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Age Related and Hypothyroidism Related Changes on the Stoichiometry of Neurofilament Subunits in the Developing Rat Brain

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Title Age Related and Hypothyroidism Related Changes on the Stoichiometry of Neurofilament Subunits in the Developing Rat Brain
 
Creator Chinnakkaruppan, A
Das, Sumantra
Sarkar, Pranab K
 
Subject Cell Biology & Physiology
 
Description Hypothyroidism in the developing brain results in progressive intraneuronal accumulation of
neurofilament (NF) proteins in the proximal hillock regions of axons, analogous to the pathological
intraneuronal accumulation of NF in common neurodegenerative diseases like Alzheimer’s disease,
Parkinson’s disease and Amyotrophic lateral sclerosis. A preferential decline in the expression of the light
chain of NF occurs in all the three diseases leading to an absolute change in stoichiometry of the NF
subunits. Using the developing hypothyroid rat cerebra as a model, we have tried to elucidate if age or
hypothyroidism causes a change in the stoichiometry or molar ratio of the NF subunits which could be
responsible for their aberrant intraneuronal accumulation.
Western blotting and chemiluminescence assay of cytoskeletal preparations from normal and
hypothyroid developing rats at postnatal days 5 (PND5), PND15 and PND25 shows that in the normal
cerebra, the expression of NFL and NFM were abundant during the first 2 weeks, corresponding to the
onset of axonal outgrowth and synaptogenesis, whereas that of NFH was predominant during the second
and third weeks corresponding to the period of maturation of synapses, axonal caliber and transport
processes. These results show that consistent with the requirement for neuronal differentiation during
synaptogenesis, the molar ratios NFH:NFM:NFL changed significantly from 1:3:9 at PND5 to 1:2:6 at
PND25. Hypothyroidism caused a 40–60% decline in the expression of all three subunits. However, at all
three ages examined, differences in themolar ratios of the NF subunits between normal and hypothyroid
cerebra were insignificant suggesting that factors other than alteration in the stoichiometry of NF
subunits are associated with their aberrant intraneuronal aggregation.
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1060/1/2009%2DIJDN.pdf
Chinnakkaruppan, A and Das, Sumantra and Sarkar, Pranab K (2009) Age Related and Hypothyroidism Related Changes on the Stoichiometry of Neurofilament Subunits in the Developing Rat Brain. International Journal of Developmental Neuroscience, 27. pp. 257-261.
 
Relation http://dx.doi.org/10.1016/j.ijdevneu.2008.12.007
http://www.eprints.iicb.res.in/1060/