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René Drucker-Colín

Publications and source records attributed to René Drucker-Colín.

15 recordsLinked to original sources
PubMed2006

Neuronal precursors within the adult rat subventricular zone differentiate into dopaminergic neurons after substantia nigra lesion and chromaffin cell transplant.

Neurogenesis in the adult mammalian brain continues in the subventricular zone (SVZ). Neuronal precursors from the SVZ migrate along the rostral migratory stream to replace olfactory bulb interneurons. After the destruction of the nigro-striatal pathway (SN-lesion), some SVZ precursors begin to express tyrosine hydroxylase (TH) and neuronal markers (NeuN). Grafting of chromaffin cells (CCs) into the denervated striatum increases the number of TH+ cells (SVZ TH+ cells; Arias-Carrión et al., 2004). This study examines the functional properties of these newly differentiating TH+ cells. Under whole-cell patch-clamp, most SVZ cells recorded from lesioned and grafted animals (either TH+ or TH-) were non-excitable. Nevertheless, a small percentage of SVZ TH+ cells had the electrophysiologic phenotype of mature dopaminergic neurons and showed spontaneous postsynaptic potentials. Dopamine (DA) release was measured in SVZ and striatum from both control and SN-lesioned rats. As expected, 12 weeks after SN lesion, DA release decreased drastically. Nevertheless, 8 weeks after CCs graft, release from the SVZ of SN-lesioned rats recovered, and even surpassed that from control SVZ, suggesting that newly formed SVZ TH+ cells release DA. This study shows for the first time that in response to SN-lesions and CC grafts neural precursors within the SVZ change their developmental program, by not only expressing TH, but more importantly by acquiring excitable properties of mature dopaminergic neurons. Additionally, the release of DA in a Ca(2+)-dependent manner and the attraction of synaptic afferents from neighboring neuronal networks gives further significance to the overall findings, whose potential importance is discussed.

Analysis of Variance↗
PubMed2006

Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats.

Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icv injection of MOD (10 microg/5 microl) the extracellular levels of dopamine (DA) and l-DOPA collected from the nucleus accumbens were increased and decreased, respectively. Separately, the icv administration of MOD (10 microg/5 microl) to rats enhanced wakefulness (W) whereas diminished sleep during 4h. Lastly, the alertness induced by MOD was partially antagonized by the sleep-inducing endocannabinoid anandamide (ANA). We conclude that MOD enhances the extracellular levels of DA, promotes W and its effects on sleep are partially blocked by ANA.

Analysis of Variance↗
PubMed2006

Effect of transcranial magnetic stimulation on oxidative stress induced by 3-nitropropionic acid in cortical synaptosomes.

This study evaluates the effect of transcranial magnetic stimulation (TMS; 60 Hz and 0.7 mT) treatment on 3-nitropropionic acid (20 mg/kg i.p./day for 4 days)-induced oxidative stress in cortical synaptosomes of Wistar rats. The oxidative derangement was confirmed by a high level of lipid peroxidation products and protein carbonyls, together with a decreased in reduced glutathione (GSH) content, catalase and GSH-peroxidase (GSH-Px) activities. Additionally, it was observed a reduction in succinate dehydrogenase (SDH) activity. All changes were partially prevented or reversed by administration of TMS. These results show that TMS reduces oxidative stress in cortical synaptosomes, and suggest that TMS may protect neuronal and maintain synaptic integrity.

Animals↗
PubMed2006

Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats.

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Delta(9)-THC modulates sleep, but no clear evidence on the role of CBD is available. In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 microg/5 microl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 microg/5microl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 microg/5 microl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 microg/2.5 microl, icv) followed 15 min later by CBD (10 microg/2.5 microl). Results showed that the waking properties of CBD were not blocked by ANA. In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures. Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.

Animals↗
PubMed2006

Survival rates through time of hypocretin grafted neurons within their projection site.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, inadvertent transitions from wakefulness to rapid eye movement sleep (so called "sleep-onset REMS period") and cataplexy (sudden bilateral skeletal muscle weakness during waking without impairment of consciousness). This disorder has been recently linked to a loss of hypocretin (HCRT) neurons making narcolepsy a neurodegenerative disease. Neuronal replacement could be used to reverse the symptoms of narcolepsy. Towards this end, we have recently reported that HCRT neurons from rat pups can survive when grafted into the pons of adult rats. Here, we investigate the time-course of survival of grafted HCRT neurons into the pons of adult rats. The HCRT neurons are present only in the lateral hypothalamus, and therefore suspension of cells from this region was derived from 8- to 10-day-old rat pups (donor), and grafted into the pons of adult (60 days old) host rats. Control rats received a transplant that consisted of cells from the cerebellum where no HCRT neurons are present. All adult host rats were sacrificed 1, 3, 6, 9, 12, 24, or 36 days after grafting. Immunohistochemistry was used to identify and count the presence of the HCRT grafted neurons in the target area. The tally of HCRT neurons present in the graft zone 1 day post-grafting was considered to be the baseline. From day 3 to 36 post-transplant there was a steady decline in the number of HCRT neurons. We also noted that on day 36, the HCRT neurons that survived in the pons had morphological features that were similar to mature HCRT neurons in the adult lateral hypothalamus, suggesting that these neurons might be functionally active. Control rats that received grafts of cerebellar tissue did not show HCRT neurons in the target area. These results demonstrate that there is a progressive decline in the number of transplanted neurons, but a significant percentage of HCRT neurons do survive until day 36. This study highlights the potential use of transplants as a therapeutical tool in order to treat narcolepsy.

Animals↗
PubMed2006

Transcranial magnetic stimulation attenuates cell loss and oxidative damage in the striatum induced in the 3-nitropropionic model of Huntington's disease.

An investigation was conducted on the effect of transcranial magnetic field stimulation (TMS) on the free radical production and neuronal cell loss produced by 3-nitropropionic acid in rats. The effects of 3-nitropropionic acid were evaluated by examining the following changes in: the quantity of hydroperoxides and total radical-trapping antioxidant potential (TRAP), lipid peroxidation products, protein carbonyl groups, reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px), catalase and succinate dehydrogenase (SDH) activities; total nitrite and cell death [morphological changes, quantification of neuronal loss and lactate dehydrogenase (LDH) levels]. Our results reveal that 3-nitropropionic acid induces oxidative and nitrosative stress in the striatum, prompts cell loss and also shows that TMS prevents the harmful effects induced by the acid. In conclusion, the results show the ability of TMS to modify neuronal response to 3-nitropropionic acid.

Animals↗
PubMed2004

Effect of nicotine on 3-nitropropionic acid-induced oxidative stress in synaptosomes.

In this paper, the effect of nicotine on the oxidative changes produced by 3-nitropropionic acid (20 mg/kg i.p./day for 4 days) in striatal and cortical synaptosomes of Wistar rats was studied. The effects of 3-nitropropionic acid were evaluated as changes in the quantity of protein carbonyl groups, lipid peroxidation products, superoxide distumase activity and reduced succinate dehydrogenase activity. All changes were prevented by the pre-injection of nicotine (1.5 mg/kg i.p./day), beginning 4 days before and continuing for 4 days after the first injection of 3-nitropropionic acid. These findings indicate that: (i) 3-nitropropionic acid induces a state of oxidative stress in cortical and striatal synaptosomes and (ii) nicotine prevents oxidative stress induced by 3-nitropropinonic acid. In conclusion, the results show the ability of nicotine to modify neural response to 3-nitropropionic acid with the protective mechanism likely involving the antioxidative processes of nicotine.

Animals↗
PubMed2004

Adrenalectomy and dexamethasone replacement on yawning behavior.

Yawning, a phylogenetic behavior, present in reptiles, birds and mammals, has been studied for several decades, but to date its physiological function is still unknown. The role of stress as well as several peptides and the hypothalamus has been studied in relation to its regulation. To date however, no studies has been carried out to determine the role of the adrenal glands. Therefore, yawning behavior was studied in adrenalectomized rats, who then received dexamethasone replacement. The results show that rats whose adrenal glands were removed stopped both spontaneous and apomorphine-induced yawning, while dexamethasone reverted this effect. The results are discussed in terms of the possible role of corticosterone on yawning behavior.

Adrenal Glands↗
PubMed2004

Cell transplantation for Parkinson's disease: present status.

1. Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of neurons in the substantia nigra pars compacta and a striatal deficiency of dopamine. PD typically affects people in late middle age and progresses slowly. In the early stages of the disease, treatment targeting the dopaminergic network is effective. However, with disease progression, transplantation is an option for repairing and replacing missing dopaminergic neurons. 2. In this review, we evaluate the tissue grafts and cellular therapies that have and are being considered. Clinical trials were originally derived from transplants of adrenal medullary chromaffin cells and embryonic nigral dopaminergic neurons in patients with PD. 3. Recently, novel molecular and cellular treatments are being utilized in animals and these include embryonic stem cells, fetal cells from pigs, or transfected cells. In spite of new molecular techniques and some 20 years of experience, the transplantation therapy for PD has today the same problems and results as the first reports which used neural fetal tissue or adrenal grafts.

Animals↗
PubMed2003

Olfactory dysfunction in hereditary ataxia and basal ganglia disorders.

In the present study the olfactory system of hereditary ataxia patients was tested using the smell identification test. Two previous findings suggested a possible olfactory impairment in these patients. First, an olfactory dysfunction has been found in different neurodegenerative diseases, and second, human functional imaging has shown cerebellar activation during olfaction. As an initial approach to determine if cerebellar ataxia impairs the olfactory process, cerebellar ataxia patients, along with basal ganglia patients, were tested. The results show an olfactory deficit in both basal ganglia and hereditary ataxia patients. Further exploration of the olfactory capacities in hereditary ataxia is necessary to elucidate the specific nature of the deficits.

Adult↗
PubMed2003

Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity.

Adrenal chromaffin cell (ACC) transplants, alone or combined with levodopa treatment, were used in attempted therapy for Parkinson's disease (PD). In a previous study, we demonstrated that levodopa caused chromaffin cell death either by necrosis or by apoptosis in cell culture. Here we report the beneficial effect of a water-soluble derivative of fullerene C(60) (a novel molecule with potent antioxidant properties) and of ascorbic acid when applied to chromaffin cell cultures exposed to levodopa. Both antioxidants remarkably increase the ACC survival and prevent cell death, including apoptosis. Although ACC transplants are not currently considered as an option for PD treatment, these observations should help in exploring the possibilities of preventing the neurotoxicity generated by levodopa and in envisaging new strategies for PD treatment by combining the clinical use of levodopa and potent antioxidants. Chemical properties of fullerene related to biological uses are discussed.

Animals↗
PubMed2002

Mechanisms of nicotine actions on dorsal raphe serotoninergic neurons.

Nicotine, locally administered into the dorsal raphe nucleus (DRN) of rat midbrain slices, increased the discharge rate of 70% of serotoninergic neurons, decreased it in 30% and induced reciprocal oscillatory increases in serotonin (5-hydroxytryptamine, 5-HT) and gamma-aminobutyric acid (GABA) release. All of nicotine's stimulatory effects were maximal at 2.15 microM. Bicuculline, a GABA(A) receptor antagonist, increased the firing rate in 64% of serotoninergic neurons, decreased it in 36% and augmented serotonin and GABA release. Bicuculline increased nicotine's stimulatory effects on firing rate but did not reverse the inhibitory ones. N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinil-cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist, increased the firing rate of 88% of serotoninergic neurons, as well as serotonin and GABA release and reversed nicotine's inhibitory action on serotoninergic neurons. These data suggest that nicotine decreases the firing rate of one third of serotoninergic neurons through serotonin release and increases the firing rate of the remaining two thirds, due to stronger stimulatory than indirect inhibitory effects.

Animals↗
PubMed2002

Effects of nicotine on alcohol intake in a rat model of depression.

Clinical studies suggest that depression facilitates alcohol abuse. Depressed individuals also have increased rates of smoking, and it has been suggested that nicotine may improve depression. It is therefore possible that nicotine may reduce alcohol use in depression. To investigate this potential relationship, we evaluated alcohol intake in an animal model of depression, which consists of administering clomipramine (CLI), a preferential serotonin reuptake inhibitor, to neonatal rats. This pharmacological manipulation produces adult depression-like behaviors, such as reduced aggressiveness, decreased pleasure seeking, diminished sexual activity, increased locomotor activity and increased REM sleep. In this study, we found that CLI rats exhibited significantly higher locomotor activity, lower aggressiveness and higher alcohol intake than control rats. Chronic administration of a low dose of nicotine (0.25 mg/kg/day) or a sham operation did not modify these behaviors. However, chronic administration of nicotine at a higher dose (1.5 mg/kg/day) significantly increased aggressive behavior and reduced alcohol intake in CLI rats. The effect of nicotine on alcohol intake lasted at least 1 month after cessation of nicotine administration. These results indicate that nicotine reverted some depression signs and reduced alcohol self-administration in the CLI model of depression.

Alcohol Drinking↗
PubMedDate not supplied

Effects of long-term administration of nicotine and fluoxetine on sleep in depressed patients.

BACKGROUND: The long-term effects of transdermal nicotine and fluoxetine on sleep and major depression were investigated. METHODS: Two independent groups of 12 nonsmoking patients with major depression (Hamilton Rating >/=18) served as subjects. The first group received transdermal nicotine (17.5 mg) while the second group received an oral dose of 20 mg/day of fluoxetine, 5 days weekly for 6 months, 3 days weekly at month 7 and 1 day/week at month 8. From the 9(th) to the 14(th) month, once a week a patch without nicotine and an oral placebo substituted nicotine and fluoxetine. Polysomnographic recordings were conducted and depressive symptoms evaluated at baseline and on a monthly basis during medication and during withdrawal. RESULTS: Nicotine diminished wakefulness and stage 1 and increased REM sleep latency and slow wave sleep throughout the study. A small decrease of REM sleep duration was observed upon nicotine withdrawal. Fluoxetine increased wakefulness, stage 1 duration and REM latency and decreased the sleep efficiency index. Both nicotine and fluoxetine improved mood according to HRS-D scores. CONCLUSIONS: Nicotine and fluoxetine showed equivalent antidepressant efficacy; however, important differences in sleep parameters were observed between nicotine and fluoxetine, both during their administration and following withdrawal.

Adult↗