiency virus (SIV)-infected rhesus macaque. Before infection, three of the four monkeys were trained and tested daily on a computerized neuropsychological test battery. After SIV infection, behavioral testing continued to monitor deficits associated with disease progression. Five additional age-matched, behaviorally trained monkeys served as controls. Neurophysiological testing for visual and auditory evoked responses was accomplished 37-52 weeks after infection in all monkeys. Subsequently, all four SIV-infected monkeys and one control subject were sacrificed, and samples of brain tissue were taken for pathological analysis. SIV-infected monkeys demonstrated abnormal responses in both auditory and visual evoked responses. In addition, around the time of electrophysiological recording, all three SIV-infected, behaviorally trained monkeys exhibited significant decreases in progressive-ratio performance, reflecting a reduction in reinforcer efficacy. One subject also demonstrated impairments in shifting of attentional set and motor ability at that time. Neuropathological evaluation revealed that all four SIV-infected monkeys exhibited numerous perivascular and parenchymal infiltrating T cells. These findings document that SIV causes electrophysiological, behavioral, and neuropathological sequelae similar to what has been observed in the human neuroAIDS syndrome. Our observations further validate the simian model for the investigation of the pathogenesis of AIDS dementia and for the investigation of drugs with potential therapeutic benefits.

AIDS Dementia Complex↗

PubMed1994

Sleep patterns are disturbed in cats infected with feline immunodeficiency virus.

Human immunodeficiency virus (HIV)-related sleep disturbances have been reported early in AIDS. Likewise, the feline immunodeficiency virus (FIV), a natural lentivirus pathogen of cats, produces a similar immunodeficiency syndrome with neurological sequelae. To identify the neurophysiological substrate of FIV infection in brain, pathogen-free cats were infected with the Maryland strain of FIV. Eight weeks after inoculation, all FIV-infected cats seroconverted and virus was detected in the cerebrospinal fluid and in the mononuclear cells of peripheral blood. Ten to 12 months after the FIV inoculation, inoculated and control cats were surgically implanted with electrodes to record the sleep/wake cycle. These sleep recordings were obtained under conditions controlling for environmental variables and instrumental adaptation. FIV-infected cats spent 50% more time awake than the sham-inoculated controls and exhibited many more sleep/waking stage shifts--i.e., 40% more than controls. In addition, FIV-infected cats showed approximately 30% of rapid eye movement (REM) sleep reduction compared to controls. The latency to sleep and REM sleep onset was also significantly delayed in FIV-infected cats. In addition, a remarkable increase in cortically recorded spindle activity (8-13 Hz) was observed during slow-wave sleep in some infected subjects, similar to changes described in HIV-infected humans. Moreover, infected cats exhibited no overt signs of systemic morbidity, such as hyperpyrexia or body weight loss. These results indicate that FIV-infected cats exhibit sleep abnormalities similar to the sleep disturbances previously described in AIDS patients and further support the feline preparation as a valuable animal model of HIV infection of the central nervous system.

Animals↗

PubMed1994

Intraventricular administration of a FIV-envelope protein induces sleep architecture changes in rats.

Fifteen adult male Sprague-Dawley rats were implanted with a set of electrodes for standard sleep recordings. A stainless steel cannula was also implanted into the lateral ventricle of these rats. Fifteen additional rats were implanted with a cannula alone. Rats with electrodes were habituated for 3 days or more to the recording environment, then placed into 3 groups (n = 5). One group received saline (i.c.v.), while the other two groups received either the feline immunodeficiency virus envelope glycoprotein (FIV SU-Env) or a fragment of the Epstein-Barr virus envelope glycoprotein (EB gp105). Rats were then recorded for electrographic sleep-wake cycle evaluation for the following 4 h. Core temperature was assessed through a thermistor probe inserted into the rectum, immediately before and 1, 2, 3 and 4 h after the i.c.v. treatment condition. Results demonstrated that compared to saline, FIV SU-Env increased wakefulness and decreased REM sleep throughout the 4 h of recording. Likewise, FIV SU-Env decreased SWS2 for 2 h. In addition, EB gp105 administration elicited minor modifications of the sleep-wake cycle, causing only a transient reduction of REM sleep in the first hour of recording. None of the treatments altered body temperature. These findings strongly support and extend studies in FIV-infected cats in which we have found similar sleep abnormalities. In addition, these results are consistent with the hypothesis that the FIV SU-Env proteins are responsible for these neurological disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Hippocampal interneuron activity in unanesthetized rats: relationship to the sleep-wake cycle.

Evoked population spikes and interneuronal discharges were recorded throughout the sleep-wake cycle in hippocampal regions CA1 and dentate gyrus (DG) of ten chronically implanted rats. During quiet wakefulness (QW) and slow-wave-sleep (SWS) (non-theta rhythm states), the primary shock of paired stimuli evoked in CA1 both high amplitude population spikes and multiple interneuron discharges when compared to active wakefulness (AW) and rapid-eye-movement (REM) sleep (theta rhythm states). A second shock was delivered to CA1 afferents 60 ms after the first shock. This second shock evoked a small population spikes during non-theta states, whereas it evoked higher amplitude population spikes in theta states. The second shock also evoked unit interneuron discharges in non-theta states but not in theta states. In the dentate gyrus, identical primary afferent stimulation evoked similar interneuron activity and uniform amplitude population spikes throughout the sleep-wake cycle. In contrast, the secondary shocks evoked a striking potentiation of the field population spike during sleep, SWS and REM sleep compared to AW and OW. Evoked DG interneuron spikes following the second population spike were greater in number during SWS compared to the other stages. Our findings suggest that hippocampal field potentials and interneuron activity recorded in vivo are regionally regulated, have unique state-dependent expression and are strongly influenced by inhibitory feed-forward mechanisms.

Activity Cycles↗

PubMed1990

Vasoactive intestinal polypeptide induces REM recovery in insomniac forebrain lesioned cats.

Basal forebrain (BF) lesions in cats produces insomnia by reducing both slow wave sleep (SWS) and rapid-eye-movement (REM) sleep time. Recently it has been shown that vasoactive intestinal polypeptide (VIP) may be a specific REM inductor in the parachlorophenylalanine (PCPA) insomniac model. The purpose of this study was to test the hypnogenic properties of VIP in a nonpharmacological model of insomnia. Cats were rendered insomniac by delivering a DC current through stainless steel tripolar electrodes implanted in the basal forebrain area (BFA). Sleep-waking cycle recordings were done prior to lesions and on days 7, 9, 10, 11, 14, and 21 days after BF lesion. On day 10 after the lesion, 200 ng of VIP was injected into the 4th ventricle. Results showed that on postlesion days 7 and 9, SWS and REM sleep total times decreased, while waking time increased significantly. VIP restored REM sleep total time and frequency for almost 48 h, and SWS sleep total time for 24 h. On days 14 and 21 postlesion, insomnia was reestablished. Results are discussed in terms of the possible anatomical and neurochemical substrates whereby VIP can induce the recovery of sleep-waking control values.

Animals↗

PubMed1988

Microinjection of carbachol into the pontine area is unable to modify insomnia induced by p-cholorophenylalanine (PCPA).

It has previously been shown that cholinergic drugs administered into the pontine area (field tegmental gigantocellular, FTG) are capable of inducing significant increases of rapid eye movement (REM) sleep periods in normal cats. The purpose of this study was to determine whether such cholinergic stimulation is capable of inducing similar effects in p-chlorophenylalanine (PCPA) insomniac cats. Four groups (n = 6) of cats were used in this study. The first two groups received a microinjection of either, saline (1 microliter) or carbachol (8 micrograms/1 microliter). The last two groups, prior to the microinjection, received PCPA (400 mg/kg) pre-treatment. Histological analysis showed that the tips of the cannulae were located in the caudal FTG, at the level of the ponto-medullary union. Results showed that carbachol significantly increased REM sleep in normal cats as compared to saline, whereas, carbachol was unable to modify the insomnia induced by PCPA. These findings suggest that cholinergic effects on REM sleep require a serotoninergic system. The results are discussed in terms of acetylcholine/serotonin interaction in the control of REM sleep.

Animals↗

PubMed1987

Cerebroventricular infusion of cholecystokinin (CCK-8) restores REM sleep in parachlorophenylalanine (PCPA)-pretreated cats.

Recently, some studies have shown that cholecystokinin (CCK-8) administered either intraventricularly or intraperitoneally has no effect on sleep. However, since in such studies CCK-8 was given at times when sleep predominates, in this study the effects of CCK-8 on sleep were determined in parachlorophenylalanine (PCPA) (400 mg/kg)-pretreated insomniac cats. Twenty-four hours after the second injection of PCPA one group of cats received 100 ng/100 microliter of CCK-8 and another group only 100 microliter of saline. A third group was studied only under the effects of PCPA. The results showed that CCK-8 was capable of restoring sleep in the otherwise insomniac cats and that this effect was restricted to REM sleep only. The observed REM sleep-promoting action of CCK-8 supports the notion that this polypeptide may be involved in REM sleep regulation.

Animals↗

PubMed1987

Rapid eye movement (REM) sleep and ponto-geniculo-occipital (PGO) spike density are increased by somatic stimulation.

It has been shown that REM sleep duration and ponto-geniculo-occipital (PGO) spike density can be enhanced by auditory stimulation. The purpose of this study was to determine whether this effect is restricted to the auditory sensory modality or whether somatic stimulation can produce similar effects. Cats implanted with electrodes for recording the sleep-wake cycle were additionally prepared with clip electrodes placed in the neck for somatic stimulation. Such stimulus was applied at the beginning and throughout each REM sleep period. The effect of this procedure was compared to a similar period when no stimulus was applied. The results showed that somatic stimulation induced a significant increase in REM duration (60.2%) and PGO spike density. Since the effects of somatic stimuli are identical to auditory ones, it is suggested that all sensory modalities may share the property of influencing the mechanisms which regulate the maintenance of REM sleep. Such mechanisms are discussed in terms of an increase in the excitability levels of polymodal medial reticular neurons.

Acoustic Stimulation↗