Olfactory tract transection reveals robust tissue-level plasticity by cellular numbers and neurotrophic factor expression in olfactory bulb.

Nervous system lesions are characterized by the loss of neuronal numbers and types. The neurotrophic factor levels in an injured tissue reflect their potential for regeneration. This hypothesis was investigated in olfactory bulb (OB), where olfactory tract was surgically transected disrupting neuronal migration and turnover. The effects were followed with quantification of mitral cells and three neurotrophic factors mRNA levels for 6 weeks. The neuronal numbers decreased by 3rd- and 4th-week in transected OBs followed by their restoration, comparable with that of controls at 5th- and 6th-week. The endogenous levels of three neurotrophic factors – (brain derived neurotrophic factor, insulin growth factor-1 and fibroblast growth factor-2) using qPCR showed increase at 2nd-week by 136-, 8- and 2-fold respectively. Also, there was a significant increase in specific neurotrophic factors at 5th-week and 6th-weeks. The results propose a temporal link between deployment of neurotrophic factors and the plausible restorative events for mitral cell numbers in OB.

Olfactory tract transection in neonatal rats: Evidence for Mitral cell regeneration and restoration of functional connectivity with its targets.

Central Nervous System (CNS) regeneration and repair mechanism are two important aspects of functional recovery in the adult central nervous system following brain and spinal cord injury. Following olfactory tract transection in neonatal rats, functional connectivity between the olfactory bulb and the piriform cortex gets re-established by 120 days. The recovery of the dendritic morphology was associated with the synchronized oscillatory activity between olfactory bulb and piriform cortex. Mitral cells which were regenerated after the transection showed profuse branching, indicative of their undifferentiated state. However, normal dendritic morphology could be seen by 120 days after olfactory tract transection. These results thus provide a supportive evidence for the restoration of the functional connections between the olfactory bulb and the piriform cortex at 120 days.

Expression of nestin--a stem cell associated intermediate filament in human CNS tumours.

BACKGROUND & OBJECTIVES: Nestin is an intermediate filament protein expressed in undifferentiated cells during the development of brain and is considered as a marker for neuroepithelial stem cells. Expression of this protein in various CNS tumour cells suggests the possibility of existence of tumour stem cell modulating the evolution. We carried out an immunohistochemical study to demonstrate the expression of nestin and its co-expression with neuronal and glial intermediate filament and correlate with the grade of malignancy. METHODS: Formalin fixed, paraffin processed sections from two human foetuses, 16 brain tumours of both neuronal and glial lineage and two metastatic tumours were immunostained with polyclonal antibody to nestin. Serial sections from primary brain tumours were also stained with monoclonal antibody to neurofilament (NF) and glial fibrillary acidic protein (GFAP). Fluorescent double labeling was carried out on four cases using laser confocal microscopy, to document co-localization of nestin with other intermediate filaments in the tumour cells. RESULTS: Nestin expression was observed along the paraventricular zone of human foetuses and in brain tumours of both glial and neuronal lineage, of both high and low grades of malignancy. In addition, mature dysplastic spinal motor neurons adjacent to tumour and cerebellar Purkinje cells also expressed nestin along with neurofilament. INTERPRETATION & CONCLUSION: Nestin expression was noted in both low and high grade brain tumours and dysplastic neurons and did not parallel the malignant grade of the tumour. The expression of nestin in tumour cells and dysplastic neurons suggests aberrant expression of antigenically primitive proteins in cells to facilitate remodelling of the cell and migration. More studies are needed to elucidate the concept.

Pulmonary functions in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common disabling and progressive neuro-degenerative disorder. Morbidity and mortality are frequently associated with pulmonary dysfunction in patients with PD. AIM: To investigate characteristics of pulmonary function test (PFT) abnormalities in patients with PD and to study the effect of levodopa on the PFT findings. METHODS: Pulmonary function testing was performed in 35 patients with PD during 'off' and 'on' state while on levodopa; and 35 matched healthy controls. RESULTS: The forced vital capacity (FVC) (P < 0.001), maximum voluntary ventilation (MVV) (p < 0.001), maximum expiratory pressure (MEP) (p < 0.001), and maximum inspiratory pressure (MIP) (p < 0.001) were significantly reduced in patients with PD compared to controls. There was significant improvement in the PFT values in 'on' state compared to 'off' state. CONCLUSIONS: A restrictive pattern of pulmonary dysfunction is present in patients with PD, which improves significantly with levodopa. The evaluation and rehabilitation of respiratory disturbances should be routinely included in the management of patients with Parkinson's disease.

Long-term effects of postnatal aluminium exposure on acetylcholinesterase activity and biogenic amine neurotransmitters in rat brain.

The long-term effects of early postnatal exposure to aluminium on acetyl choline esterase (AChE) activity and on biogenic amines were studied in different brain regions. The subjects were eight days old male Wistar rat pups. They were grouped into normal control and aluminium exposed groups. For aluminium exposure, the pups were gastric intubated with aluminium chloride (40 mg/Kg body weight) for two weeks. Control rats were given equal volumes of distilled water. After the treatment, they were rehabilitated for forty days. On the sixtieth day, the rats from both the groups were sacrificed and AChE activity, levels of dopamine, noradrenaline and serotonin were estimated in the cerebral cortex, hippocampus, septum, brainstem and striatum. In the aluminium exposed group: the AChE activity was significantly decreased in the hippocampus, septum, striatum and brainstem; serotonin levels were reduced by 20% in the cortex, hippocampus, septum and striatum; in brain stem, the serotonin level was decreased by 40%. A 60% reduction in noradrenaline levels was observed in the striatum whereas it was reduced by 25% in other regions except in hippocampus. Though dopamine levels were not altered in the cortex, septum and brainstem, they were reduced by 40% in the striatum. The study documents the long-term consequences of exposure to aluminium during the developmental periods.

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.

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.

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.

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.

Plasticity of hippocampal and motor cortical pyramidal neurons induced by self-stimulation experience.

The self-stimulation (SS) induced neuronal plasticity was observed in CA3 hippocampal and layer V motor cortical pyramidal neurons. SS experience was allowed daily for a total of 1 hour for 10 days through four bipolar electrodes implanted bilaterally in lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) in adult male Wistar rats. Examination of pyramidal neurons stained by rapid Golgi technique was made in a total of 1,600 neurons out of 80 rats consisting of 4 groups. The dendritic intersections were quantified upto 200 and 120 microns radial distances in apical and basal dendrites respectively. The CA3 hippocampal and layer V motor cortical pyramidal neurons of SS group revealed significant increase (P < 0.001, two-way ANOVA) in dendritic intersections in both apical and basal dendrites, compared to normal control (NC), sham control (SH) and experimenter-administered (EA) group of animals. These results demonstrate that SS experience promotes increase in dendritic length in hippocampal and motor cortical pyramidal neurons.