Nandhu, M S; Dr. Paulose, C S(Cochin University of Science and Technology, March , 2011)
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Abstract:
Parkinson's disease is a chronic progressive neurodegenerative movement
disorder characterized by a profound and selective loss of nigrostriatal dopaminergic
neurons. Our findings demonstrated that glutamatergic system is impaired during PD.
The evaluations of these damages have important implications in understanding the
molecular mechanism underlying motor, cognitive and memory deficits in PD. Our
results showed a significant increase of glutamate content in the brain regions of 6-
OHDA infused rat compared to control. This increased glutamate content caused an
increase in glutamatergic and NMDA receptors function. Glutamate receptor
subtypes- NMDAR1, NMDA2B and mGluR5 have differential regulatory role in
different brain regions during PD. The second messenger studies confirmed that the
changes in the receptor levels alter the IP3, cAMP and cGMP content. The alteration
in the second messengers level increased the expression of pro-apoptotic factors - Bax
and TNF-α, intercellular protein - α-synuclein and reduced the expression of
transcription factor - CREB. These neurofunctional variations are the key contributors
to motor and cognitive abnormalities associated with PD. Nestin and GFAP
expression study confirmed that 5-HT and GABA induced the differentiation and
proliferation of the BMC to neurons and glial cells in the SNpc of rats. We also
observed that activated astrocytes are playing a crucial role in the proliferation of
transplanted BMC which makes them significant for stem cell-based therapy. Our
molecular and behavioural results showed that 5-HT and GABA along with BMC
potentiates a restorative effect by reversing the alterations in glutamate receptor
binding, gene expression and behaviour abnormality that occur during PD. The
therapeutic significance in Parkinson’s disease is of prominence.
Description:
Department of Biotechnology, Cochin University of
Science and Technology
Jes,Paul; Dr. Paulose, C S(Cochin University of Science and Technology, February , 2011)
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Abstract:
In the present study, the effects of 5-HT, GABA and Bone Marrow Cells
infused intranigrally to substantia nigra individually and in combinations on
unilateral rotenone infused Parkinsonism induced rats. Scatchard analysis of DA,
DA D1 and D2 receptors in the corpus striatum, cerebral cortex, cerebellum, brain
stem and hippocampus showed a significant increase in the Brain regions of
rotenone infused rat compared to control. Real Time PCR amplification of DA D1,
D2, Bax and ubiquitin carboxy-terminal hydrolase were up regulated in the brain
regions of rotenone infused rats compared to control. Gene expression studies of
-Synuclien, cGMP and Cyclic AMP response element-binding protein showed a
significant down regulation in Rotenone infused rats compared to control.
Behavioural studies were carried out to confirm the biochemical and molecular
studies.Our study demonstrated that BMC administration alone cannot reverse the
above said molecular changes occurring in PD rat. 5-HT and GABA acting
through their specific receptors in combination with bone marrow cells play a
crucial role in the functional recovery of PD rats. 5-HT, GABA and Bone marrow
cells treated PD rats showed significant reversal to control in DA receptor binding
and gene expression. 5-HT and GABA have co-mitogenic property. Proliferation
and differentiation of cells re-establishing the connections in Parkinson's disease facilitates the functional recovery. Thus, it is evident that 5-HT and GABA along
with BMC to rotenone infused rats renders protection against oxidative, related
motor and cognitive deficits which makes them clinically significant for cellbased
therapy. The BMC transformed to neurons when co-transplanted
with 5-HT and GABA which was confirmed with PKH2GL and nestin.
These newly formed neurons have functional significance in the therapeutic
recovery of Parkinson’s disease.
Description:
Department
of Biotechnology, Cochin University of Science and Technology
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