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Vol. 32, No. 3, 2010
Issue release date: August 2010
Free Access
Dev Neurosci 2010;32:238–248
(DOI:10.1159/000314341)

Gestational and Neonatal Iron Deficiency Alters Apical Dendrite Structure of CA1 Pyramidal Neurons in Adult Rat Hippocampus

Brunette K.E.a, b · Tran P.V.b, c · Wobken J.D.b · Carlson E.S.a, b, d · Georgieff M.K.a–c
aGraduate Program in Neuroscience, bDepartment of Pediatrics, cCenter for Neurobehavioral Development, dMedical Scientist Training Program, University of Minnesota, Minneapolis, Minn., USA
email Corresponding Author

Abstract

The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.


 goto top of outline Key Words

  • Development
  • Dendritogenesis
  • Spinehead
  • Anemia
  • Cognition
  • Nutrient
  • Cofilin
  • Profilin

 goto top of outline Abstract

The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Degano AL, Pasterkamp RJ, Ronnett GV: MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering semaphorin 3F function. Mol Cell Neurosci 2009;42:243–254.
  2. Bagot RC, van Hasselt FN, Champagne DL, Meaney MJ, Krugers HJ, Joels M: Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiol Learn Mem 2009;92:292–300.
  3. Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joels M, Krugers H: Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 2008;28:6037–6045.
  4. Williams CL: Food for thought: brain, genes, and nutrition. Brain Res 2008;1237:1–4.
  5. Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, Deregnier RA: Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 2004;55:1034–1041.
  6. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW: Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:E51.
  7. Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver SP, Ramey SL, Nelson KG: Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 2002;140:165–170.
  8. Riggins T, Miller NC, Bauer PJ, Georgieff MK, Nelson CA: Electrophysiological indices of memory for temporal order in early childhood: implications for the development of recollection. Dev Sci 2009;12:209–219.
  9. Lozoff B, Jimenez E, Smith JB: Double burden of iron deficiency in infancy and low socioeconomic status: a longitudinal analysis of cognitive test scores to age 19 years. Arch Pediatr Adolesc Med 2006;160:1108–1113.
  10. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T: Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006;64:S34–43; discussion S72–S91.
  11. McEchron MD, Cheng AY, Liu H, Connor JR, Gilmartin MR: Perinatal nutritional iron deficiency permanently impairs hippocampus-dependent trace fear conditioning in rats. Nutr Neurosci 2005;8:195–206.
  12. Gewirtz JC, Hamilton KL, Babu MA, Wobken JD, Georgieff MK: Effects of gestational iron deficiency on fear conditioning in juvenile and adult rats. Brain Res 2008;1237:195–203.
  13. Jorgenson LA, Wobken JD, Georgieff MK: Perinatal iron deficiency alters apical dendritic growth in hippocampal CA1 pyramidal neurons. Dev Neurosci 2003;25:412–420.
  14. Jorgenson LA, Sun M, O’Connor M, Georgieff MK: Fetal iron deficiency disrupts the maturation of synaptic function and efficacy in area CA1 of the developing rat hippocampus. Hippocampus 2005;15:1094–1102.
  15. Rao R, Tkac I, Townsend EL, Gruetter R, Georgieff MK: Perinatal iron deficiency alters the neurochemical profile of the developing rat hippocampus. J Nutr 2003;133:3215–3221.
  16. Carlson ES, Stead JD, Neal CR, Petryk A, Georgieff MK: Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus. Hippocampus 2007;17:679–691.
  17. Ackermann M, Matus A: Activity-induced targeting of profilin and stabilization of dendritic spine morphology. Nat Neurosci 2003;6:1194–1200.
  18. Ethell IM, Pasquale EB: Molecular mechanisms of dendritic spine development and remodeling. Prog Neurobiol 2005;75:161–205.
  19. Sekino Y, Kojima N, Shirao T: Role of actin cytoskeleton in dendritic spine morphogenesis. Neurochem Int 2007;51:92–104.
  20. Pujol F, Kitabgi P, Boudin H: The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons. J Cell Sci 2005;118:1071–1080.
  21. Chen TJ, Gehler S, Shaw AE, Bamburg JR, Letourneau PC: Cdc42 participates in the regulation of ADF/cofilin and retinal growth cone filopodia by brain derived neurotrophic factor. J Neurobiol 2006;66:103–114.
  22. Charych EI, Akum BF, Goldberg JS, Jornsten RJ, Rongo C, Zheng JQ, Firestein BL: Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD 95. J Neurosci 2006;26:10164–10176.
  23. Ramakers GJ: Rho proteins, mental retardation and the cellular basis of cognition. Trends Neurosci 2002;25:191–199.
  24. Pokorny J, Yamamoto T: Postnatal ontogenesis of hippocampal CA1 area in rats. 2. Development of ultrastructure in stratum lacunosum and moleculare. Brain Res Bull 1981;7:121–130.
  25. Gibb R, Kolb B: A method for vibratome sectioning of Golgi-Cox stained whole rat brain. J Neurosci Methods 1998;79:1–4.
  26. Scholl D: Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 1953;87:387–406.

    External Resources

  27. Rasband W: Image J, US National Institutes of Health, Bethesda, Maryland, USA. http://rsbinfonihgov/ij/ 1997–2008.
  28. Spruceton N: Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 2008;9.
  29. Tran PV, Carlson ES, Fretham SJ, Georgieff MK: Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats. J Nutr 2008;138:2495–2501.
  30. Tang BL: Inhibitors of neuronal regeneration: Mediators and signaling mechanisms. Neurochem Int 2003;42:189–203.
  31. Chen H, Firestein BL: RhoA regulates dendrite branching in hippocampal neurons by decreasing cypin protein levels. J Neurosci 2007;27:8378–8386.
  32. Rihn LL, Claiborne BJ: Dendritic growth and regression in rat dentate granule cells during late postnatal development. Brain Res Dev Brain Res 1990;54:115–124.
  33. Taylor EM, Morgan EH: Developmental changes in transferrin and iron uptake by the brain in the rat. Brain Res Dev Brain Res 1990;55:35–42.
  34. Blanpied TA, Scott DB, Ehlers MD: Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics. Neurobiol Aging 2003;24:1095–1104.
  35. Carlson ES, Tkac I, Magid R, O’Connor MB, Andrews NC, Schallert T, Gunshin H, Georgieff MK, Petryk A: Iron is essential for neuron development and memory function in mouse hippocampus. J Nutr 2009;139:672–679.
  36. Schmidt AT, Waldow KJ, Grove WM, Salinas JA, Georgieff MK: Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat. Behav Neurosci 2007;121:475–482.
  37. Burden MJ, Westerlund AJ, Armony-Sivan R, Nelson CA, Jacobson SW, Lozoff B, Angelilli ML, Jacobson JL: An event-related potential study of attention and recognition memory in infants with iron-deficiency anemia. Pediatrics 2007;120:e336–e345.
  38. Tran PV, Fretham SJ, Carlson ES, Georgieff MK: Long-term reduction of hippocampal brain-derived neurotrophic factor activity after fetal-neonatal iron deficiency in adult rats. Pediatr Res 2009;65:493–498.
  39. Malenka RC, Nicoll RA: Long-term potentiation – a decade of progress? Science 1999;285:1870–1874.
  40. Tapia-Arancibia L, Rage F, Givalois L, Arancibia S: Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 2004;25:77–107.
  41. Baudouin SJ, Pujol F, Nicot A, Kitabgi P, Boudin H: Dendrite-selective redistribution of the chemokine receptor CXCR4 following agonist stimulation. Mol Cell Neurosci 2006;33:160–169.
  42. Luo Y, Lathia J, Mughal M, Mattson MP: SDF1α/CXCR4 signaling, via ERKs and the transcription factor Egr1, induces expression of a 67-kDa form of glutamic acid decarboxylase in embryonic hippocampal neurons. J Biol Chem 2008;283:24789–24800.
  43. Li Z, Alzenman, C, Holis, C: Regulation of rho GTPases by crosstalk and neuronal activity in vivo. Neuron 2002;33:741–750.
  44. Hodgkin AL: A note on conduction velocity. J Physiol 1954;125:221–224.
  45. Harris KM, Kater SB: Dendritic spines: Cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci 1994;17:341–371.
  46. Wiens KM, Lin H, Liao D: Rac1 induces the clustering of AMPA receptors during spinogenesis. J Neurosci 2005;25:10627–10636.
  47. Yang Y, Wang XB, Frerking M, Zhou Q: Spine expansion and stabilization associated with long-term potentiation. J Neurosci 2008;28:5740–5751.
  48. Hensch TK: Critical period regulation. Annu Rev Neurosci 2004;27:549–579.
  49. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE: DNA methylationrelated chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003;302:890–893.
  50. Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC: Epigenetics in the nervous system. J Neurosci 2008;28:11753–11759.
  51. Lubin FD, Roth TL, Sweatt JD: Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 2008;28:10576–10586.

 goto top of outline Author Contacts

Michael K. Georgieff, MD
Department of Pediatrics
D-136 Mayo Building, MMC 39, 420 Delaware St. SE Minneapolis, MN 55455 (USA)
Tel. +1 612 626 0644, Fax +1 612 624 8176, E-Mail georg001@umn.edu


 goto top of outline Article Information

Received: February 23, 2010
Accepted after revision: April 26, 2010
Published online: August 6, 2010
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 2, Number of References : 51


 goto top of outline Publication Details

Developmental Neuroscience

Vol. 32, No. 3, Year 2010 (Cover Date: August 2010)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65–P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.



 goto top of outline Author Contacts

Michael K. Georgieff, MD
Department of Pediatrics
D-136 Mayo Building, MMC 39, 420 Delaware St. SE Minneapolis, MN 55455 (USA)
Tel. +1 612 626 0644, Fax +1 612 624 8176, E-Mail georg001@umn.edu


 goto top of outline Article Information

Received: February 23, 2010
Accepted after revision: April 26, 2010
Published online: August 6, 2010
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 2, Number of References : 51


 goto top of outline Publication Details

Developmental Neuroscience

Vol. 32, No. 3, Year 2010 (Cover Date: August 2010)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Degano AL, Pasterkamp RJ, Ronnett GV: MeCP2 deficiency disrupts axonal guidance, fasciculation, and targeting by altering semaphorin 3F function. Mol Cell Neurosci 2009;42:243–254.
  2. Bagot RC, van Hasselt FN, Champagne DL, Meaney MJ, Krugers HJ, Joels M: Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiol Learn Mem 2009;92:292–300.
  3. Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joels M, Krugers H: Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 2008;28:6037–6045.
  4. Williams CL: Food for thought: brain, genes, and nutrition. Brain Res 2008;1237:1–4.
  5. Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, Deregnier RA: Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 2004;55:1034–1041.
  6. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW: Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:E51.
  7. Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver SP, Ramey SL, Nelson KG: Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 2002;140:165–170.
  8. Riggins T, Miller NC, Bauer PJ, Georgieff MK, Nelson CA: Electrophysiological indices of memory for temporal order in early childhood: implications for the development of recollection. Dev Sci 2009;12:209–219.
  9. Lozoff B, Jimenez E, Smith JB: Double burden of iron deficiency in infancy and low socioeconomic status: a longitudinal analysis of cognitive test scores to age 19 years. Arch Pediatr Adolesc Med 2006;160:1108–1113.
  10. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T: Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006;64:S34–43; discussion S72–S91.
  11. McEchron MD, Cheng AY, Liu H, Connor JR, Gilmartin MR: Perinatal nutritional iron deficiency permanently impairs hippocampus-dependent trace fear conditioning in rats. Nutr Neurosci 2005;8:195–206.
  12. Gewirtz JC, Hamilton KL, Babu MA, Wobken JD, Georgieff MK: Effects of gestational iron deficiency on fear conditioning in juvenile and adult rats. Brain Res 2008;1237:195–203.
  13. Jorgenson LA, Wobken JD, Georgieff MK: Perinatal iron deficiency alters apical dendritic growth in hippocampal CA1 pyramidal neurons. Dev Neurosci 2003;25:412–420.
  14. Jorgenson LA, Sun M, O’Connor M, Georgieff MK: Fetal iron deficiency disrupts the maturation of synaptic function and efficacy in area CA1 of the developing rat hippocampus. Hippocampus 2005;15:1094–1102.
  15. Rao R, Tkac I, Townsend EL, Gruetter R, Georgieff MK: Perinatal iron deficiency alters the neurochemical profile of the developing rat hippocampus. J Nutr 2003;133:3215–3221.
  16. Carlson ES, Stead JD, Neal CR, Petryk A, Georgieff MK: Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus. Hippocampus 2007;17:679–691.
  17. Ackermann M, Matus A: Activity-induced targeting of profilin and stabilization of dendritic spine morphology. Nat Neurosci 2003;6:1194–1200.
  18. Ethell IM, Pasquale EB: Molecular mechanisms of dendritic spine development and remodeling. Prog Neurobiol 2005;75:161–205.
  19. Sekino Y, Kojima N, Shirao T: Role of actin cytoskeleton in dendritic spine morphogenesis. Neurochem Int 2007;51:92–104.
  20. Pujol F, Kitabgi P, Boudin H: The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons. J Cell Sci 2005;118:1071–1080.
  21. Chen TJ, Gehler S, Shaw AE, Bamburg JR, Letourneau PC: Cdc42 participates in the regulation of ADF/cofilin and retinal growth cone filopodia by brain derived neurotrophic factor. J Neurobiol 2006;66:103–114.
  22. Charych EI, Akum BF, Goldberg JS, Jornsten RJ, Rongo C, Zheng JQ, Firestein BL: Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD 95. J Neurosci 2006;26:10164–10176.
  23. Ramakers GJ: Rho proteins, mental retardation and the cellular basis of cognition. Trends Neurosci 2002;25:191–199.
  24. Pokorny J, Yamamoto T: Postnatal ontogenesis of hippocampal CA1 area in rats. 2. Development of ultrastructure in stratum lacunosum and moleculare. Brain Res Bull 1981;7:121–130.
  25. Gibb R, Kolb B: A method for vibratome sectioning of Golgi-Cox stained whole rat brain. J Neurosci Methods 1998;79:1–4.
  26. Scholl D: Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 1953;87:387–406.

    External Resources

  27. Rasband W: Image J, US National Institutes of Health, Bethesda, Maryland, USA. http://rsbinfonihgov/ij/ 1997–2008.
  28. Spruceton N: Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 2008;9.
  29. Tran PV, Carlson ES, Fretham SJ, Georgieff MK: Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats. J Nutr 2008;138:2495–2501.
  30. Tang BL: Inhibitors of neuronal regeneration: Mediators and signaling mechanisms. Neurochem Int 2003;42:189–203.
  31. Chen H, Firestein BL: RhoA regulates dendrite branching in hippocampal neurons by decreasing cypin protein levels. J Neurosci 2007;27:8378–8386.
  32. Rihn LL, Claiborne BJ: Dendritic growth and regression in rat dentate granule cells during late postnatal development. Brain Res Dev Brain Res 1990;54:115–124.
  33. Taylor EM, Morgan EH: Developmental changes in transferrin and iron uptake by the brain in the rat. Brain Res Dev Brain Res 1990;55:35–42.
  34. Blanpied TA, Scott DB, Ehlers MD: Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics. Neurobiol Aging 2003;24:1095–1104.
  35. Carlson ES, Tkac I, Magid R, O’Connor MB, Andrews NC, Schallert T, Gunshin H, Georgieff MK, Petryk A: Iron is essential for neuron development and memory function in mouse hippocampus. J Nutr 2009;139:672–679.
  36. Schmidt AT, Waldow KJ, Grove WM, Salinas JA, Georgieff MK: Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat. Behav Neurosci 2007;121:475–482.
  37. Burden MJ, Westerlund AJ, Armony-Sivan R, Nelson CA, Jacobson SW, Lozoff B, Angelilli ML, Jacobson JL: An event-related potential study of attention and recognition memory in infants with iron-deficiency anemia. Pediatrics 2007;120:e336–e345.
  38. Tran PV, Fretham SJ, Carlson ES, Georgieff MK: Long-term reduction of hippocampal brain-derived neurotrophic factor activity after fetal-neonatal iron deficiency in adult rats. Pediatr Res 2009;65:493–498.
  39. Malenka RC, Nicoll RA: Long-term potentiation – a decade of progress? Science 1999;285:1870–1874.
  40. Tapia-Arancibia L, Rage F, Givalois L, Arancibia S: Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 2004;25:77–107.
  41. Baudouin SJ, Pujol F, Nicot A, Kitabgi P, Boudin H: Dendrite-selective redistribution of the chemokine receptor CXCR4 following agonist stimulation. Mol Cell Neurosci 2006;33:160–169.
  42. Luo Y, Lathia J, Mughal M, Mattson MP: SDF1α/CXCR4 signaling, via ERKs and the transcription factor Egr1, induces expression of a 67-kDa form of glutamic acid decarboxylase in embryonic hippocampal neurons. J Biol Chem 2008;283:24789–24800.
  43. Li Z, Alzenman, C, Holis, C: Regulation of rho GTPases by crosstalk and neuronal activity in vivo. Neuron 2002;33:741–750.
  44. Hodgkin AL: A note on conduction velocity. J Physiol 1954;125:221–224.
  45. Harris KM, Kater SB: Dendritic spines: Cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci 1994;17:341–371.
  46. Wiens KM, Lin H, Liao D: Rac1 induces the clustering of AMPA receptors during spinogenesis. J Neurosci 2005;25:10627–10636.
  47. Yang Y, Wang XB, Frerking M, Zhou Q: Spine expansion and stabilization associated with long-term potentiation. J Neurosci 2008;28:5740–5751.
  48. Hensch TK: Critical period regulation. Annu Rev Neurosci 2004;27:549–579.
  49. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE: DNA methylationrelated chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003;302:890–893.
  50. Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC: Epigenetics in the nervous system. J Neurosci 2008;28:11753–11759.
  51. Lubin FD, Roth TL, Sweatt JD: Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 2008;28:10576–10586.