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