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Expression of medium and heavy chain neurofilaments in the developing human auditory cortex

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Abstract

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.

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References

  • Antonini A, Stryker MP (1993) Development of individual geniculocortical arbors in cat striate cortex and effects of binocular impulse blockade. J Neurosci 13:3549–3573

    PubMed  CAS  Google Scholar 

  • 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), Florida

  • 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 USA

  • Boulder Committee (1970) Embryonic vertebrate central nervous system: revised terminology. Anat Rec 166:257–261

    Article  Google Scholar 

  • Bourne JA, Rosa MG (2006) Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT). Cereb Cortex 16(3):405–414

    Article  PubMed  Google Scholar 

  • Bourne JA, Warner CE, Rosa MG (2005) Topographic and laminar maturation of striate cortex in early postnatal marmoset monkeys, as revealed by neurofilament immunohistochemistry. Cereb Cortex 15(6):740–748

    Article  PubMed  Google Scholar 

  • Burkhalter A, Bernardo KL, Charles V (1993) Development of local circuits in human visual cortex. J Neurosci 13:1916–1931

    PubMed  CAS  Google Scholar 

  • Cheour M, Alho K, Ceponiene R, Reinikainen K, Sainio K, Pohjavuori M, Aaltonen ONäätänen R (1998) Maturation of the mismatch negativity in infants. Int J Psychophysiol 29:217–226

    Article  PubMed  CAS  Google Scholar 

  • Cheour-Luhtanen M, Alho K, Kujala T, Sainio K, Reinikainen K, Renlund M, Aaltonen O, Eerola O, Naatanen R (1995) Mismatch negativity indicates vowel discrimination in newborns. Hear Res 82:53–58

    Article  PubMed  CAS  Google Scholar 

  • Cheour-Luhtanen M, Alho K, Sainio K, Rinne T, Reinikainen K, Pohjavuori M, Renlund M, Aaltonen O, Eerola O, Näätänen R (1996) The ontogenetically earliest discriminative response of the human brain. Psychophysiology 33(4):478–481

    Article  PubMed  CAS  Google Scholar 

  • Cheour-Luhtanen M, Alho K, Sainio K, Reinikainen K, Renlund M, Aaltonen O, Eerola O, Näätänen R (1997) The mismatch negativity to speech sounds at the age of three months. Dev Neuropsychol 13:167–174

    Article  Google Scholar 

  • Chiry O, Tardif E, Magistretti PJ, Clarke S (2003) Patterns of calcium-binding proteins support parallel and hierarchical organization of human auditory areas. Eur J Neurosci 17:397–410

    Article  PubMed  Google Scholar 

  • Dehaene-Lambertz G, Dehaene S, Hertz-Pannier L (2002) Functional neuroimaging of speech perception in infants. Science 298:201–205

    Article  Google Scholar 

  • Draganova R, Eswaran H, Murphy P, Huotilainen M, Lowery C, Preissl H (2005) Sound frequency change detection in fetuses and newborns, a magnetoencephalographic study. Neuroimage 28:354–361

    Article  PubMed  Google Scholar 

  • Draganova R, Eswaran H, Murphy P, Lowery C, Preissl H (2007) Serial magnetoencephalographic study of fetal and newborn auditory discriminative evoked responses. Early Hum Dev 83:199–207

    Article  PubMed  Google 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 30:1121–1132

    Article  PubMed  CAS  Google Scholar 

  • Escurat M, Djabali K, Gumpel M, Gros F, Portier MM (1990) Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat. J Neurosci 10:764–784

    PubMed  CAS  Google 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 163:1011–1020

    Article  PubMed  CAS  Google 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 29:1277–1284

    Article  PubMed  CAS  Google Scholar 

  • Groome LJ, Mooney DM, Holland SB, Smith LA, Atterbury JL, Dykman RA (1999) Behavioral state affects heart rate response to low-intensity sound in human fetuses. Early Hum Dev 54:39–54

    Article  PubMed  CAS  Google Scholar 

  • Hashikawa T, Molinari M, Rausell E, Jones EG (1995) Patchy and laminar termination of medial geniculate axons in monkey auditory cortex. J Comp Neurol 362:195–208

    Article  PubMed  CAS  Google Scholar 

  • Haynes RL, Borenstein NS, Desilva TM, Folkerth RD, Liu LG, Volpe JJ, Kinney HC (2005) Axonal development in the cerebral white matter of the human fetus and infant. J Comp Neurol 484:156–167

    Article  PubMed  Google Scholar 

  • Hevner RF (2000) Development of connections in the human visual system during fetal mid-gestation: a DiI-tracing study. J Neuropathol Exp Neurol 59:385–392

    PubMed  CAS  Google Scholar 

  • Hilbig H, Bidmon HJ, Oppermann OT, Remmerbach T (2004) Influence of post-mortem delay and storage temperature on the immunohistochemical detection of antigens in the CNS of mice. Exp Toxicol Pathol 56:159–171

    Article  PubMed  Google Scholar 

  • Hirokawa N, Glicksman MA, Willard MB (1984) Organization of mammalian neurofilament polypeptides within the neuronal cytoskeleton. J Cell Biol 98:1523–1536

    Article  PubMed  CAS  Google Scholar 

  • Hoffman PN, Lasek RJ (1975) The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66:351–366

    Article  PubMed  CAS  Google Scholar 

  • Holst M, Eswaran H, Lowery C, Murphy P, Norton J, Preissl H (2005) Development of auditory evoked fields in human fetuses and newborns: a longitudinal MEG study. Clin Neurophysiol 116:1949–1955

    Article  PubMed  Google Scholar 

  • Iyengar S, Bottjer SW (2002) Development of individual axon arbors in a thalamocortical circuit necessary for song learning in zebra finches. J Neurosci 22:901–911

    PubMed  CAS  Google Scholar 

  • Jacoby RA, Marshak DW (2000) Synaptic connections of DB3 diffuse bipolar cell axons in macaque retina. J Comp Neurol 416:19–29

    Article  PubMed  CAS  Google Scholar 

  • Jardri R, Pins D, Thomas P (2008) A case of fMRI-guided rTMS treatment of coenesthetic hallucinations. Am J Psychiatry 165:1490–1491

    Article  PubMed  Google Scholar 

  • Judas M, Rados M, Jovanov-Milosevic N, Hrabac P, Stern-Padovan R, Kostovic I (2005) Structural, immunocytochemical, and mr imaging properties of periventricular crossroads of growing cortical pathways in preterm infants. AJNR Am J Neuroradiol 26:2671–2684

    PubMed  Google Scholar 

  • Kisilevsky BS, Muir DW, Low JA (1992) Maturation of human fetal responses to vibroacoustic stimulation. Child Dev 63:1497–1508

    Article  PubMed  CAS  Google Scholar 

  • Kisilevsky BS, Hains SM, Lee K, Xie X, Huang H, Ye HH, Zhang K, Wang Z (2003) Effects of experience on fetal voice recognition. Psychol Sci 14:220–224

    Article  PubMed  Google Scholar 

  • Kostovic I, Jovanov-Milosevic N (2006) The development of cerebral connections during the first 20–45 weeks’ gestation. Semin Fetal Neonatal Med 11:415–422

    Article  PubMed  Google Scholar 

  • Kostovic I, Judas M (2010) The development of the subplate and thalamocortical connections in the human foetal brain. Acta Paediatr 99:1119–1127

    Article  PubMed  Google Scholar 

  • Kostovic I, Judas M, Rados M, Hrabac P (2002) Laminar organization of the human fetal cerebrum revealed by histochemical markers and magnetic resonance imaging. Cereb Cortex 12:536–544

    Article  PubMed  Google Scholar 

  • Kriz J, Zhu Q, Julien JP, Padjen AL (2000) Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H. Brain Res 885:32–44

    Article  PubMed  CAS  Google Scholar 

  • Krmpotic-Nemanic J, Kostovic I, Kelovic Z, Nemanic D (1980) Development of acetylcholinesterase (AChE) staining in human fetal auditory cortex. Acta Otolaryngol 89:388–392

    Article  PubMed  CAS  Google Scholar 

  • Krmpotic-Nemanic J, Kostovic I, Kelovic Z, Nemanic D, Mrzljak L (1983) Development of the human fetal auditory cortex: growth of afferent fibres. Acta Anat (Basel) 116:69–73

    Article  CAS  Google Scholar 

  • Kuhl PK (2004) Early language acquisition: cracking the speech code. Nat Rev Neurosci 5:831–843

    Article  PubMed  CAS  Google Scholar 

  • Kushnerenko E, Ceponiene R, Balan P, Fellman V, Huotilainen M, Naatanen R (2002) Maturation of the auditory event-related potentials during the 1st year of life. Neuroreport 13:47–51

    Article  PubMed  Google Scholar 

  • Lee MK, Cleveland DW (1996) Neuronal intermediate filaments. Annu Rev Neurosci 19:187–217

    Article  PubMed  CAS  Google Scholar 

  • Marin-Padilla M (1990) Three-dimensional structural organization of layer I of the human cerebral cortex: a Golgi study. J Comp Neurol 299:89–105

    Article  PubMed  CAS  Google Scholar 

  • Marin-Padilla M (1992) Ontogenesis of the pyramidal cell of the mammalian neocortex and developmental cytoarchitectonics: a unifying theory. J Comp Neurol 321:223–240

    Article  PubMed  CAS  Google Scholar 

  • Martin R, Door R, Ziegler A, Warchol W, Hahn J, Breitig D (1999) Neurofilament phosphorylation and axon diameter in the squid giant fibre system. Neuroscience 88:327–336

    Article  PubMed  CAS  Google Scholar 

  • Mehler J, Jusczyk P, Lambertz G, Halsted N, Bertoncini J, Amiel-Tison C (1988) A precursor of language acquisition in young infants. Cognition 29:143–178

    Article  PubMed  CAS  Google Scholar 

  • Moore JK (2002) Maturation of human auditory cortex: implications for speech perception. Ann Otol Rhinol Laryngol Suppl 189:7–10

    PubMed  Google Scholar 

  • Moore JK, Guan YL (2001) Cytoarchitectural and axonal maturation in human auditory cortex. J Assoc Res Otolaryngol 2:297–311

    Article  PubMed  CAS  Google Scholar 

  • Moore JK, Linthicum FH Jr (2007) The human auditory system: a timeline of development. Int J Audiol 46(9):460–478

    Article  PubMed  Google Scholar 

  • Moore JK, Perazzo LM, Braun A (1995) Time course of axonal myelination in the human brainstem auditory pathway. Hear Res 87:21–31

    Article  PubMed  CAS  Google Scholar 

  • Moore JK, Guan YL, Shi SR (1997) Axogenesis in the human fetal auditory system, demonstrated by neurofilament immunohistochemistry. Anat Embryol (Berl) 195:15–30

    Article  CAS  Google Scholar 

  • Morlet T, Lapillonne A, Ferber C, Duclaux R, Sann L, Putet G, Salle B, Collet L (1995) Spontaneous Otoacoustic emissions in preterm neonates: prevalence and gender effects. Hear Res 90(1–2):44–54

    Article  PubMed  CAS  Google Scholar 

  • Ohara O, Gahara Y, Miyake T, Teraoka H, Kitamura T (1993) Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J Cell Biol 121:387–395

    Article  PubMed  CAS  Google Scholar 

  • Pasman JW, Rotteveel JJ, de Graaf R, Maassen B, Notermans SLH (1991) Detectability of auditory evoked response components in preterm infants. Early Hum Dev 26:129–141

    Article  PubMed  CAS  Google Scholar 

  • Pasman JW, Rotteveel JJ, de Graaf R, Stegeman DF, Visco YM (1992) The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs). Early Hum Dev 31:113–129

    Article  PubMed  CAS  Google 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

  • Plioplys AV, Gravel C, Hawkes R (1986) Selective suppression of neurofilament antigen expression in the hypothyroid rat cerebral cortex. J Neurol Sci 75:53–68

    Article  PubMed  CAS  Google Scholar 

  • Ponton CW, Moore JK, Eggermont JJ (1996) Auditory brain stem response generation by parallel pathways: differential maturation of axonal conduction time and synaptic transmission. Ear Hear 17:402–410

    Article  PubMed  CAS  Google Scholar 

  • Pujol J, Soriano-Mas C, Ortiz H, Sebastia′n-Galle′s N, Losilla JM, Deus J (2006) Myelination of language-related areas in the developing brain. Neurology 66:339–343

    Article  PubMed  CAS  Google Scholar 

  • Querleu D, Renard X, Boutteville C, Crepin G (1989) Hearing by the human fetus? Semin Perinatol 13:409–420

    PubMed  CAS  Google Scholar 

  • Radnikow G, Feldmeyer D, Lubke J (2002) Axonal projection, input and output synapses, and synaptic physiology of Cajal-Retzius cells in the developing rat neocortex. J Neurosci 22:6908–6919

    PubMed  CAS  Google Scholar 

  • Ramus F, Hauser MD, Miller C, Morris D, Mehler J (2000) Language discrimination by human newborns and by cotton-top tamarin monkeys. Science 288:349–351

    Article  PubMed  CAS  Google Scholar 

  • 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):681–693

    Article  PubMed  CAS  Google Scholar 

  • Rivier F, Clarke S (1997) Cytochrome oxidase, acetylcholinesterase, and NADPH-diaphorase staining in human supratemporal and insular cortex: evidence for multiple auditory areas. Neuroimage 6:288–304

    Article  PubMed  CAS  Google Scholar 

  • Sailaja K, Ahuja RK, Gopinath G (1996) Biparietal diameter: a useful measure for determining gestational age of human abortuses. Natl Med J India 9:165–167

    PubMed  CAS  Google Scholar 

  • Sakaguchi T, Okada M, Kitamura T, Kawasaki K (1993) Reduced diameter and conduction velocity of myelinated fibers in the sciatic nerve of a neurofilament-deficient mutant quail. Neurosci Lett 153:65–68

    Article  PubMed  CAS  Google Scholar 

  • Sarnat HB, Flores-Sarnat L (2002a) Cajal-Retzius and subplate neurons: their role in cortical development. Eur J Paediatr Neurol 6:91–97

    Article  PubMed  Google Scholar 

  • Sarnat HB, Flores-Sarnat L (2002b) Role of Cajal-Retzius and subplate neurons in cerebral cortical development. Semin Pediatr Neurol 9:302–308

    Article  PubMed  Google Scholar 

  • Sarnat HB, Flores-Sarnat L, Trevenen CL (2010) Synaptophysin immunoreactivity in the human hippocampus and neocortex from 6 to 41 weeks of gestation. J Neuropathol Exp Neurol 69:234–245

    Article  PubMed  Google Scholar 

  • Schlaepfer WW, Bruce J (1991) Simultaneous up-regulation of neurofilament proteins during the postnatal development of the rat nervous system. J Neurosci Res 25:39–49

    Article  Google Scholar 

  • Seki T, Arai Y (1999) Different polysialic acid-neural cell adhesion molecule expression patterns in distinct types of mossy fiber boutons in the adult hippocampus. J Comp Neurol 410:115–125

    Article  PubMed  CAS  Google Scholar 

  • Sheridan CJ, Matuz T, Draganova R, Eswaran H, Preissl H (2010) Fetal magnetoencephalography—achievements and challenges in the study of prenatal and early postnatal brain responses: a review. Infant Child Dev 19:80–93

    Article  PubMed  Google Scholar 

  • Tapscott SJ, Bennett GS, Holtzer H (1981) Neuronal precursor cells in the chick neural tube express neurofilament proteins. Nature 292:836–838

    Article  PubMed  CAS  Google Scholar 

  • Tardif E, Clarke S (2001) Intrinsic connectivity of human auditory areas: a tracing study with DiI. Eur J Neurosci 13:1045–1050

    Article  PubMed  CAS  Google Scholar 

  • Ulfig N, Chan WY (2002) Axonal patterns in the prosencephalon of the human developing brain. Neuroembryology 1:4–16

    Article  CAS  Google Scholar 

  • Ulfig N, Nickel J, Bohl J (1998) Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain. Cell Tissue Res 291:433–443

    Article  PubMed  CAS  Google Scholar 

  • Verney C, Derer P (1995) Cajal-Retzius neurons in human cerebral cortex at midgestation show immunoreactivity for neurofilament and calcium-binding proteins. J Comp Neurol 359:144–153

    Article  PubMed  CAS  Google Scholar 

  • von Economo C, Koskinas GN (1925) Die Cytoarchitectonik der Hirnrinde des erwachsenen Menschen. Julius Springer, Berlin

    Google Scholar 

  • Vouloumanos A, Werker JF (2007) Listening to language at birth: evidence for a bias for speech in neonates. Dev Sci. 10:159–164

    Article  PubMed  Google Scholar 

  • Zecevic N, Milosevic A, Rakic S, Marin-Padilla M (1999) Early development and composition of the human primordial plexiform layer: an immunohistochemical study. J Comp Neurol 412:241–254

    Article  PubMed  CAS  Google Scholar 

  • Zhu Q, Couillard-Despres S, Julien JP (1997) Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol 148:299–316

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

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.

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Authors and Affiliations

  1. Division of Systems Neuroscience, National Brain Research Centre (Deemed University), NH-8, Manesar, Gurgaon, 122050, Haryana, India

    Arvind Singh Pundir, L. Shahul Hameed & Soumya Iyengar

  2. Department of Forensic Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi, 110002, India

    P. C. Dikshit

  3. Department of Obstetrics and Gynecology, Base Hospital, Delhi Cantonment, Delhi, 110010, India

    Praveen Kumar & Surender Mohan

  4. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India

    Bishan Radotra

  5. Department of Neuropathology, National Institute of Mental Health and Allied Sciences, Hosur Road, Bangalore, 560029, India

    S. K. Shankar & Anita Mahadevan

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  1. Arvind Singh Pundir
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Correspondence to Soumya Iyengar.

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A. S. Pundir and L. S. Hameed contributed equally to this paper.

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429_2011_352_MOESM1_ESM.tif

Supplementary Figure 1 Negative controls for immunohistochemistry using SMI-312 and SMI-31 demonstrate the absence of staining in coronal sections of the Heschl’s gyrus at 15GW, 25GW, 32GW, 40GW, 9 postnatal months and an adult (36 yr). Scale bar = 20 μm. (TIFF 5,475 kb)

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Pundir, A.S., Hameed, L.S., Dikshit, P.C. et al. Expression of medium and heavy chain neurofilaments in the developing human auditory cortex. Brain Struct Funct 217, 303–321 (2012). https://doi.org/10.1007/s00429-011-0352-7

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