Biomedical subjects

T R Raju

Publications and source records attributed to T R Raju.

At least 55 records · Page 3Linked to original sources

PubMed1997

Developmental expression of synaptophysin, synapsin I and syntaxin in the rat retina.

Expression of synaptophysin, synapsin I and syntaxin was studied immunocytochemically in the developing rat retina using indirect immunoperoxidase technique. In the inner plexiform layer (IPL), syntaxin immunoreactivity appeared at postnatal day 1 (P1) whereas synaptophysin and synapsin I staining were first observed at P2. In the outer plexiform layer (OPL), synaptophysin appeared at P4, while synapsin I and syntaxin appeared at P8. In the case of synaptophysin, a punctate pattern of staining was observed from the time of its appearance (P4) in the OPL and from P12 onwards in the IPL. Synapsin I and syntaxin immunoreactivity in the OPL were of a low intensity throughout the development and in the adult stage. These findings are discussed in relation to synaptogenesis in the rat retina.

Animals↗

PubMed1997

Selective reduction of monoamine oxidase A and B in the frontal cortex of subordinate rats.

We have previously shown that subordination causes a reduction in the levels of 5-hydroxytryptamine and dopamine selectively in the frontal cortex [6]. These monoamines are catabolised mainly by the enzyme monoamine oxidase (MAO) which exists in two isoforms; MAO-A and MAO-B. The present study was carried out to determine whether there is any change in the activity of these two iso-enzymes induced by subordination and if any such alteration is confined to the frontal cortex. The animal model of dominance-subordination used was a worker-parasite paradigm in male Wistar rats. The enzyme activities were measured in five brain regions, the frontal cortex, entorhinal cortex, hippocampus, hypothalamus and striatum, using kynuramine as the substrate. Clorgyline and L-deprenyl were used in vitro to block the activities of MAO-A and MAO-B, respectively. There was a significant (P < 0.001) reduction in the activity of MAO-A as well as MAO-B selectively in the frontal cortex of the subordinate animals. This finding may suggest a reduced neurotransmitter turnover in the serotonergic and dopaminergic neurons terminating in the frontal cortex.

Animals↗

PubMed1997

An isocratic assay for norepinephrine, dopamine, and 5-hydroxytryptamine using their native fluorescence by high-performance liquid chromatography with fluorescence detection in discrete brain areas of rat.

A rapid and simple isocratic chromatographic procedure for simultaneous determination of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) using their native fluorescence by high-performance liquid chromatography coupled to fluorescence detection (HPLC-FD) is described. Since the present procedure does not involve sample prepurification, the recovery of monoamines was more than 97% (n = 12) and within a given run, coefficient of variation was less than 3.1% (n = 12). Accordingly, use of an internal standard is not mandatory. In a single chromatographic run, levels of NE, DA, and 5-HT can be determined in less than 30 min. The minimum concentration of monoamines which could be detected by this method was found to be 250 pg for NE and DA and 100 pg for 5-HT. The validity of the method was confirmed by the estimation of levels of monoamines in the hypothalamus and striatum of rat brain following treatment with clorgyline, a monoamine oxidase inhibitor.

Amines↗

PubMed1997

Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats.

30-Day-old male Wistar rats were tested for acquisition and retention of operant conditioned behavior after bilateral subicular lesions made either electrolytically or chemically (ibotenic acid). The acquisition of operant learning was carried out in lesioned rats by assessing the number of sessions required to learn the operant task, whereas the retention test was performed after lesions by assessing performance on a previously learnt operant task. The acquisition of pedal press operant learning was significantly delayed in both types of lesioned rats, without any impairment in the retention of the previously learned task after lesioning. In these animals the cell densities were quantified in cresyl violet-stained sections in different subfields of hippocampus. Following the lesion of subiculum, selective degeneration of CA1 cells without the involvement of other hippocampal subfields was observed. This might be due to the loss of target area (subiculum) through which hippocampus is connected with neocortical and subcortical structures. This, in turn, might have resulted in behavioral deficits. The data suggest that the subiculum might be involved in the acquisition of new information rather than in retention.

Animals↗

PubMed1997

Regeneration of the olfactory tract following neonatal lesion in rats.

Neuronal regeneration following early postnatal olfactory tract transection (OTS) was investigated in newborn Wistar rats. Olfactory tract lesioned rats were sacrificed at different time periods and the brains processed for Nissl staining. This was used to study the neural cell architecture; fiber tracts (myelinated fibers) were examined with Luxol Fast Blue staining. In addition, a neuronal tracing technique (i.e., retrograde labeling) was employed to study the reestablishment of connections with the target sites following transection of the tract. Degeneration of the olfactory tract was evident at the 7th day following lesion. Regeneration of the tract was not apparent even up to 60 days following transection. However, by 240 days, the olfactory tract had regenerated and the tract fibers had reestablished connection. This was confirmed by retrograde labeling of mitral cells of the olfactory bulb with Fast Blue (FB) injected into the piriform cortex, the target site of these neurons. In this study, we show that mammalian olfactory tract can regenerate spontaneously if the olfactory tract is lesioned neonatally. The results suggest that the olfactory tract is an excellent model to investigate some issues related to central nervous system regeneration.

Amidines↗

PubMed1997

Cholinergic and GABAergic modulation of self-stimulation of lateral hypothalamus and ventral tegmentum: effects of carbachol, atropine, bicuculline, and picrotoxin.

This study aimed at investigating the effects of modulators of acetylcholine-muscarinic (ACh-M) and GABAA.B-receptors in the lateral hypothalamus and ventral tegmentum on the electrical self-stimulation evoked from these regions. In each Wistar rat, a bipolar electrode and an ipsilateral insulated cannula-cum-electrode were implanted chronically in the right hemisphere. There were two placement combinations: 1. Bipolar electrode in lateral hypothalamus-medial forebrain bundle (LH-MFB) and cannulacum-electrode in ventral tegmental area-substantia nigra (VTA-SN) or 2, bipolar electrode in VTA-SN and cannula-cum-electrode in LH-MFB. The stimulation parameters were kept at a level to obtain 50% of the maximum possible asymptotic intracranial self-stimulation (ICSS) rates (M50) from each site. Carbachol injected into VTA-SN increased the ICSS responding rate of VTA-SN as well as, indirectly, that of LH-MFB, and atropine injections had an opposite effect. Similar injections of these ligands into LH-MFB again had facilitatory and inhibitory effects on its ICSS: however, there was no indirect effect on the ICSS of VTA-SN. Bicuculline injection into VTA-SN had no effect on either its ICSS or that of LH-MFB. On the other hand, bicuculline injected into LH-MFB decreased its ICSS and, indirectly, the ICSS of VTA-SN in a dose-dependent manner. In contrast, intra VTA-SN injections of picrotoxin decreased its ICSS and, indirectly, ICSS of LH-MFB. Similar injections into LH-MFB had no effect on the ICSS of VTA-SN. The results suggest that ICSS of VTA-SN is Ach-M receptor mediated and, also, this mediation influences the ICSS of LH-MFB. On the contrary, changes in ICSS of LH-MFB following Ach-M receptor ligands do not influence the ICSS of VTA-SN. The direct effects of GABA-receptor antagonists have shown disassociation because ICSS of LH-MFB was more sensitive to bicuculline, whereas the ICSS of VTA-SN was more sensitive to picrotoxin. Thus, the cholinergic and GABAergic mechanisms of the self-stimulation of lateral hypothalamus and ventral tegmentum are different.

Animals↗

PubMed1997

Effects of microinjections of cholecystokinin and neurotensin into lateral hypothalamus and ventral mesencephalon on intracranial self-stimulation.

Changes in intracranial self-stimulation (ICSS) evoked from ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) before and after microinjections of sulfated cholecystokinin octapeptide (CCK-8S) and unsulfated cholecystokinin (CCK-8US), neurotensin tridecapeptide ([D-Tyr11]NT(1-13) or [DTrp11]NT(1-13)) into either VTA-SN or LH-MFB were assessed. The current intensity was fixed at a level to obtain 60-70% of the maximal asymptotic rate. CCK-8S (0.10 microg/0.5 microl and 0.25 microg/0.5 microl) into VTA-SN resulted in dose-dependent decreases in VTA-SN ICSS of 38-42% and 78-92%, respectively, without affecting the ICSS of LH-MFB. Similar doses of CCK-8S injected into LH-MFB changed neither LH-MFB ICSS nor VTA-SN ICSS. CCK-8Us injected into VTA-SN or LH-MFB had no effect on ICSS in either site. Intra-VTA-SN injections of the neurotensin-1 (NT1) receptor agonist [DTyr11]NT(1-13) and the NT1 receptor antagonist [D-Trp11]NT(1-13) at doses of 5 microg/0.5 microl and 10 microg/0.5 microl decreased VTA-SN ICSS. NT1 receptor agonist and antagonist injections did not alter LH-MFB ICSS in any significant manner. Similar injections of these peptides into LH-MFB did not change the responding rates for LH-MFB ICSS or VTA-SN ICSS. Increasing the current intensity reversed the inhibitory effect of CCK-8S and [D-Trp11]NT(1-13) on VTA-SN ICSS and restored basal preinjection rates of responding. These results suggest that CCK(A) and NT1 receptor mechanisms in the ventral tegmentum in association with dopamine neurotransmission may be important in mediating the rewarding effects of VTA-SN ICSS but not LH-MFB ICSS.

Animals↗

PubMed1997

Dopamine receptor sub-types involvement in nucleus accumbens and ventral tegmentum but not in medial prefrontal cortex: on self-stimulation of lateral hypothalamus and ventral mesencephalon.

The involvement of different sub-types of dopamine receptors in the electrical self-stimulation behaviour was investigated using DA receptor subtype specific agonists viz R(+) SKF 38393 and LY 171555 (quinipirole). Rats were chronically implanted with bipolar electrodes in lateral hypothalamus-medial forebrain bundles (LH-MFB) and ventral tegmental area-substantia nigra (VTA-SN) or guide cannula in nucleus accumbens (nACB) or medial prefrontal cortex (mPFRCx) or cannula-cum-electrode in VTA-SN. Combining these, it was possible to inject a given receptor ligand in either nACB or mPFRCx or VTA-SN and assess the changes in intracranial self-stimulation (ICSS) of LH-MFB or VTA-SN. The experimental subjects were trained to press a pedal to obtain 0.25 s trains of cathodal rectangular pulses of 0.1 ms pulse duration (for LH-MFB electrode) or 0.3 ms pulse duration (for VTA-SN electrode). The rate-frequency curve for each subject and each placement were obtained in order to determine M50 (50% of maximum asymptotic response rate). Microinjection of SKF 38393 (a D1 agonist) or LY 171555 (a D2 agonist) into nACB caused facilitatory and suppressive effects on the ICSS of VTA-SN and LH-MFB respectively. On the contrary, intra VTA-SN injection of 10 micrograms/0.5 microliter of SKF 38393 or of LY 171555, reduced its ICSS to half as compared to vehicle injections. Under the effect of these injections, there was no change in the ICSS of LH-MFB. The combined administration of SKF 38393 (5 micrograms) and LY 171555 (10 micrograms) into nACB produced suppression of ICSS of VTA-SN to greater extent than the LY 171555 (10 micrograms/0.5 microliter). This indicates that coactivation of D1 and D2 leads to suppression of ICSS of VTA-SN. The activation of D1 receptors in nACB facilitates the ICSS of both VTA-SN and LH-MFB by increasing the reinforcement and/locomotor activity, while the activation of D2 receptors in it has opposite effect. The coactivation of D1 and D2 receptors in VTA-SN leads to the suppression of ICSS of both VTA-SN and LH-MFB. Similar injections of these receptor ligands into mPFRCx did not alter the ICSS of either LH-MFB or VTA-SN. The pre- or post-synaptic DA receptors of mPFRCx do not appear to influence the ICSS of either VTA-SN or LH-MFB in any significant manner.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Levels of dopamine and noradrenaline in the developing of retina--effect of light deprivation.

The effect of light deprivation on the levels of dopamine and noradrenaline was studied in the developing rat retina. These transmitters were estimated in three groups of rats: (i) cycling light reared; (ii) dark reared since birth; and (iii) dark reared since birth, but exposed to cycling light for 1 day prior to the estimation of catecholamines. Our results show that (1) there is a progressive decrease in the levels of dopamine and noradrenaline in the cycling light and dark reared rats during postnatal development; (2) dark rearing further reduces the content of dopamine and noradrenaline; and (3) restoration of physiological (light) stimulus in the dark-reared rats during the early postnatal period results in the recovery of noradrenaline to a greater extent than that of dopamine. This study demonstrates a progressive decrease in the plasticity of dopaminergic system during retinal development, while such a decrease is not apparent in the noradrenergic system.

Animals↗

PubMed1997

A study of structure of phenomenology of consciousness in meditative and non-meditative states.

Twelve senior Kundalini (Chakra) meditators were assessed during meditation session and non-meditation or control session using Phenomenology of Consciousness Inventory. The data has been analyzed using structural analysis to measure the altered state of consciousness and the identity state by comparing meditative state with non-meditative state. The structural analysis of pattern of consciousness during the meditative state revealed altered experience in perception (percentile rank PR = 90), meaning (PR = 82) and time sense (PR = 87), while positive affect dimension showed increased joy (PR = 73) and love (PR = 67). The imagery vividness (PR = 72), self-awareness (PR = 77), rationality (PR = 73) and arousal (PR = 69) were found to be structurally different from the ordinary state. With regards to identity state meditative experience was found to produce statistically significant changes in terms of intensity in meaning (P < 0.05), time sense (P < 0.05), joy (P < 0.05), love (P < 0.05) and state of awareness (P < 0.01). Our results indicate that long term practice of meditation appears to produce structural as well as intensity changes in phenomenological experiences of consciousness.

Adult↗

PubMed1996

(-) deprenyl attenuates aluminium induced neurotoxicity in primary cortical cultures.

The role of (-) deprenyl in offering neuroprotection to cortical neurons exposed to Aluminium chloride (AlCl3) was examined. Primary cortical cultures derived from newborn rats were exposed to AlCl3 on 6th day in vitro, at 100,200,400,600,800 and 1000 microM concentrations of AlCl3. After 48 h of AlCl3 exposure, many nerve cell bodies were swollen; a beading of neurites and a disruption of the neuritic network were also observed suggesting neurodegeneration. Lactate dehydrogenase (LDH) efflux increased in a dose-dependent manner (59-120%). (-) Deprenyl co-exposure at concentrations of 10(-7), 10(-8) and 10(-9) M significantly attenuated both the morphological alterations and the LDH efflux induced by AlCl3. This in vitro study has demonstrated that (-) deprenyl can protect neurons from aluminium induced neurotoxicity.

Aluminum Chloride↗

PubMed1996

Comparison of intracranial self-stimulation evoked from lateral hypothalamus and ventral tegmentum: analysis based on stimulation parameters and behavioural response characteristics.

The comparison of intracranial self-stimulation (ICSS) derived across the anteroposterior axis of medial forebrain bundle (MFB) from the anterior border of lateral hypothalamus (LH) to the ventral mesencephalon including ventral tegmental area-substantia nigra (VTA-SN) in Wistar rats was assessed through stimulation parameters and behavioural response characteristics. The interpretation of response rate/charge consumption (muC/min) with respect to rectangular wave and sine wave electrical stimulation parameters suggests that the rectangular wave parameters are better in order to get the maximum responding rates. The most vigorous and robust responding was observed in the VTA or VTA-SN boundary placements, followed by placements in medial sector of LH. The acquisition of ICSS was fastest in the case of VTA-stimulation. The next site with respect to rapidity of ICSS was posterio-ventral LH. The extinction curves indicated that it is faster and exponential in case of VTA-SN, but it is slower with longer duration in case of LH-MFB. ICSS of SN were accompanied by exploratory locomotion and head bobbing. Thirty-one percent subjects with SN/VTA stimulation showed rotational behaviour. Seventy-eight percent of subjects with LH stimulations showed stimulus-bound ejaculations. Thirty-two percent of subjects with posterior LH stimulations showed biting of pedal edges. LH stimulations were accompanied by induced seizures and increased grooming in 18% and 13% of subjects, respectively. There was lateralisation of cerebral hemispheric function as right paw preference was noted in majority of rats, whether sites of stimulation were in the left or right cerebral hemisphere. The various other modes of pedal pressing operants like use of paw and mouth, alternate paw dribbling, use of head electrode assembly to manipulate the pedal were also recorded and analysed.

Animals↗

PubMed1996

Dose-response functions of apomorphine, SKF 38393, LY 171555, haloperidol and clonidine on the self-stimulation evoked from lateral hypothalamus and ventral tegmentum.

The experimental animals were implanted with two bipolar electodes, one in the lateral hypothalamus including medial forebrain bundle (LH-MFB) and other in ipsilateral ventral tegmental area-substantia nigra (VTA-SN) and were trained to press a pedal for self-stimulation. This provided the scope to compare directly the effect of a given dose of a drug on the two reward regions in the same animal in the same testing situation. The current intensity was set to produce intracranial self-stimulation (ICSS) response rates of 50% less than the maximal shaping response rates for the respective animals (M60). Following systemic (intraperitoneal) administration of apomorphine (a dopamine receptor D1/D2 mixed agonist), SKF 38393 (D1 > D3 > D2 agonist), LY 17155 or quinpirole (D3 > D2 and D1) agonist), haloperidol (a DA-D2 antagonist), and clonidine (noradrenaline receptor alpha 2 agonist), the ICSS response rates evoked from LH-MFB and VTA-SN were compared with vehicle or saline-treated animals on the basis of dose-response functions. A dose-dependent inhibitory effect at M50 was observed with apomorphine (0.01-1.00 mg/kg) and haloperidol (0.05-0.30 mg/kg) for both the sites of stimulation. These doses of haloperidol did not produce any motor deficits like catalepsy and muscular rigidity. The dose-response and time-effect functions of SKF 38393 and LY 171555 at M50 showed the facilitation and suppression of ICSS of VTA-SN and LH-MFB respectively. Clonidine (0.05-0.25 mg/kg) also produced inhibitory effect on ICSS rates, but this suppression was of different magnitude with respect to the site of stimulation. These doses of clonidine were in the range that did not prevent active pedal pressing responses. ED50 (the dose required to reduce the ICSS response rate 50% of the rate after administration of vehicle) for LY 171555 was 0.8 and 4.4 mg/kg for the ICSS of VTA-SN and LH-MFB respectively and thus statistically different ED50 for apomorphine was 0.27 and 0.36 mg/kg; and for haloperidol was 0.75 and 0.90 mg/kg for LH-MFB and VTA-SN respectively and thus not different significantly. ED50 for clonidine was 0.25 and 0.08 mg/kg for VTA-SN and LH-MFB respectively and thus statistically different. The two-way analysis of variance (ANOVAR) of interaction of dose-response function of alpha 2 agonist with respect to LH-MFB and VTA-SN showed significant independence in their suppressive effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

2, 4-dichloro phenoxy acetic acid alters monoamine levels, acetylcholinesterase activity & operant learning in rats.

2, 4-Dichloro phenoxy acetic acid (2, 4-D) was given at 100 mg/kg body weight per day by oral intubation from postnatal days 2 to 25 to assess its effect on the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), cerebellum (CB) and brainstem (BS). NE levels were increased in OB, HI, VC and BS at 10 days of age. However, by 25 days, NE levels were decreased in OB, HI and VC. DA levels were also increased in OB, HI, VC and CB at 10 days of age and again decreased by 25 days in OB, HI and VC. 5-HT levels were increased in HI, CB and BS at 10 days and in VC and CB at 25 days of age. Reduced acetylcholinesterase (AChE) activity in OB and HI and monoamines in different brain regions at 25 days of age might be responsible for the observed deficits in both acquisition and rate of pedal press response when animals were exposed chronically to 2, 4-D during postnatal brain development.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1996

Subordination induced decrease in 5-hydroxytryptamine and dopamine levels in the frontal cortex--a study using worker-parasite relationship in rats as a model.

Competition for a limited resource appears to be an important factor in natural selection. Such competition when elicited experimentally, leads to the establishment of dominant-subordinate (D-S) relationship between the competitors. The present study was carried out to analyse the effect of D-S relationship on the levels of monoamines, namely, dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in various brain regions. The model of D-S relationship selected for this work was a modified worker-parasite paradigm in adult male Wistar rats. The levels of monoamines were estimated in the frontal cortex, the entorhinal cortex, the hippocampus and the septum of the two competitors and a non-competitor control, using high pressure liquid chromatography (HPLC). Levels of DA and 5-HT, but not NE, were found to be lower (P < 0.05) only in the frontal cortex of the subordinate as compared to that of the dominant or the control. These findings are comparable with similar neurochemical changes reported to be caused by some of the known stressors.

Animals↗

PubMed1995

Effect of chronic restraint stress on dendritic spines and excrescences of hippocampal CA3 pyramidal neurons--a quantitative study.

Effect of chronic restraint stress on the number of dendritic spines and excrescences of hippocampal CA3 pyramidal neurons has been investigated. The results revealed a significant increase in the number of dendritic spines of apical and basal dendrites in rats subjected to restraint stress (6 h per day for 21 days). The number of excrescences were also markedly increased in stressed rats. The physiological significance and possible mechanism for increased spine density is discussed.

Animals↗

PubMed1995

Neurofilament phosphorylation is increased in ventral horn neurons of neonatal rat spinal cord exposed to cerebrospinal fluid from patients with amyotrophic lateral sclerosis.

Aberrant neurofilament (NF) phosphorylation in the soma of the ventral horn neurons of neonatal rat spinal cord is observed following exposure to cerebrospinal fluid (CSF) of patients suffering from Amyotrophic Lateral Sclerosis (ALS). CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3 day old rat pups. After 48 h, sections of spinal cords were stained for the presence of phosphorylated NF epitopes with SMI-31 antibody. The number of neuronal soma staining with this antibody in the ventral and dorsal horns sides of the spinal cord was counted. There was a significant 3-fold increase in the number of soma stained with SMI-31 antibody in the ventral horns of rat spinal cords exposed to CSF of patients with ALS compared to cords from rats exposed to CSF of non-ALS patients and those which were not exposed to any CSF samples. Such an increase in staining of neuronal soma was not observed in the dorsal horns. Hyperphosphorylation of neuronal soma suggests an initial stage of degenerative changes occurring in the motor (ventral horn) neurons following exposure to circulating factor(s) in the CSF of patients with ALS.

Amyotrophic Lateral Sclerosis↗

PubMed1994

Retinal ganglion cell survival and neurite regeneration in vitro after cell death period are dependent upon target derived trophic factor and retinal glial factor(s).

Retinal ganglion cells (RGCs) obtained from the rat retina after the cell death period were maintained in vitro by target derived retinal ganglion cell neurotrophic factor (RGNF). However, only 15% of surviving RGCs expressed neurites. On the other hand, when the culture was supplemented with retinal glia conditioned medium, nearly 80% of surviving RGCs expressed neurites which were longer than two cell diameter. Expression of neurites is not due to the presence of laminin in the glial conditioned medium as laminin coated substratum had no significant effect on the neurite growth from mature RGCs in the absence of glial factors.

Animals↗