Anju, T R; Dr. Paulose, C S(Cochin University of Science and Technology, September , 2010)
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Abstract:
The present study was designed to investigate the protective effect of
glucose, oxygen and epinephrine resuscitation on impairment in the functional role
of GABAergic, serotonergic, muscarinic receptors, PLC, BAX, SOD, CAT and
GPx expression in the brain regions of hypoxia induced neonatal rats. Also, the
role of hormones - Triiodothyronine (T3) and insulin, second messengers –
cAMP, cGMP and IP3 and transcription factors – HIF and CREB in the regulation
of neonatal hypoxia and its resuscitation methods were studied. Behavioural
studies were conducted to evaluate the motor function and cognitive deficit in one
month old control and experimental rats. The efficient and timely supplementation
of glucose plays a crucial role in correcting the molecular changes due to hypoxia,
oxygen and epinephrine. The sequence of glucose, epinephrine and oxygen
administration at the molecular level is an important aspect of the study. The
additive neuronal damage effect due to oxygen and epinephrine treatment is
another important observation. The corrective measures by initial supply of
glucose to hypoxic neonatal rats showed from the molecular study when brought
to practice will lead to healthy intellectual capacity during the later developmental
stages, which has immense clinical significance in neonatal care.
Description:
Department of Biotechnology,
Cochin University of Science and Technology
Korah, Kuruvilla P; Dr. Paulose, C S(Cochin University of Science and Technology, May 23, 2012)
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Abstract:
Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the SNpc resulting in severe motor impairments. Serotonergic system plays an important regulatory role in the pathophysiology of PD in rats, the evaluation of which provides valuable insight on the underlying mechanisms of motor, cognitive and memory deficits in PD. We observed a decrease in 5-HT content in the brain regions of 6-OHDA infused rat compared to control. The decreased 5-HT content resulted in a decrease of total 5-HT, 5-HT2A receptors and 5-HTT function and an increase of 5-HT2C receptor function. 5-HT receptor subtypes - 5-HT2A and 5-HT2C receptors have differential regulatory role on the modulation of DA neurotransmission in different brain regions during PD. Our observation of impaired serotonergic neurotransmission in SNpc, corpus striatum, cerebral cortex, hippocampus, cerebellum and brain stem demonstrate that although PD primarily results from neurodegeneration in the SNpc, the associated neurochemical changes in other areas of the brain significantly contributes to the different motor and non motor symptoms of PD. The antioxidant enzymes – SOD, CAT and GPx showed significant down regulation which indicates increased oxidative damage resulting in neurodegeneration. We also observed an increase in the level of lipid peroxidation. Reduced expression of anti-apoptotic Akt and enhanced expression of NF-B resulting from oxidative stress caused an activation of caspase-8 thus leading the cells to neurodegeneration by apoptosis. BMC administration in combination with 5-HT and GABA to PD rats showed reversal of the impaired serotonergic neurotransmission and oxidative stress mediated apoptosis. The transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the SNpc along with an increase in DA content and an enhanced expression of TH. Neurotrophic factors – BDNF and GDNF rendered neuroprotective effects accompanied by improvement in behavioural deficits indicating a significant reversal of altered dopaminergic and serotonergic neurotransmission in PD. The restorative and neuroprotective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of PD.
Description:
Department of Biotechnology, Cochin University
of Science and Technology,