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Biomedical subjects

T Desiraju

Publications and source records attributed to T Desiraju.

At least 37 records · Page 2Linked to original sources

EEG spectral power reduction and learning disability in rats exposed to lead through postnatal developing age.

The present study was carried out to assess electrophysiological and behavioral changes in Wistar rats caused by consuming a daily dose of lead acetate (400 micrograms lead/g body weight/day, given by gastric intubation, from second day of birth to 60 days of age. At 60 days of age, the lead treated rats showed in both wakeful and slow wave sleep stages, a statistically significant reduction in the delta, theta, alpha and beta band EEG spectral power in motor cortex (MC) and hippocampus (HI) with the exception of the delta and beta bands power of MC in wakeful state (WA). Lead administration was discontinued after that age for allowing rehabilitation for 40 days. Then, operant behavioral assessment was done. Results revealed that the lead treated animals took significantly more time and sessions than control normal animals in attaining criterion of learning. Hence exposure to lead in early age could result in a learning disability persisting even after discontinuation of exposure.

Animals↗

Synapses in developing cingulate and hippocampal cortices in undernourished rats.

Differential patterns of developmental changes were observed between 10 and 150 days of age in numerical densities of ethanolic-phosphotungstic acid stained synapses in the molecular layer of cingulate cortex (area 29 c,d) and hippocampus (CA1)-dentate region in rat. Chronic caloric undernutrition commencing prenatally caused considerable reduction of synaptic densities up to 45 days of age in both the cortices, but showed opposite trends subsequently; the density attained was higher than control in the cingulate area, but lower than control in hippocampus-dentate area. Post-weaning rehabilitatory nutrition resulted in a reduced deviation from normal in the cingulate area but not in the hippocampus-dentate area.

Aging↗

Oxygen consumption during pranayamic type of very slow-rate breathing.

To determine whether the yogic Ujjayi pranayamic type of breathing that involves sensory awareness and consciously controlled, extremely slow-rate breathing including at least a period of end-inspiration breath holding in each respiratory cycle would alter oxygen consumption or not, ten males with long standing experience in pranayama, and volunteering to participate in the laboratory study were assessed. These subjects aged 28-59 yr, had normal health appropriate to their age. Since kumbhak (timed breath holding) is considered as an important phase of the respiratory cycle in the pranayama, they were categorised into two groups of five each, one group practising the short kumbhak varieties of pranayama, and the other the long kumbhak varieties of pranayama. The duration of kumbhak phase was on an average 22.2 percent of the respiratory cycle in the short kumbhak group, and 50.4 per cent in the long kumbhak group. The oxygen consumption was measured in test sessions using the closed circuit method of breathing oxygen through the Benedict-Roth spirometer. Each subject was tested in several repeat sessions. Values of oxygen consumption of the period of pranayamic breathing, and of post-pranayamic breathing period, were compared to control value of oxygen consumption of the prepranayamic breathing period of each test session. The results revealed that the short kumbhak pranayamic breathing caused a statistically significant increase (52%) in the oxygen consumption (and metabolic rate) compared to the pre-pranayamic base-line period of breathing. In contrast to the above, the long kumbhak pranayamic breathing caused a statistically significant lowering (19% of the oxygen consumption (and metabolic rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increase of dendritic branching of CA3 neurons of hippocampus and self-stimulation areas in subjects experiencing self-stimulation of lateral hypothalamus and substantia nigra-ventral tegmental area.

Golgi examination of neurons of self-stimulation areas of the lateral hypothalamus and substantia nigra-ventral tegmental areas of adult Wistar rats that had experienced self-stimulation for 10 days revealed a significantly higher number of dendritic branching points in the two self-stimulation areas, and also in the hippocampus (CA3 pyramidal neurons) than in inexperienced rats.

Animals↗

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development.

Wistar rat pups were administered either a high dose of lead acetate (400 micrograms lead/g body weight/day) or a low dose (100 micrograms lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.

Animals↗

Effect of lesions of areas of brain--stimulation reward of one region of brain on operant behaviour for receiving electrical stimulation into sites of another region and on operant behaviour for food reward.

It was aimed to study the effects of lesions of a self-stimulation (SS) area of one region of brain on the SS of another region, and on feeding behaviour in adult Wistar rats (males). The two regions proposed for study were the lateral hypothalamus (LH) and the substantia nigra-ventral tegmental area (SN-VTA). The objective was to elucidate whether each region had its own neural organization for SS behaviour or not, and whether the neural substrates of SS behaviour and feeding behaviour were one, or separate. Four bipolar electrodes were implanted bilaterally in LH and SN-VTA in each rat, and their SS pedal press rates for rewarding electrical stimulations were characterised. The rats were also trained in operant conditioning paradigm for receiving reward of food grains in FR-30 schedule. Their free-field food intake in home cages was measured. Later, electrolytic lesions of the four electrode sites were made one after another at 2-day intervals through the same biopolar electrodes. After each lesioning, the SS of the same and of the other electrode sites, and the operant performance of FR-30 food reward schedule, and daily free-field food intake (in home cage) were determined. Lesions of the LH SS site always disrupted SS-of contralateral LH but not of SN-VTA SS. Lesions of SN-VTA had not modified contralateral SN-VTA SS. A study of effects of ipsilateral lesions of LH SS site on SN-VTA SS, or of lesions of SN-VTA SS site on LH SS, revealed a range of changes, as were also effects on the FR-30 operant performance and daily food intake. Medium size lesions of SS area made in one region affected the SS of that area but not usually the SS of the other region. Large lesions of one region affected the SS of the other regions also. With large lesions, feeding behaviour also was affected, firstly of the operant type and secondly the free-field type.

Animals↗

Inhibition of positively rewarding behavior by the heightened aggressive state evoked either by pain-inducing stimulus or septal lesion.

Using a footshock elicited aggression paradigm, aggressive responses were scored in normal and in septal-lesioned adult male Wistar rats. Septal lesions were made electrolytically to include the medial and lateral septal nuclei. The lesion was confirmed by behavioral criteria (septal aggression) and post-mortem histology. The aggressive response types (threat, attack) of the septal animals were compared with their corresponding age and weight matched controls. Results showed a statistically significant increase (P = 0.05) in the number of attack responses but not the threat responses in septal animals. The modulatory role of the aggressive experience on responsiveness to positively rewarding or hedonic stimuli was assessed by quantifying the intracranial self-stimulation (SS) rates that were obtained before and after an aggression schedule. For testing the SS behavior bipolar electrodes were implanted in the ventral tegmental area--substantia nigra (VTA-SN). Results showed a decrease in SS pedal press rates in post-aggression schedule as compared to the pre-aggression period in the normal subjects. This depressing effect lasted for over a week. In septal lesioned rats the SS rates were virtually abolished even without having an aggressive schedule. These experiments revealed the effect of environment and of a brain area in provoking aggressive mood and its inhibitory consequence on responding for positive experience.

Aggression↗

Comparative assessment of pedal pressing rates of self-stimulation of hypothalamus and midbrain with both square wave and sine wave stimulus parameters.

In Wistar rats, the regional differences of pedal pressing rates of self-stimulation (SS) of lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) were assessed with electrodes implanted in both regions in each subject. Average of SS rates of SN-VTA sites was significantly higher than that of LH sites, tested with both sine wave and square wave types of stimuli. There was no significant difference in SS rates between males and females, and also in the females between different days of oestrus cycles. The high rates of robust SS observed in this study relative to SS rates reported in past literature were probably due not only to the placements of electrodes in the main substrates of SS, but also to the parameters of stimulus used (0.25 sec trains of sine waves through bipolar electrodes).

Animals↗

Quantitative assessment of dendritic branching and spine densities of neurons of hippocampal embryonic tissue transplanted into juvenile neocortex.

Embryonic 18-day-old hippocampal tissue was transplanted into a fresh cavity in frontal neocortex in 18-day-old (juvenile) Wistar rats. The transplant was examined after 2-5 months. The rapid Golgi procedure was used to assess quantitatively the dendritic branching (intersections and branching orders) and spine numbers per neuronal region, and spine densities (per 20 microns segment) on the pyramidal neurons, granule neurons and other types. The results revealed that the graft neurons generally have significant deviations from those of normal native hippocampal neurons. The aberrations were present in both pyramidal and granule cells. There were also many neurons which could not be classified into the known types. The pyramidal neurons showed a significant deficiency in dendritic branching, more often in basal dendrites than in apical dendrites. Apical dendrites of the graft pyramidal neurons also developed spine densities relatively better than basal dendrites, and sometimes significantly higher than even normal neurons. The significant deficiency in spine numbers of basal dendrites was primarily due to deficiency in dendritic branching rather than to spine density. On the contrary, the granule cells developed significantly less of both dendritic branching and spine densities (hence spines per neuron) than normal hippocampal granule neurons. The unclassifiable neuronal types had generally high dendritic branching and spine densities relative to the other neurons of the graft. The study discusses the importance and necessity of making quantitative assessments of neurons to understand whether the apparently normal neurons of transplants are really normal, and how far they are deviant. So far, quantitative assessments have been seldom reported in this important area of research, hence, this study is the first of its kind to highlight it.

Animals↗

Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex.

This is a report of comparison of developmental changes of spine densities on the different categories of dendrites of neocortical pyramidal neurons (V and VI layers of motor and visual areas) of Wistar rat, during 11-150 days of age, under conditions of normal nutrition and under chronic caloric but not protein deprivation. The studied animals were of F2 generation born to parents undernourished to a degree that their weights were only 40-50% of normal control. At such a level they would be active, reproduce, and not morbid. Similar level of undernutrition also continued in the F2 group studied. A group of undernourished animals was also, for rehabilitation, put on normal diet from 21 days of age. Visual and motor cortical area pieces were impregnated by Stensaas' rapid Golgi method. Spines were counted on successive 20-micron segments (I-IV) of both apical and basal dendritic main shafts as well as primary and secondary branches. The spine count per segment (density) in the normal population reached exuberant values by 26-50 days of age and later underwent a progressive decline or pruning by 30-50% or more by 150 days of age. The degrees of exuberance and pruning varied in different categories of dendrites, generally being more conspicuous in motor than visual cortex, and more in basal than apical dendrites. Under the conditions of chronic caloric restriction, the phenomenon of exuberance was retarded and pruning was not observed. On the contrary, there was a progressive increase in the spine densities on both basal and apical dendrites, in motor and visual cortex. By 150 days of age, the spine densities were not only greater than the final counts for respective segments in the normal animal, but even greater than the exuberant counts. Postweaning caloric rehabilitation had only a modest impact against this deviation. Preliminary data (intersections) of dendritic branching also indicated a similar pattern of changes (lag followed by increase), but of a lesser degree. These alterations in neuronal development are interpreted as biological adaptations evoked in shaping the homeostasis of the organism's brain and behaviour by factors of nurture.

Aging↗

Alterations of dendritic branching and spine densities of hippocampal CA3 pyramidal neurons induced by operant conditioning in the phase of brain growth spurt.

An operant conditioning study was carried out on Wistar rat pups of brain-growth-spurt age to assess the plasticity of apical dendritic branching and the numerical spine densities of CA3 pyramidal neurons of the hippocampus. In rapid Golgi-stained material we studied the effects of operant conditioning commencing at 16 days of age and terminating on the 23rd day of age. The data of the learning group (L) were compared with those of the sham experimental control group (E) and of the control group reared under standard conditions (S). The results revealed a significant (ANOVA F test) increase in the number of branching points of the dendrites of the learning group compared with the other groups. The grand averages of spine densities also showed an overall increase in the learning group over the sham-experimental and standard groups. Segmental comparisons revealed a more interesting observation that significant changes in the spine densities of the learning and sham-experimental groups occurred in some segments of dendrites but not in all. A few segments showed moderate spine decreases also, compared with the control group. The spine differences of segments were mainly in the stalked types. Excrescences which are spines on which mossy fibers are known to synapse increased in both learning and sham-experimental groups, but not significantly (ANOVA). The dendritic branching and spines of nonmossy inputs of certain dendritic segments significantly increased after the learning experience in the hippocampus of the growing brain.

Animals↗

Differential effects of opioid peptides administered intracerebrally in loci of self-stimulation reward of lateral hypothalamus and ventral tegmental area--substantia nigra.

Leu-enkephalin, leu-enkephalinamide, ala-leu-enkephalin, met-enkephalin and dynorphin-A[1-13] were administered in microinjection into one of the self-stimulation sites of SN-VTA or MFB-LH and the electrical self-stimulation (SS) of the injected site and of the second site was recorded. The study revealed that the leu-enkephalin and the leu-enkephalinamide inhibited the SS of SN-VTA and produced no effect on the SS of MFB-LH, when administered into these sites. The MFB-LH injection, however, facilitated the SS of SN-VTA. The effect of ala-leu-enkephalin injection in MFB-LH was similar to the above, but the effect of the injection in SN-VTA was different in that it caused the facilitation of its SS and not the depression as seen with leu-enkephalin. Met-enkephalin injections in the two regions caused no direct or indirect changes of the SS of the regions. Dynorphin injection in SN-VTA facilitated its SS, like the injection of ala-leu-enk, but dynorphin injections in MFB-LH produced no effects. The results essentially demonstrate the differences in the effects of the different opioids in the reward system of the SN-VTA, and it is discussed that these differences are probably due to the preferences in the types of the receptors upon which these opioids act in the SN-VTA neuronal organisation. The results also demonstrate the major difference in the organisation of the reward substrate of the MFB-LH from that of the SN-VTA, as the effects of the opioids in the MFB-LH are markedly different or none compared to the effects in the SN-VTA.

Animals↗

Deviations in brain development due to caloric undernutrition and scope of their prevention by rehabilitation: alterations in the power spectra of the EEG of areas of the neocortex and limbic system.

Wistar rats underwent caloric undernutrition so as to produce undernourished pups (F1, both male and female), which were put on a reduced diet throughout life, causing deficits in body weight of 40-70%, and in brain weight of 14-20% by adulthood. These chronic undernourished rats were mated and their progeny (F2), which had suffered gestational and postnatal undernutrition, were undernourished, like their parents, throughout life until the moment of use in this study. At this degree of chronic undernutrition, rats do not appear to be sick or morbid, but only small-for-age, they are active and can reproduce. The computer-generated power spectra of the EEG of two neocortical areas (visual and motor) and of 3 regions of the limbic system (cingulate, hippocampus and olfactory bulb) of the chronically undernourished pups were obtained at different ages from birth to adulthood, and compared with the normal ontogenetic patterns of corresponding areas obtained from age-matched controls. In another group of rats, the undernutrition was imposed on normal pups from the day of weaning (21st day), i.e., after the major part of the brain growth spurt is over. Finally, the effect of restituting normal rehabilitatory nutrition from the day of weaning on the chronic group was also studied. The results show that all brain regions studied were affected by the chronic caloric undernutrition. The deviations from the normal consist of: (1) an initial lag or delay in the development of the EEG amplitude and activity by several days, (2) a later development of an abnormally high amplitude or power in the EEG power spectra by about the weaning age, and (3) an imbalance in the occurrence of the characteristics of the EEG of the respective areas of the brain (the low and high frequency spindles of slow sleep, the slow and fast theta activities of paradoxical sleep of the hippocampus, the delta rhythm, etc.). While the chronic undernutrition was continuing there was also a certain degree of spontaneous reduction in the magnitude of abnormality after about 80 days of age, instead of worsening with age, perhaps due to an intrinsic adaptational readjustment to the stress of the nutritional deprivation. The results reveal a variation in the susceptibility of development to these abnormalities. Typical examples of the range of variation of the effects are presented in the results showing that there can be nearly normal EEG patterns in some undernourished subjects (about 14-22%), and also that there can be abnormal EEG power spectra in a proportion of normals (up to about 20%).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Electrophysiology of the frontal granular cortex. III. The cingulate-prefrontal relation in primate.

An investigation of the nature of laminar potentials and impulse discharges of units of dorsolateral prefrontal cortex (FC) evoked by stimulations of cingulate gyrus was made in rhesus monkey. Anterior cingulate stimulations evoked 1.0--1.5 msec latency waves, positive on pial surface and negative at FC depths of about 500--2000 mum with about the same time scale. Following the positive wave there was also a negative wave response. The amplitude and duration of the surface positive wave and negative wave of response varied according to the state of background EEG of the area. During steady EEG the positive wave was well developed and the negative wave was incipient but during EEG oscillations, the positive wave was markedly diminished and the negative wave enlarged. The alteration of responsiveness was also confirmed in depths by changes of reversed polarity potentials corresponding temporally to surface potentials. Discrete responses of FC were evoked at stimulus frequencies of up to 20 Hz. Higher frequencies resulted in depression of responsiveness. Alternate responses were depressed between 20 and 40 Hz and all responses were progressively depressed with still higher frequencies. Impulse discharges of FC units were evoked either singly or in bursts by the cingulate stimulations. Single impulse responses were commonly found. Presumably monosynaptic responses were in the latency range of 1.2-3.0 msec. They were found at depths of about 500 mum and 1000 mum. Long latency (7 msec) responses were also observed in the upper levels of cortex. The latency of the unitary response of a multi-impulse burst was in the range of 6.5-16 msec and the frequency of impulses in burst was in the order of 500-750 Hz. Such burst responses occurred on the declining phase of the depth negative wave evoked by the cingulate stimulation. The anterior cingulate effects were found to be distributed on the prefrontal cortex from arcuate sulcus to two-thirds distance rostrally. The unit responses were more commonly found in laminae between 0.4 and 1.0 mm depth than at other depths. The cingulate effects on FC were not affected by lesion of nucleus medialis dorsalis thalami or by ablation of the pre-motor cortex. The study discloses a basis by which functional states of limbic cortex can powerfully modulate the functioning of prefrontal neocortex of primate.

Animals↗