Expression of medium and heavy chain neurofilaments in the developing human auditory cortex
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Neurofilament medium (NF-M) and heavy (NF-H) chain proteins have been used as markers for maturity in the developing brain since their accumulation in axons leads to an increase in conduction velocity. Earlier studies have demonstrated immunoreactivity of neurofilaments in Layer I of the human auditory cortex at 22 gestation weeks (GW), whereas that in other layers developed between 1 and 12 postnatal years, suggesting a gradual increase in the processing of sounds. However, third trimester fetuses and infants are fairly sophisticated in their ability to discern different aspects of complex sounds. Given these contradictory findings, we decided to study the expression of neurofilaments in human auditory cortex between 15 GW and adulthood. We found that mRNA and protein for both NF-M and NF-H were present in the presumptive human auditory cortex in the second trimester and during the postnatal period (1 year—adulthood). Axons in all layers of the auditory cortex were immunoreactive for neurofilaments by 25 GW and the density of the neurofilament-rich plexus in the cortical wall became adult-like during the first postnatal year in humans (9 postnatal months). Our results suggest that in terms of neurofilament expression, axons within the preterm human auditory cortex may be more mature than previously thought.
KeywordsAuditory cortex Fetal human brain Heavy chain neurofilament protein Heschl’s gyrus Immunohistochemistry for SMI-312 and SMI-31 Medium chain neurofilament protein
This work was supported by intramural funds from the National Brain Research Centre, Manesar. The authors gratefully acknowledge the support provided by Prof. V Ravindranath (IISc, Bangalore, former Director, NBRC), Dr. TS Rao (Director, DBT), and Dr. OP Sharma for setting up the collection of postmortem tissue at NBRC, Ram Mehar (NBRC, Manesar) for technical support and Nikhil Ahuja and Neha Sehgal (NBRC, Manesar) for help with the methods.
- Bayer SA, Altman J (2005a) The Human Brain during the Second Trimester, Atlas of Human Central Nervous System Development, vol. 3, CRC Press (Taylor and Francis group), FloridaGoogle Scholar
- Bayer SA, Altman J (2005b) The Human Brain during the Third Trimester, Atlas of Human Central Nervous System Development, vol. 2, CRC Press (Taylor and Francis group), Florida USAGoogle Scholar
- Dubois J, Hertz-Pannier L, Dehaene-Lambertz G, Cointepas Y, Le Bihan D (2006) Assessment of the early organization and maturation of infants’ cerebral white matter fiber bundles: a feasibility study using quantitative diffusion tensor imaging and tractography. NeuroImage 30:1121–1132PubMedCrossRefGoogle Scholar
- Garcia ML, Lobsiger CS, Shah SB, Deerinck TJ, Crum J, Young D, Ward CM, Crawford TO, Gotow T, Uchiyama Y, Ellisman MH, Calcutt NA, Cleveland DW (2003) NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth. J Cell Biol 163:1011–1020PubMedCrossRefGoogle Scholar
- Garcia ML, Rao MV, Fujimoto J, Garcia VB, Shah SB, Crum J, Gotow T, Uchiyama Y, Ellisman M, Calcutt NA, Cleveland DW (2009) Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth. J Neurosci 29:1277–1284PubMedCrossRefGoogle Scholar
- Paulussen M, Jacobs S, Van der Gucht E, Hof PR, Arckens L (2011) Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit. Brain Struct Funct. doi: 10.1007/s00429-011-0311-3
- Rao MV, Garcia ML, Miyazaki Y, Gotow T, Yuan A, Mattina S, Ward CM, Calcutt NA, Uchiyama Y, Nixon RA, Cleveland DW (2002) Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport. J Cell Biol 158(4):681–693PubMedCrossRefGoogle Scholar
- von Economo C, Koskinas GN (1925) Die Cytoarchitectonik der Hirnrinde des erwachsenen Menschen. Julius Springer, BerlinGoogle Scholar