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Biomedical subjects

M Mirmiran

Publications and source records attributed to M Mirmiran.

At least 91 records · Page 5Linked to original sources

Effects of aging and housing in an enriched environment on sleep-wake patterns in rats.

The effects of aging and housing in an enriched environment were assessed in young adult (4-7 months) and old (27-31 months) male Brown Norway rats by conducting 24-h sleep-wake recordings. Comparison of recordings made in rats of different ages, housed in a standard laboratory environment, revealed a reduction of the time spent in slow wave and desynchronized sleep during the light period in the old rats. Furthermore in the old rats, sleep was more fragmented and the amplitude of the circadian sleep-wake rhythm was reduced. In both age groups, housing in an enriched environment resulted in an increase of the time spent in slow wave and desynchronized sleep during the light period. Old "enriched" rats showed an additional alleviation of the senescence-related shortening of sleep cycles and desynchronized sleep epochs. The reduction of the circadian sleep-wake amplitude observed in old age was, however, not affected by the differential housing period. It is concluded that the similarity of the changes in sleep pattern in young and old rats after increased environmental complexity may reflect a preserved capacity of the senescent nervous system to adapt to environmental changes.

Adaptation, Biological↗

Effects of melatonin and 5-methoxytryptamine on sleep-wake patterns in the male rat.

Melatonin and 5-methoxytryptamine were administered continuously over a period of 1-3 months to adult male rats by means of subcutaneously implanted silastic capsules containing one or the other of these pineal hormones. Polygraphic recordings during several weeks following hormonal application showed an increase in the amount of time spent in both quiet and rapid eye movement sleep, during the light as well as the dark period; however, diurnal sleep-wake rhythmicity was not affected by either treatment. We conclude that pineal hormones have sleep-promoting effects, but that their correlation with the light-dark cycle does not imply that they are causal factors in generating diurnal rhythms of sleep and wakefulness.

5-Methoxytryptamine↗

Central neurotransmitter disturbances underlying developmental neurotoxicological effects.

Transmission of information among neurons is of a chemical nature. The activity of the neurotransmitter in the brain is regulated by the spontaneous activity of neurotransmitter cell body and the sensitivity of both pre- and post-synaptic receptors. Neurotransmitters are present at very early stages of brain development; they do not only mediate the behavioral-physiological responses of the immature animal, but have trophic effects on the maturation of target neurons as well. Many centrally acting drugs which are frequently used also during pregnancy for the treatment of depression, hypertension, epilepsy, asthma, insomnia, hyperkinetism and other neurological and psychiatric disorders act directly on brain neurotransmitters (in particular monoamines) and behavioral states. Chronic administration of drugs acting on monoamines (such as clonidine, imipramine, alpha-methyl-Dopa, reserpine, monoamine oxidase inhibitors, diazepam) disturb the spontaneous activity and behavioral state dependency of the monoaminergic cells, influences neurotransmitter turnover and change the sensitivity of both pre- and post-synaptic receptors. Sensory deprivation during a critical period of development is known to produce permanent effect on the brain; e.g., monocular deprivation during a particular period of development in a kitten leads to a rewiring of the connectivity in the visual system in the adult cat. Disturbances in neurotransmitter activity during early life will induce a comparable reorganization of the chemical structure of the adult brain.

Animals↗

Growth and plasticity of rat cerebral cortex after central noradrenaline depletion.

Male Wistar rats (aged 31 to 33 days) received bilateral intraventricular injections of saline or 6-hydroxydopamine and were subjected to either "standard" or "enriched" rearing conditions for 42 days. The treatment reduced cerebral cortical noradrenaline by 80% and decreased the growth of the cerebral cortex. It did not, however, prevent experience in an enriched environment from enhancing the growth of the cerebral cortex.

Animal Husbandry↗

Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment.

The effects of aging and of housing in an enriched environment on performance in an 8-arm radial maze were evaluated in young adult (7-8 months) and old (30-33 months) male Brown-Norway rats, using a procedure in which the rats were confined for 8 s to the central platform of the maze between consecutive choices. Although the old rats attained a level of performance which was clearly above change, they were shown to perform worse than the young rats. No performance differences were found between differentially housed rats of the same age group. In a second experiment recovery cycles of visual evoked potentials were determined in the same rats by using paired flashes with an interstimulus time of 400, 300, 200, or 100 ms. Recovery was consistently smaller in the old rats as compared to the young ones. No correlation could be demonstrated, however, between radial maze performance or housing condition and recovery functions of the visual evoked potentials. This finding indicates that a decline in visual sensitivity cannot readily explain the impaired radial maze performance of old rats. Evidence which suggests that age-related hippocampal changes play a major role in the radial maze performance deficit is discussed.

Age Factors↗

Effects of pontine lesions on brain stem polyneuronal activity during sleep in infant rats.

Multiple-unit activity was recorded from residual neurons in the gigantocellular field ( FTG ) of the pontine reticular formation in young rats after extensive contralateral FTG lesions. Epochs of normal appearing active sleep continued to occur but were characterized by abnormally low FTG neuronal firing rates. In contrast, during epochs of active sleep with exaggerated motility, the FTG discharge frequencies approximated those observed during active wakefulness.

Animals↗

Electrocortical activity patterns during chloral hydrate induced sleep in developing rats.

The neocortical EEG was quantified during sleep, while under light chloral hydrate anaesthesia, in rats ranging from 9 to 20 days of postnatal age. Continuous amplitude modulation at 0.5-1.0 min per cycle, synchronously over all frequency bands, was observed in 9- and in 10-day-old pups. By day 13, the mean amplitude had risen considerably in each of the frequency bands, and a slow fluctuation in delta-wave activity began to be discernible. Sodium glutamate injections induced EEG changes at 10 days which mimicked certain aspects of normal maturation (viz., large stereotyped potentials at irregular intervals, along with a selective increase in delta-wave activity). Natural as well as experimentally induced EEG changes were paralleled by a rise in neocortical amino acid concentrations, including glutamic acid and GABA. Delta wave amplitudes during quiet sleep increased still further between 13 and 14 days, while beta activity remained at a constant level. Between days 14 and 15 a precipitous decline in delta-wave activity was found, attributable to greater inhibition of slow waves during active sleep. No further developmental changes were noted, except for a gradual rise in the time spent in quiet sleep relative to active sleep.

Aging↗

Age-related changes in the sleep pattern of male adult rats.

In order to study whether or not the age-related changes in the sleep pattern observed in humans also occur in rats, young adult (4 months) and old (22 months) male Wistar rats were implanted with EEG and EMG electrodes for 24 h on-line registration by means of an automatic sleep-classifier. During the 12 h light period, the old rats as compared to the young adult ones showed a significant increase of the time spent awake and a decrease of active sleep time. Furthermore, the light-dark ratio was decreased in the old rats for wakefulness and active sleep. Off-line analysis of the EEG during quiet sleep and active sleep revealed no differences between the two age groups. These results suggest the existence of a number of considerable age-related changes in the sleep pattern of adult rats, which are comparable to those observed in humans.

Aging↗

Impaired growth of the cerebral cortex of rats treated neonatally with 6-hydroxydopamine under different environmental conditions.

Male Wistar rat pups received subcutaneous injections of either 100 mg/kg 6-hydroxydopamine (6-OHDA) or saline on days 1, 3, 5 and 7. The noradrenaline (NA) content of the cerebral cortex was reduced by 70% while sleep registration during the first two weeks of life did not show any significant differences between drug- and saline-treated animals. After weaning (day 25), both 6-OHDA- and saline-injected animals were reared under standard and enriched environmental conditions. Whereas a clear increase in cerebral cortical weight after experience with an enriched environment was found in saline-treated rats, 6-OHDA-treated animals had lower cortical weights and showed less increase due to the environment. These results demonstrate that catecholamine neurotransmission during early development influences the development and plasticity of the cerebral cortex.

Animals↗

Arousal episodes during sleep in the neonatal rat.

Hippocampal EEG and neck EMG activity were recorded in restrained as well as in unrestrained rat pups following treatment with drugs which selectively suppress wakefulness and active sleep, respectively. Chloral hydrate did not affect active sleep but eliminated the bursts of coordinated total-body movements which were seen during sleep, especially under conditions of restraint. Chlorimipramine, in contrast, suppressed active sleep while sparing the coordinated total-body motility. It is concluded that these latter movements represent an episodic arousal phenomenon, against a background of quiet sleep, which becomes intensified under certain postural conditions.

Animals↗

The environmental enrichment effect upon cortical growth is neutralized by concomitant pharmacological suppression of active sleep in female rats.

In order to examine the hypothesis that active (REM) sleep contributes to the enhanced brain development which is observed in rats reared under enriched conditions, 3 groups of female rats were assigned at 28 days after birth to either: (a) daily 2.5 h exposure to an enriched environment, followed immediately by active sleep deprivation (clonidine injection); (b) daily environmental enrichment plus vehicle only; or (c) daily vehicle injection, but continuous rearing under standard laboratory conditions. In addition, so as to control for a possible direct pharmacological effect upon cortical growth, another series of rats was chronically injected with clonidine or saline under standard conditions. At 65 days of age all the animals were sacrificed and the brains dissected into different regions for weighing. A significant increase in total brain weight (mainly due to a heavier cerebral cortex) was found in the enriched-saline group as compared with the standard-saline controls. In contrast, the enriched-clonidine rats showed no differences from the standard-saline group. Moreover, no significant differences were found between clonidine- and saline-injected rats reared in the standard environment. The results indicate that active sleep and central NA activity play a role in growth-promoting effects of environmental stimulation upon specific brain regions.

Animals↗

Pharmacological suppression of REM sleep prior to weaning counteracts the effectiveness of subsequent environmental enrichment on cortical growth in rats.

Male Wistar rat pups were deprived of REM sleep by means of daily injections of clonidine between 8 and 21 days after birth. From day 28 they were reared under either 'enriched' or 'standard' environmental conditions. At 75 days of age the animals were sacrificed, and the regional brain weights were compared with two (differentially reared) control groups. Whereas cortical weight was greater in the enriched than in the standard control rats, no differences were found between the corresponding REM sleep-deprived (i.e. clonidine-treated) groups. These results suggest that REM sleep deprivation and/or disturbances of central noradrenergic function during early development can counteract growth responses of the brain to environmental stimulation later in life.

Animals↗

Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat.

In order to test the hypothesis that active sleep (AS) is important for the normal development of the central nervous system, 3 different deprivation methods were applied to male Wistar rat pups during the first month of life. Daily injection of clomipramine from 8 to 21 days of age reduced the high level of AS to less than the adult value throughout most of the experimental period. Administration of clonidine from 8 to 21 days of life induced an almost total suppression of AS. Instrumental deprivation, using the 'pendulum' method, led to a significant (but less severe) AS reduction during 2-4 weeks of postnatal age. Open-field behavior testing in adulthood revealed a higher than normal level of ambulation in all 3 experimental groups. Masculine sexual responses were deficient, due to a low level of both mounts and ejaculations, in both clomipramine- and clonidine-treated animals. Neither passive avoidance learning nor dark preference tests revealed any differences between the experimental and control rats. Sleep observations showed that there was an abnormally high incidence of large myoclonic jerks during AS in both clomipramine- and clonidine-treated rats. Subsequent measurement of regional brain weights showed a significant reduction in the cerebral cortex and medulla oblongata, as compared with the respective control groups, in both the clomipramine- and the clonidine-treated rats. In addition, DNA and protein determination in the affected brain areas showed a proportional reduction in the cortex and in the medulla. These results demonstrate that interference with normal functioning either of AS per se or of specific monoaminergic transmitter systems during early development can produce long-lasting behavioral as well as brain morphological and biochemical abnormalities in later life.

Animals↗

Sleep patterns during rearing under different environmental conditions in juvenile rats.

Male Wistar rats were chronically implanted at weaning with electrodes for recording EEG amd EMG. From one month of age, they were randomly assigned to either 24 h or 2 h daily 'enriched' (EC), 'standard' (SC) or 'isolated' (IC) rearing conditions. The 24 h-EC group showed the following changes with respect to both the SC and the IC groups: (a) more quiet sleep time; (b) more active sleep time, and (c) shorter active sleep latency. These differences were evident by the third week of environmental conditioning, became statistically significant by 4 weeks, and continued to increase throughout the rest of the enrichment period. None of the sleep parameters showed any significant differences between the SC and the IC groups. The 2 h-EC rats showed an increase in both quiet sleep and active sleep time during the experimental period, whereas the controls showed the expected decline. Morphological investigations at 3 months of age revealed a significant weight increase in the cerebral cortex, and even more so in the hypothalamus as compared with the control group in the 2 h-EC rats.

Aging↗

Neuronal discharge patterns in the occipital cortex of developing rats during active and quiet sleep.

Spontaneous action potentials were recorded at 1 mm depth (layer IV/V) in the occipital cortex of free moving rats between 8 and 60 days of postnatal age. Neuronal firing rates during quiet sleep (QS) increased sharply around day 11-12, parallel with an increase in the amplitude of EEG slow waves. The QS discharge pattern at all ages consisted of intermittent action potentials interspersed with short bursts. Active sleep (AS) from day 11-12 was characterized by longer lasting and more frequent bursts, and by a 2-3 X higher mean neuronal discharge rate than during QS. A peculiarity in 12-day-old rats was the presence of large fluctuations in overall firing rate continuously throughout sleep. Clomipramine completely abolished AS (for several hours) at all ages studied, during which time the cortical firing rates during sleep remained at (or lower than) the QS level prior to drug injection.

Aging↗

Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: effects upon adult sleep and behavior in the rat.

In an attempt to study the possible role of active sleep in brain development, male rats were injected twice daily with chlorimipramine, a potent monoamine reuptake blocker, from 1 week to 3 weeks of postnatal age. AS was reduced to less than 10% of total sleep time, the level found in mature rats. Most of the AS reduction was compensated for by quiet sleep but a slight increase in wakefulness also occurred, owing to brief interruptions of sleep at times when AS was expected. In adulthood, the AS-deprived rats showed a higher percentage of AS than did the controls, due to an increase in frequency and duration of AS epochs. Moreover, many of the epochs contained abnormally frequent and strong jerky body movements and rapid-eye-movements, reminiscent of neonatal AS patterns. In addition, the amplitude of hippocampal theta waves during AS was greater than in control rats. The chlorimipramine-treated rats also showed behavioral abnormalities in later life. On the open field test exploratory behavior was much reduced, while increased rearing and defecation occurred. Masculine sexual performance was severely deficient, primarily due to the low level of intromissions and ejaculations. Experimental animals performed less efficiently than controls on a temporal learning task (differential reinforcement of low response rate) and responded more rapidly on a spatial task (left-right alternation learning). These results demonstrate that early interference with the functioning of monoaminergic systems can have long-lasting physiological and behavioral consequences. Furthermore, they are consistent with the hypothesis that AS is an important factor in normal brain development.

Aggression↗