Biomedical subjects

M K Lakshmana

Publications and source records attributed to M K Lakshmana.

14 recordsLinked to original sources

PubMed1998

Chronic (-) deprenyl administration increases dendritic arborization in CA3 neurons of hippocampus and AChE activity in specific regions of the primate brain.

The mechanism by which (-) deprenyl enhances cognitive function in Alzheimer's disease (AD) is not yet understood. (-) Deprenyl (0.2 mg/kg/day) was administered intramuscularly to adult male monkeys (n = 6) for 25 days. Control monkeys (n = 6) received physiological saline by the same route. The activity of acetylcholinesterase (AChE) in different brain regions and the dendritic arborization in CA3 pyramidal neurons of hippocampus were analysed. (-) Deprenyl-treated monkeys showed a significant increase in the AChE activity by 43% (p < 0.001) in the frontal cortex, by 39% (p < 0.025) in the motor cortex, by 66% (p < 0.001) in the hippocampus and by 26% (p < 0.05) in the striatum compared to controls. The branching points and the intersections of both apical and basal dendrites of CA3 hippocampal pyramidal neurons were also significantly increased in (-) deprenyl-treated monkeys. Enhanced AChE activity may increase dendritic arborization in the hippocampus and it may also play a role in improving cognitive functions observed in AD, following (-) deprenyl treatment.

Acetylcholinesterase↗

PubMed1998

(-)-Deprenyl attenuates spinal motor neuron degeneration and associated locomotor deficits in rats subjected to spinal cord ischemia.

We have evaluated potential neuroprotection offered by (-)-deprenyl on degenerating motor neurons of the spinal cord when subjected to transient ischemia. Thirty-six healthy adult male Wistar rats were trained for a motor function test in a staircase maze and randomly but equally (n = 6) grouped into normal control, sham control, ischemia (IS), IS rats treated with vehicle (IV), and rats treated with low (0.1 mg/kg) and high (1.0 mg/kg) doses of (-)-deprenyl. (-)-Deprenyl was given intraperitoneally 30 min after the induction of ischemia and thereafter everyday for 14 days. Spinal cord ischemia was produced at the lumbar level in conscious rats by occluding the abdominal aorta just below the branching point of the left renal artery for 30 min. Analysis of the motor performance in all groups of rats revealed a significant (P < 0.001) increase in the time taken to cross the run way of the maze, in i.s. and i.v. rats compared to all other groups of rats. In addition, qualitative and quantitative examination of spinal motor neurons at the lumbar level showed a significant (P < 0.001) decrease in the number of healthy motor neurons in i.s. and i.v. rats compared to controls. Postischemic administration of (-)-deprenyl, at both doses, significantly prevented motor neuron degeneration and the associated locomotor deficits in IS rats.

Animals↗

PubMed1998

Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain.

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.

3,4-Dihydroxyphenylacetic Acid↗

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

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↗

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

Increased acetylcholinesterase activity in selected regions of rat brain after chronic (-)-deprenyl administration.

(-)-Deprenyl, 0.05, 1.0, 2.0, and 10.0 mg/kg body weight, was administered intraperitonially to Wistar rats for 30 days. The activity of acetylcholinesterase, and monoamine oxidase A and B were assayed in different brain regions. After the experimental period acetyl cholinesterase activity was found to be significantly increased in frontal cortex [P < 0.001] and hippocampus [P < 0.001] but not in striatum and brainstem at 0.1, 1.0, and 2.0 mg/kg dose, the maximum increase being at 0.1 mg/kg dose. Monoamine oxidase B activity was inhibited by more than 90% at 1.0, 2.0, and 10.0 mg/kg dose while 0.05 and 0.1 dose inhibited only about 55% and 70% respectively. Monoamine oxidase A activity was inhibited to more than 70% at 1.0 mg dose and to more than 90% at 2.0 and 10.0 mg/kg dose. At 0.05 and 0.1 mg/kg dose monoamine oxidase A activity was not significantly altered.

Acetylcholinesterase↗

PubMed1996

Phenobarbital in the anticonvulsant dose range does not impair learning and memory or alter brain AChE activity or monoamine levels.

The learning and memory in adult, male Wistar rats were assessed using the T-maze and passive avoidance tests after chronic administration of phenobarbital (PB) at 5, 15, 30, 60, or 75 mg/kg intraperitoneally (IP) for 21 days. The PB levels in plasma, the acetylcholine esterase (AChE) activity in the motor cortex, pyriform cortex, olfactory bulb, striatum, septum, and hippocampus and the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels in the hippocampus were measured. There was no significant change in learning and memory, AChE activity, or monoamine levels at plasma PB levels of 1.5, 6.0, 9.0, and 25 micrograms/ml (corresponding to doses of 5, 15, 30, or 60 mg/kg PB, respectively). However, at a plasma level of 55 micrograms/ml (75 mg/kg), PB caused impairment in learning and memory. It was associated with an increase in AChE activity and 5-HT levels in the hippocampus. The results indicate that chronic PB administration may not be linked to impaired learning and memory functions at doses used in anticonvulsant therapy.

Acetylcholinesterase↗

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

Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels.

Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5, 25, 50, or 75 mg/kg i.p. for 21 days. The learning and memory of these rats were assessed using the T-maze and passive avoidance tests. The plasma DPH levels, acetylcholine esterase (AChE) activity in different brain regions, and the levels of monoamines in the hippocampus were measured. The results indicate that DPH below the therapeutic plasma level did not significantly impair learning and memory. Correspondingly, no changes were noted in the brain 5-HT or AChE activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5 micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats. The impaired learning and memory functions were associated with increased 5-HT levels and decreased AChE activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction in the AChE activity in the striatum, in addition to hippocampus. It is conjectured that the neurochemical changes brought about by DPH at therapeutic plasma levels may account for the impairment of learning, memory, and cognitive functions in epilepsy.

Acetylcholinesterase↗

PubMed1995

Changes in learning and memory, acetylcholinesterase activity and monoamines in brain after chronic carbamazepine administration in rats.

Groups of adult male Wistar rats were administered carbamazepine (CBZ) in doses of 5, 10, 20, 40 or 80 mg/kg/day intraperitoneally (i.p.) for 21 days. The learning and memory of the rats were assessed by the T-maze and passive avoidance tests. The CBZ plasma levels, the activity of acetylcholinesterase (AChE) in different brain regions, and the levels of monoamines in the hippocampus were also measured. None of the administered doses of CBZ impaired learning and memory. Rats with CBZ plasma levels of 2.5 and 4.5 micrograms/ml corresponding to the doses of 20 and 40 mg/kg, learned significantly better than controls. AChE activity was decreased in hippocampus and pyriform cortex (19%) in these groups. Simultaneously, an increase in the serotonin (5-HT) (36%) and dopamine (137%) levels in the hippocampus was noted in the 20-mg/kg CBZ group. 5-Hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) levels were increased at 10-, 20-, and 40-mg/kg CBZ doses. However, a dose of 80-mg/kg caused no change in learning performance as compared with that of controls. Correspondingly, no changes were evident in the AChE activity or monoamine levels. We postulated that the decreased AChE activity caused by CBZ in the therapeutic range may lead to increased ACh levels in brain, thus producing improvement in learning and memory. The increased turnover of 5-HT and dopamine (DA) in the hippocampus may play a role in long-term potentiation and improvement in memory.

Acetylcholinesterase↗

PubMed1994

Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance.

The organochlorine insecticide, endosulfan was administered (6 mg/kg body weight) to Wistar rat pups of both sexes by gastric intubation daily from post-natal days 2-25. Its effect on levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) was assayed in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), brainstem (BS) and cerebellum (CB) on days 10 and 25 using high-performance liquid chromatography (HPLC). The activity of acetylcholinesterase (AChE) was also estimated in the same regions of the brain. Performance in operant conditioning for solid food reward was assessed in 25-day-old rats. NA levels were increased in OB (12%, P < 0.01) and BS (10%, P < 0.05) at 10 days of age and in HI (20%, P < 0.01) and CB (12%, P < 0.05) at 25 days of age. DA level was decreased in HI at both 10 (42%, P < 0.001) and 25 (45%, P < 0.001) days. Serotonin levels were increased in OB (12%, P < 0.05), HI (41%, P < 0.001), VC (30%, P < 0.01) and BS (15%, P < 0.01) at 10 days of age but at 25 days, levels were decreased in BS (20%, P < 0.05) and CB (31%, P < 0.01). The activity of AChE was not different from the control groups in any of the regions studied. These data suggest that monoaminergic systems in the developing rat brain respond to endosulfan by undergoing something like a 'reorganization'. However, such changes do not ameliorate certain functional losses following the exposure to endosulfan as operant conditioning revealed deficits in acquisition as well as retention of memory.

Acetylcholinesterase↗

PubMed1993

Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development.

Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatum-accumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning revealed a deficiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage.

Acetylcholinesterase↗