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Biomedical subjects

R Drucker-Colín

Publications and source records attributed to R Drucker-Colín.

At least 55 records · Page 3Linked to original sources

Cerebrospinal fluid (CSF) extracted immediately after REM sleep deprivation prevents REM rebound and contains vasoactive intestinal peptide (VIP).

Intraventricular administration of cerebrospinal fluid (CSF) obtained from sleep deprived (SD) animals and vasoactive intestinal peptide (VIP) have been shown to increase rapid eye movement (REM) sleep. It has thus been suggested that VIP may accumulate in the CSF as a consequence of waking, and might thus be partly responsible for the subsequent rebound of REM sleep which follows prolonged wakefulness. To this data there are no studies testing this hypothesis. The purpose of this study, therefore, was to determine REM rebound following the extraction of CSF immediately after REMSD and to quantify by radioimmunoassay (RIA) the concentration of VIP in the CSF of progressively increasing REMSD periods. The results showed that REM rebound normally seen following REMSD is reduced by extraction of CSF, and that VIP concentration in such CSF is augmented. The results are discussed in terms of the possibility that waking induces an accumulation of VIP in the CSF, which is in turn involved in the production of REM sleep.

Animals↗

2-Deoxyglucose autoradiographic evidence that fetal substantia nigra grafts exert contralateral effects in 6-hydroxydopamine-lesioned animals who recover motor asymmetries.

Fetal substantia nigra grafts decrease turning behavior induced by dopaminergic agonists in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal system. The purpose of this study was to determine, through the [14C]2-Deoxyglucose autoradiographic method, whether substantia nigra grafts have an effect on efferent striatal nuclei and other related structures. The results showed an unexpected enhancement of metabolic activity in the substantia nigra pars reticulata and striatum on the side contralateral to the lesion and a bilateral enhancement in the thalamus and frontoparietal cortex, in rats bearing fetal substantia nigra grafts. The results are discussed in terms of the possibility that recovery of turning behavior may in part be caused by an increased activity of the striatum contralateral to the grafted side.

Analysis of Variance↗

Chloramphenicol prevents carbachol-induced REM sleep in cats.

Twenty-four cats were implanted for chronic sleep recordings. One week after the surgery, cats were divided into four groups. Two groups were treated with three i.p. injections of 150 mg/kg chloramphenicol (CAP) separated by 12 h. Carbachol (8 micrograms/1 microliter) or saline (1 microliter) was injected into the pontine reticular formation (PRF) 1 h after the last injection of CAP. The other two groups received saline or carbachol into the PRF without CAP pre-treatment. Polygraphic recordings were started immediately after the microinjection and lasted 11 h. Carbachol increased REM sleep (P < 0.001) and reduced SWS2 (P < 0.05). In contrast, chloramphenicol reduced REM sleep (P < 0.001) and increased SWS2 (P < 0.01). The combination of these drugs increased wakefulness (P < 0.01) and reduced both SWS2 and REM sleep (P < 0.001). This data shows that chloramphenicol prevents carbachol induced REM sleep. Results are discussed in terms of an interaction between brain proteins and the cholinergic system to induce REM.

Animals↗

Reduction of motor impairment by adrenal medulla transplants in aged rats.

Recently we have reported that drugs that enhance dopaminergic transmission, such as L-dopa and D-amphetamine, substantially improve the age-related deterioration of extrapyramidal motor functions, as assessed by the narrow uphill beam test. Here we report the effect of fetal adrenal medullary transplants upon the motor performance of aged rats in such a test. Rats were grafted with 300,000 cultured adrenal medullary cells, placed into the head of either the left caudate nucleus, or into both caudates. A third group was grafted with one freshly dissected adrenal medulla placed as a block of tissue into the lateral ventricle, whereas the control group sustained sham grafting. Evaluation of the motor performance of cultured and sham-grafted rats showed no improvement along the testing phase. Only adrenal block-grafted rats exhibited a significant recovery of motor coordination. Histologically, cultured cell grafts had a deteriorated appearance with poor survival rates, while block grafts exhibited chromaffin cells with round and neuron-like shapes. The results suggest that cultured adrenal grafts may not induce motor improvement due to their extremely low survival and poor integration, at least in the aged host brain, while fresh adrenal transplants may improve motor coordination for as long as 84 days.

Adrenal Medulla↗

Effects of catecholaminergic depletion of the amygdala and insular cortex on the potentiation of odor by taste aversions.

This experiment examined the effects of catecholamine depletion of the amygdala or insular cortex on the acquisition of olfactory and gustatory learning tasks. Bilateral lesions with 6-hydroxydopamine (4 micrograms/0.5 microliters) were done in either amygdala or insular cortex of Wistar male rats, with two groups receiving sham lesions. All four groups of animals were trained and tested in the potentiation of odor by taste aversion paradigm. The results showed that the amygdala-lesioned group acquired the taste, but not hte odor aversion, while the insular cortex-lesioned group acquired odor, but not taste aversion. Both sham groups showed strong taste and odor aversions. Catecholamine levels in both lesioned groups were significantly lower than those in the sham groups. These results suggest that catecholamines are necessary in the insular cortex for the acquisition of taste and in the amygdala for the acquisition of odor aversion in the potentiation of odor by taste aversion paradigm.

Amygdala↗

The combination of VIP and atropine induces REM sleep in cats rendered insomniac by PCPA.

Twenty-four cats were implanted with electrodes for chronic sleep recordings. One week after the surgery, cats were treated with two intraperitoneal injections of parachlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, to induce insomnia. Twenty-four hours after the second injection of PCPA, cats were at the peak of insomnia (strong reduction of both slow wave sleep 2 and rapid-eye movement [REM] sleep). During this period cats were divided into four groups (n = 6) and were injected with either atropine (0.5 mg/kg, IM [3.5 mmol/kg]), vasoactive intestinal peptide (VIP) (200 ng, ICV [60 pmol]) or atropine plus VIP (same doses and routes of administration). The control group received saline intramuscularly (IM) intracerebroventricularly and (ICV). Results showed that VIP and atropine injected alone and in combination increased mean total time of REM sleep in PCPA-treated animals. These findings are discussed in terms of a serotonin-acetylcholine interaction.

Animals↗

Morphological and functional development of the suprachiasmatic nucleus in transplanted fetal hypothalamus.

The development of the suprachiasmatic nucleus (SCN) in fetal rat hypothalamus transplanted to the adult brain was studied using morphological and functional methods. Anterior hypothalamic tissue was transplanted into the third ventricle, lateral ventricle or subarachnoid space of intact, adult hosts from E17 fetuses. These transplants developed the cytoarchitectonic and immunohistochemical staining characteristics of SCN, clusters of parvocellular neurons expressing vasopressin- and vasoactive intestinal polypeptide-like immunoreactivity in adjacent cellular populations, irrespective of the exact location of the transplanted tissue in the host brain. The functional status of the transplants placed in the rostral third ventricle and the foramen of Monroe was analyzed and compared to host SCN using in vitro recording of neuronal firing rate and measurement of metabolism using the 2-deoxyglucose (2-DG) technique. During subjective day, neuronal firing rates and 2-DG uptake were high in discrete cell groups within the transplants which were subsequently demonstrated to exhibit the cytoarchitectonic and immunohistochemical characteristics of SCN. The firing rates and 2-DG uptake in these areas were lower during the subjective night. This pattern of activity closely resembles that of the intact SCN. In contrast, neither transplanted anterior hypothalamic area, lacking an identifiable SCN-like structure, nor posterior hypothalamic area showed day-night differences in firing rate or 2-DG uptake. These observations indicate that SCN transplanted into intact adult hosts exhibits morphological and functional differentiation nearly identical to the host and that the transplanted SCN maintains circadian function which is probably entrained to the host SCN.

Action Potentials↗

c-fos proto-oncogene changes in relation to REM sleep duration.

Auditory stimulation has been shown to increase REM sleep periods in cats and humans. This effect has been attributed to an elevation of the level of excitability in a variety of brain stem neuronal groups. Fos-like immunostaining (FLI) has been useful in constructing maps of post-synaptic neuronal activity with single cell resolution, and has been suggested to be tightly correlated with ongoing neuronal activity. This study used FLI to quantify neurons from structures expressing c-fos in brain stem areas in animals with normal REMs and compared them with those showing extended REM periods. The results basically indicated that brain stem areas which in other studies have been described as having REM-ON cells, showed an increase in FLI, while no FLI changes occurred in areas described as having REM-OFF cells. These results are discussed in terms of the possibility that REM maintenance is related to a widespread increase in brain stem excitability.

Acoustic Stimulation↗

Behavioral and morphological studies of fetal neural transplants into SCN-lesioned rats.

We have studied the effects of fetal neuronal grafts on the temporal pattern of drinking behavior of suprachiasmatic nuclei (SCN)-lesioned adult rats. Additionally, in an independent set of animals, the immunohistochemical staining for vasopressin, vasoactive intestinal polypeptide, and neuropeptide Y and the retinal connections to the hypothalamus were studied. The behavioral experiments indicate that anterior hypothalamic transplants induced reorganization of the temporal pattern of drinking behavior when placed in the third ventricle of adult hosts bearing complete SCN lesions, but not when placed in a cavity in the occipital cortex. Such rhythmicity persists only when the animals were recorded under constant darkness but not under constant light, indicating that the restored rhythmicity was generated endogenously but that the oscillator was extremely sensitive to light. Fetal occipital cortex induced reorganization of the temporal pattern of previously arrhythmic hosts, but it disappeared when the animals were recorded under constant light or constant darkness. It is clear that this rhythmicity was exogenous. In contrast to the cortical transplants, the hypothalamic transplants showed a morphological organization similar to that found in the normal hypothalamus regardless of their placement in the host brain. From these observations it is concluded that development of neocortex is more affected by environmental factors than that of the hypothalamus. Both hypothalamic and cortical transplants induced sprouting of retinal fibers into the anterior hypothalamus and the grafted tissue. It is possible that such fibers could be the neuroanatomical substrate by which rhythmicity is induced by cortical tissue.

Animals↗

[Treatment of congenital facial paralysis with crossed innervation of facial nerve and electric field stimulation].

Congenital facial palsy is a devastating deformity. At present time there are no reports of the early treatment of this disorder. The treatment may be to supply contralateral auto reinnervation to the affected muscles through a sural-facial nerve graft enhanced by electric field stimulation. The purpose of this paper is to report 5 cases of congenital facial palsy treated by a crossed sural-facial nerve graft, enhanced by electric field stimulation. One year after surgery, clinical and electrodiagnostic examinations indicate appropriate reinnervation activity in all the patients.

Combined Modality Therapy↗

Ontogeny of the electrophysiological activity of dopaminergic cells with special reference to the influence of adrenal medullary grafts on aging.

A variety of neurological impairments during aging involves pathological changes in the basal ganglia, with the consequent deterioration of motor activities. The purpose of this study was to determine whether the extracellular activity of dopaminergic cells of the substantia nigra pars compacta of Wistar rats changes with age, and if so whether ventricular adrenal medullary grafts can influence the electrophysiological activity of the oldest age group. The results indicate that there is a significant decrease in the firing frequency of substantia nigra cells which begins at 18 months of age and is most prominent by 22-24 months of age. The rate of firing was improved with adrenal medulla grafts placed in the lateral ventricle. In addition, it was also observed that with age there is an increase in the number of cells which fire at slower frequencies. Quinpirole administration induced a significant decrease in firing frequency in all age groups, including the grafted animals. These results suggest that in the aged Wistar rats there is an impairment in the response of SNC cells, which can be partially restored by fetal adrenal medullary grafts.

Action Potentials↗

A new motor test sensitive to aging and dopaminergic function.

Neurodegenerative disorders which involve motor impairment is characteristic of old age. Although there are a few tests which attempt to assess motor incapacities, many have utilized scales which have either a great deal of subjective evaluations or are subject to learning-performance complexities. This study describes a method able to measure motor impairment of aging rats which is subject to dopaminergic influences and has negligible practice effects. The test is designed so that rats have to traverse 2 meter beams of 15 degrees inclination whose widths 3, 6, 12, 18 and 24 mm are changed on each test session using a table of random numbers. The time ceiling allowed for traversing the 2 m beams was established at 120 sec. 3-month-old rats (n = 20) and aged rats (n = 20) with a mean age of 26.5 +/- 3.8 months ranging from 23 to 34 months were utilized in this study. All young rats traversed the beams, independently of beam width, while virtually none of the old rats traversed the 3 and 6 mm beams. However, as the beam width increased more and more aged rats ascended the beam. Nevertheless, there were always a few old rats who were unable to cross even on the widest beam. When young rats were fitted with a lead belt which increased their body weight by approximately 40%, they still traversed all beam widths. On the other hand, haloperidol (0.1 and 0.2 mg/kg) severely impaired the performance of young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Dibutyryl cAMP stimulates analgesia in rats bearing a ventricular adrenal medulla transplant.

In the present study, a significant increase in pain threshold (current to elicit vocalization to tail shock) was found 15 and 60 min after injection of dibutyryl cyclic AMP (db cAMP) (30 micrograms) into the lateral ventricle in rats bearing a transplant of fetal adrenal medulla (AM). By contrast, no effect on pain threshold was observed in rats bearing an AM transplant but receiving no db cAMP, or in rats receiving db cAMP but not bearing an AM transplant. In primary cultures of rat fetal chromaffin cells, db cAMP increased the number of neuron-like cells that showed both vasoactive intestinal polypeptide (VIP)- and tyrosine hydroxylase (TH)-like immunoreactivity. These findings indicate that db cAMP exerts a pharmacological modulation of the functional activity (i.e. elevation in pain thresholds) of fetal adrenal AM transplants, and induces phenotypic changes in cultured chromaffin cells with expression of a peptide that elevates pain threshold.

Adrenal Medulla↗

Chloramphenicol modifies benzodiazepine receptor rhythm in the pontomesencephalic formation of the rat.

Pontomesencephalic benzodiazepine (BZ) receptors were measured at 4 h intervals throughout a 24 h day, and compared with those in frontal cortex, using [3H]diazepam binding. Animals were treated with saline, chloramphenicol (CAP) or thiamphenicol (TAP). An ultradian rhythm of receptors was observed in both cases, which was abolished by CAP but not by TAP. Saturation curves and Scatchard analysis indicated decreased binding was due to a decrease in the number of receptors. CAP effect on REM sleep, could be mediated by a general decrease of neurotransmitter receptors at precise periods of the wake-sleep rhythm.

Animals↗

Chronic administration of amphetamine increases glutamic acid decarboxylase activity in the rat substantia nigra.

The glutamate decarboxylase activity in the rat cerebellum, frontal cerebral cortex, hypothalamus, substantia nigra and nucleus caudatus, was measured after either acute or chronic administration of (+)-amphetamine (1.35 and 5.4 mg/kg, i.p.). It was found that following 45 days of treatment the highest dose of the drug induced a selective increase of glutamate decarboxylase activity in the substantia nigra. Also in addition to the known changes in body weight, behavior and food-intake, some of the rats (5 out of 80 rats) treated with the highest dose of (+)-amphetamine developed a self-mutilating behavior. These results suggest that after the repeated administration of a high dose of (+)-amphetamine the activity of the striatonigral GABAergic pathway is increased and supports the idea that gamma-aminobutyric acid output neurons might convey dopamine-related functions.

Amphetamines↗

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↗

REM sleep enhancement induced by sensory stimulation is prevented by kainic acid lesion of the pontine reticular formation.

It has been shown that auditory or somatic stimulation during rapid eye movement (REM) sleep is capable of producing a significant increase in ponto-geniculo-occipital (PGO) spike density as well as in REM sleep duration. The purpose of this study was to determine the role of the medial pontine reticular formation (PRF) in mediating such increase of REM sleep duration. After a baseline recording whereby on the same recording day the control and the stimulus (auditory or somatic) alternated with each REM, a group of cats was lesioned with kainic acid in the PRF. The sleep-wake cycle was recorded again on days 15, 30 and 45 post-lesion, following the same procedure. The results showed no changes in REM sleep duration and PGO spike density in the lesioned animals. However, when sensory stimulation was applied it was ineffective in producing REM sleep enhancement, although it was able to increase PGO spike density. These findings suggest that the effects of sensory stimulation on REM sleep duration are accomplished through the PRF, probably by inducing an increase in the excitability levels of such neurons, and further suggests that PGO spike density and REM duration are independent of each other.

Acoustic Stimulation↗