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Neonatal dopamine depletion induces changes in morphogenesis and gene expression in the developing cortex

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Abstract

The mesocorticolimbic dopamine (DA) system is implicated in mental health disorders affecting attention, impulse inhibition and other cognitive functions. It has also been involved in the regulation of cortical morphogenesis. The present study uses focal injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of BALB/c mice to examine morphological, behavioral and transcriptional responses to selective DA deficit in the fronto-parietal cortex. Mice that received injections of 6-OHDA on postnatal day 1 (PND1) showed reduction in DA levels in their cortices at PND7. Histological analysis at PND120 revealed increased fronto-cortical width, but decreased width of somatosensory parietal cortex. Open field object recognition suggested impaired response inhibition in adult mice after 6-OHDA treatment. Transcriptional analyses using 17K mouse microarrays showed that such lesions caused up-regulation of 100 genes in the cortex at PND7. Notably, among these genes are Sema3A which plays a repulsive role in axonal guidance, RhoD which inhibits dendritic growth and tubulin β5 microtubule subunit. In contrast, 127 genes were down-regulated, including CCTε and CCTζ that play roles in actin and tubulin folding. Thus, neonatal DA depletion affects transcripts involved in control of cytoskeletal formation and pathway finding, instrumental for normal differentiation and synaptogenesis. The observed gene expression changes are consistent with histological cortical and behavioral impairments in the adult mice treated with 6-OHDA on PND1. Our results point towards specific molecular targets that might be involved in disease process mediated by altered developmental DA regulation.

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References

  • Arakawa Y, H Bito, T Furuyashiki, T Tsuji, S Takemoto-Kimura, K Kimura, K Nozaki, N Hashimoto and S Narumiya (2003) Control of axon elongation via an SDF-1alpha/Rho/ mDia pathway in cultured cerebellar granule neurons.J. Cell Biol. 161, 381–391.

    Article  PubMed  CAS  Google Scholar 

  • Archer T, W Danysz, A Fredriksson, G Jonsson, J Luthman E Sundstrom and A Teiling (1988) Neonatal 6-hydroxydo-pamine-induced dopamine depletions: motor activity and performance in maze learning.Pharmacol. Biochem. Behav. 31, 357–364.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, JB Taylor and MC Cunningham (2000) Convergence and plasticity of monoaminergic systems in the medial pre-frontal cortex during the postnatal period: implications for the development of psychopathology.Cereb. Cortex 10, 1014–1027.

    Article  PubMed  CAS  Google Scholar 

  • Berger B, P Gaspar and C Verney (1991) Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates.Trends Neurosci. 14, 21–27.

    Article  PubMed  CAS  Google Scholar 

  • Berger-Sweeney J and CF Hohmann (1997) Behavioral consequences of abnormal cortical development: insights into developmental disabilities.Behav. Brain Res. 86, 121–142.

    Article  PubMed  CAS  Google Scholar 

  • Berger-Sweeney J, M Libbey, J Arters, M Junagadhwalla and CF Hohmann (1998) Neonatal monoaminergic depletion in mice(Mus. musculus) improves performance of a novel odor discrimination task.Behav. Neurosci. 112, 1318–1326.

    Article  PubMed  CAS  Google Scholar 

  • Blue ME and ME Molliver (1987) 6-Hydroxydopamine induces serotonergic axon sprouting in cerebral cortex of newborn rat.Brain Res. 429, 255–269.

    PubMed  CAS  Google Scholar 

  • Blue ME, RS Erzurumlu and S Jhaveri (1991) A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex.Cereb. Cortex 1, 380–389.

    Article  PubMed  CAS  Google Scholar 

  • Boylan CB, CA Bennett-Clarke, RS Crissman, RD Mooney and RW Rhoades (2000) Clorgyline treatment elevates cortical serotonin and temporarily disrupts the vibrissae-related pattern in rat somatosensory cortex.J. Comp. Neurol. 427, 139–149.

    Article  PubMed  CAS  Google Scholar 

  • Bradke F and CG Dotti (1999) The role of local actin instability in axon formation.Science 283, 1931–1934.

    Article  PubMed  CAS  Google Scholar 

  • Brazma A, P Hingamp, J Quackenbush, G Sherlock, P Spellman, C Stoeckert, J Aach, W Ansorge, CA Ball, HC Causton, T Gaasterland, P Glenisson, FC Holstege, IF Kim, V Markowitz, JC Matese, H Parkinson, A Robinson, U Sarkans, S Schulze-Kremer, J Stewart, R Taylor, J Vilo and M Vingron (2001) Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.Nat. Genet. 29, 365–371.

    Article  PubMed  CAS  Google Scholar 

  • Breese GR, DJ Knapp, HE Criswell, SS Moy, ST Papadeas and BL Blake (2005) The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles.Brain Res. Brain Res. Rev. 48, 57–73.

    Article  PubMed  CAS  Google Scholar 

  • Bruno JP, MI Sandstrom, H Arnold and CL Nelson (1998) Age-dependent neurobehavioral plasticity following forebrain dopamine depletions.Dev. Neurosci. 20, 164–179.

    Article  PubMed  CAS  Google Scholar 

  • Burke D, P Gasdaska and L Hartwell (1989) Dominant effects of tubulin overexpression inSaccharomyces cerevisiae.Mol. Cell. Biol. 9, 1049–1059.

    PubMed  CAS  Google Scholar 

  • Chen X, DS Sullivan and TC Huffaker (1994) Two yeast genes with similarity to TCP-1 are required for microtubule and actin functionin vivo.Proc. Natl. Acad. Sci. USA 91, 9111–9115.

    Article  PubMed  CAS  Google Scholar 

  • Chuang DM, C Hough and VV Senatorov (2005) Glyceraldehyde-3-phosphate dehydrogenase, apoptosis, and neurodegenerative diseases.Annu. Rev. Pharmacol. Toxicol. 45, 269–290.

    Article  PubMed  CAS  Google Scholar 

  • Cohen-Cory S (2002) The developing synapse: construction and modulation of synaptic structures and circuits.Science 298, 770–776.

    Article  PubMed  CAS  Google Scholar 

  • Dennis G Jr, BT Sherman, DA Hosack, J Yang, W Gao, HC Lane and RA Lempicki (2003) DAVID: Database for Annotation, Visualization, and Integrated Discovery.Genome Biol. 4, P3.

    PubMed  Google Scholar 

  • Dent EW, AM Barnes, F Tang and K Kalil (2004) Netrin-1 and semaphorin 3 A promote or inhibit cortical axon branching, respectively, by reorganization of the cytoskeleton.J. Neurosci. 24, 3002–3012.

    Article  PubMed  CAS  Google Scholar 

  • Descarries L, B Lemay, G Doucet and B Berger (1987) Regional and laminar density of the dopamine innervation in adult rat cerebral cortex.Neuroscience 21, 807–824.

    Article  PubMed  CAS  Google Scholar 

  • Dikranian K, MJ Ishimaru, T Tenkova, J Labruyere, YQ Qin C Ikonomidou and JW Olney (2001) Apoptosis in thein vivo mammalian forebrain.Neurobiol. Dis. 8, 359–379.

    Article  PubMed  CAS  Google Scholar 

  • Durston S (2003) A review of the biological bases of ADHD: what have we learned from imaging studies?Ment. Retard. Dev. Disabil. Res. Rev. 9, 184–195.

    Article  PubMed  Google Scholar 

  • Eastwood SL, AJ Law, IP Everall and PJ Harrison (2003) The axonal chemorepellant semaphorin 3A is increased in the cerebellum in schizophrenia and may contribute to its syn-aptic pathology.Mol. Psychiatry 8, 148–155.

    Article  PubMed  CAS  Google Scholar 

  • Foehring RC and NM Lorenzon (1999) Neuromodulation, development and synaptic plasticity.Can. J. Exp. Psychol. 53, 45–61.

    PubMed  CAS  Google Scholar 

  • Fournier AE, F Nakamura, S Kawamoto, Y Goshima RG Kalb and SM Strittmatter (2000) Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse.J. Cell Biol. 149, 411–422.

    Article  PubMed  CAS  Google Scholar 

  • Goshima Y, T Ito, Y Sasaki and F Nakamura (2002) Semaphorins as signals for cell repulsion and invasion.J. Clin. Invest. 109, 993–998.

    PubMed  CAS  Google Scholar 

  • Govek EE, SE Newey and L Van Aelst (2005) The role of the Rho GTPases in neuronal development.Genes Dev. 19, 1–49.

    Article  PubMed  CAS  Google Scholar 

  • Gu Q (2002) Neuromodulatory transmitter systems in cortex and their role in cortical plasticity.Neuroscience 111, 815–835.

    Article  PubMed  CAS  Google Scholar 

  • Guillemot F, Z Molnar, V Tarabykin and A Stoykova (2006) Molecular mechanisms of cortical differentiation.Eur. J. Neurosci. 23, 857–868.

    Article  PubMed  Google Scholar 

  • Harrison PJ and DR Weinberger (2005) Schizophrenia genes, gene expression and neuropathology: on the matter of their convergence.Mol. Psychiatr. 10, 40–68.

    Article  CAS  Google Scholar 

  • Hohmann CF (2003) A morphogenetic role for acetylcholine in mouse cerebral neocortex.Neurosci. Biobehav. Rev. 27, 351–363.

    Article  PubMed  CAS  Google Scholar 

  • Hohmann CF and J Berger-Sweeney (1998) Sexually dimorphic responses to neonatal basal forebrain lesions in mice: II Quantitative assessments of cortical morphology.J. Neurobiol. 5, 401–425.

    CAS  Google Scholar 

  • Hohmann CF, AR Brooks and JT Coyle (1988) Neonatal lesions of the basal forebrain cholinergic neurons result in abnormal cortical development.Brain Res. Dev. Brain Res. 43, 253–264.

    Article  Google Scholar 

  • Hohmann CF, C Richardson, E Pitts and J Bareger-Sweeney (2000) Neonatal 5,7-DHT lesions cause sex specific changes in mouse cortical morphogenesis.Neural Plast. 7, 313–332.

    Article  Google Scholar 

  • Holtz WA and KL O’Malley (2003) Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons.J. Biol. Chem. 278, 19367–19377.

    Article  PubMed  CAS  Google Scholar 

  • Hosack DA, G Dennis Jr, BT Sherman, HC Lane and RA Lempicki (2003) Identifying biological themes within lists of genes with EASE.Genome Biol. 4, R70.

    Article  PubMed  Google Scholar 

  • Jan YN and LY Jan (2003) The control of dendrite development.Neuron 40, 229–242.

    Article  PubMed  CAS  Google Scholar 

  • Johnston MV, C Hohmann and ME Blue (1995) Neurobiology of Rett Syndrome.Neuropediatrics 26, 119–122.

    Article  PubMed  CAS  Google Scholar 

  • Johnston MV, OH Jeon, J Pevsner, ME Blue and S Naidu (2001) Neurobiology of Rett Syndrome: a genetic disorder of synapse development.Brain Dev. 23, 206–213.

    Article  Google Scholar 

  • Joyce JN, PA Frohna and BS Neal-Beliveau (1996) Functional and molecular differentiation of the dopamine system induced by neonatal denervation.Neurosci. Biobehav. Rev. 20, 453–486.

    Article  PubMed  CAS  Google Scholar 

  • Kalsbeek A, RM Buijs, MA Hofman, MA Matthijssen CW Pool and HB Uylings (1987) Effects of neonatal thermal lesioning of the mesocortical dopaminergic projection on the development of the rat prefrontal cortex.Brain Res. 429, 123–132.

    PubMed  CAS  Google Scholar 

  • Kalsbeek A, JP de Bruin, MA Matthijssen and HB Uylings (1989a) Ontogeny of open field activity in rats after neonatal lesioning of the mesocortical dopaminergic projection.Behav. Brain Res. 32, 115–127.

    Article  PubMed  CAS  Google Scholar 

  • Kalsbeek A, MA Matthijssen and HB Uylings (1989b) Morphometric analysis of prefrontal cortical development following neonatal lesioning of the dopaminergic mesocortical projection.Exp. Brain Res. 78, 279–289.

    Article  PubMed  CAS  Google Scholar 

  • Krasnova IN, B Ladenheim, S Jayanthi, J Oyler, TH Moran, MA Huestis and JL Cadet (2001) Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: complex roles for oxygen-based species and temperature regulation.Neuroscience 107, 265–274.

    Article  PubMed  CAS  Google Scholar 

  • Krasnova IN, MT McCoy, B Ladenheim and JL Cadet (2002) cDNA array analysis of gene expression profiles in the stri-ata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine.FASEB J. 16, 1379–1388.

    Article  PubMed  CAS  Google Scholar 

  • Krasnova IN, B Ladenheim and JL Cadet (2005) Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway.FASEB J. 19, 851–853.

    PubMed  CAS  Google Scholar 

  • Kruger RP, J Aurandt and KL Guan (2005) Semaphorins command cells to move.Nat. Rev. Mol. Cell. Biol. 6, 789–800.

    Article  PubMed  CAS  Google Scholar 

  • Li Z, L Van Aelst and HT Cline (2000) Rho GTPases regulate distinct aspects of dendritic arbor growth inXenopus central neuronsin vivo.Nat. Neurosci. 3, 217–225.

    Article  PubMed  CAS  Google Scholar 

  • Luthman J, E Brodin, E Sundstrom and B Wiehager (1990) Studies on brain monoamine and neuropeptide systems after neonatal intracerebroventricular 6-hydroxydopamine treatment.Int. J. Dev. Neurosci. 8, 549–560.

    Article  PubMed  CAS  Google Scholar 

  • Luthman J, M Bassen, A Fredriksson and T Archer (1997) Functional changes induced by neonatal dopamine treatment: effects of dose levels on behavioral parameters.Behav. Brain Res. 82, 213–221.

    Article  PubMed  CAS  Google Scholar 

  • Mick E, J Biederman, SV Faraone, J Sayer and S Kleinman (2002) Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy.J. Am. Acad. Child Adolesc. Psychiatry 41, 378–385.

    Article  Google Scholar 

  • Miller FE, TG Heffner, C Kotake and LS Seiden (1981) Magnitude and duration of hyperactivity following neonatal 6-hydroxydopamine is related to the extent of brain dopamine depletion.Brain Res. 229, 123–132.

    Article  PubMed  CAS  Google Scholar 

  • Molina-Holgado E, KM Dewar, L Grondin, NM van Gelder and TA Reader (1993) Amino acid levels and gamma-aminobutyric acidA receptors in rat neostriatum, cortex, and thalamus after neonatal 6-hydroxydopamine lesion.J. Neurochem. 60, 936–945.

    Article  PubMed  CAS  Google Scholar 

  • Napolitano M, D Centonze, A Calce, B Picconi, S Spiezia A Gulino, G Bernardi and P Calabresi (2002) Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum.Neurobiol. Dis. 10, 387–395.

    Article  PubMed  CAS  Google Scholar 

  • Neal-Beliveau BS and JN Joyce (1999) Timing: a critical determinant of the functional consequences of neonatal 6-OHDA lesions.Neurotox. Teratol. 21, 129–140.

    Article  CAS  Google Scholar 

  • Noailles PA, KG Becker, WH Wood 3rd, D Teichberg and JL Cadet (2003) Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drugin utero.Brain Res. Dev. Brain Res. 147, 153–162.

    Article  PubMed  CAS  Google Scholar 

  • Onteniente B, N Konig, J Sievers, S Jenner, HP Klemm and R Marty (1980) Structural and biochemical changes in rat cerebral cortex after neonatal 6-hydroxdopamine administration.Anat. Embryol. 159, 245–255.

    Article  PubMed  CAS  Google Scholar 

  • Pappas BA, SJ Murtha, GA Park, KT Condon, RM Szirtes, SI Laventure and A Ally (1992) Neonatal brain dopamine depletion and the cortical and behavioral consequences of enriched postweaning environment.Pharmacol. Biochem. Behav. 42, 741–748.

    Article  PubMed  CAS  Google Scholar 

  • Pilpel Y and M Segal (2004) Activation of PKC induces rapid morphological plasticity in dendrites of hippocampal neurons via Rac and Rho-dependent mechanisms.Eur. J. Neurosci. 19, 3151–3164.

    Article  PubMed  Google Scholar 

  • Poucet B (1989) Object exploration, habituation and response to spatial change in rats following septal or medial frontal cortical damage.Behav. Neurosci. 103, 1009–1016.

    Article  PubMed  CAS  Google Scholar 

  • Price DJ, H Kennedy, C Dehay, L Zhou, M Mercier, Y Jossin, AM Goffinet, F Tissir, D Blakey and Z Molnar (2006) The development of cortical connections.Eur. J. Neurosci. 23, 910–920.

    Article  PubMed  Google Scholar 

  • Raedler TJ, MB Knable and DR Weinberger (1998) Schizophrenia as a developmental disorder of the cerebral cortex.Curr. Opin. Neurobiol. 8, 157–161.

    Article  PubMed  CAS  Google Scholar 

  • Raskin LA, BA Shaywitz, GM Anderson, DJ Cohen MH Teicher and J Linakis (1983) Differential effects of selective dopamine, norepinephrine or catecholamine depletion on activity and learning in the developing rat.Pharmacol. Biochem. Behav. 19, 743–749.

    Article  PubMed  CAS  Google Scholar 

  • Ricceri L, A Usiello, A Valanzano, G Calamandrei, K Frick and J Berger-Sweeney (1999) Neonatal192IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.Behav. Neurosci. 113, 1204–1215.

    Article  PubMed  CAS  Google Scholar 

  • Rice D and S Barone Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.Environ. Health Perspect. 108 Suppl. 3, 511–533.

    Article  PubMed  Google Scholar 

  • Roth RM and AJ Saykin (2004) Executive dysfunction in attention-deficit/hyperactivity disorder: cognitive and neuro-imaging findings.Psychiatr. Clin. North Am. 27, 83–96, ix.

    Article  PubMed  Google Scholar 

  • Roullet P and JM Lassalle (1990) Genetic variation, hippocampal mossy fiber distribution, novelty reaction and spatial representation in mice.Behav. Brain Res. 41, 61–70.

    Article  PubMed  CAS  Google Scholar 

  • Shastry BS (2004) Molecular genetics of attention-deficit hyperactivity disorder (ADHD): and update.Neurochem. Int. 44, 469–474.

    Article  PubMed  CAS  Google Scholar 

  • Shenton ME, CC Dickey, M Frumin and RW McCarley (2001) A review of MRI findings in schizophrenia.Schizophr. Res. 49, 1–52.

    Article  PubMed  CAS  Google Scholar 

  • Sherrard RM and AJ Bower (1998) Role of afferents in the development and cell survival of the vertebrate nervous system.Clin. Exp. Pharmacol. Physiol. 25, 487–495.

    Article  PubMed  CAS  Google Scholar 

  • Sherren N and BA Pappas (2005) Selective acetylcholine and dopamine lesions in neonatal rats produce distinct patterns of cortical dendritic atrophy in adulthood.Neuroscience 136, 445–456.

    Article  PubMed  CAS  Google Scholar 

  • Shirvan A, I Ziv, G Fleminger, R Shina, Z He, I Brudo E Melamed and A Barzilai (1999) Semaphorins as mediators of neuronal apoptosis.J. Neurochem. 73, 961–971.

    Article  PubMed  CAS  Google Scholar 

  • Sullivan RM and W Brake (2003) What the rodent cortex can teach us about attention deficit/hyperactivity disorder: the critical role of early deveopmental events on prefrontal function.Behav. Brain Res. 146, 43–55.

    Article  PubMed  Google Scholar 

  • Thinus-Blanc C, E Save, C Rossi-Arnaud, A Tozzi and M Ammassari-Teule (1996) The difference shown by C57BL/6 and DBA/2 inbred mice in detecting spatial novelty are subserved by a different hippocampal and parietal cortex interplay.Behav. Brain Res. 80, 33–40.

    Article  PubMed  CAS  Google Scholar 

  • Valpuesta JM, J Martin-Benito, P Gomez-Puertas, JL Carrascosa and KR Willison (2002) Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT.FEBS Lett. 529, 11–16.

    Article  PubMed  CAS  Google Scholar 

  • Vinh DB and DG Drubin (1994) A yeast TCP-1-like protein is required for actin functionin vivo.Proc. Natl. Acad. Sci. USA 91, 9116–9120.

    Article  PubMed  CAS  Google Scholar 

  • Weinstein B and F Solomon (1990) Phenotypic consequences of tubulin overproduction inSaccharomyces cerevisiae: differences between α-tubulin and β-tubulin.Mol. Cell. Biol. 10, 5295–5304.

    PubMed  CAS  Google Scholar 

  • Wong WT, BE Faulkner-Jones, JR Sanes and RO Wong (2000) Rapid dendritic remodeling in the developing retina: dependence on neurotransmission and reciprocal regulation by Rac and Rho.J. Neurosci. 20, 5024–5036.

    PubMed  CAS  Google Scholar 

  • Woolsey TA and H Van der Loos (1970) The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex.Brain Res. 17, 205–242.

    Article  PubMed  CAS  Google Scholar 

  • Ziv NE and CC Garner (2004) Cellular and molecular mechanisms of presynaptic assembly.Nat. Rev. Neurosci. 5, 385–399.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH/DHHS, 21251, Baltimore, MD, USA

    Irina N. Krasnova, Elizabeth S. Betts, Bruce Ladenheim & Jean Lud Cadet

  2. Department of Biology, Morgan State University, 21251, Baltimore, MD, USA

    Elizabeth S. Betts, Abiola Dada, Akilah Jefferson & Christine F. Hohmann

  3. Gene Expression and Genomics Unit, National Institute on Aging, NIH/DHHS, 21251, Baltimore, MD, USA

    Kevin G. Becker

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  1. Irina N. Krasnova
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  2. Elizabeth S. Betts
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Correspondence to Christine F. Hohmann.

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Krasnova, I.N., Betts, E.S., Dada, A. et al. Neonatal dopamine depletion induces changes in morphogenesis and gene expression in the developing cortex. neurotox res 11, 107–130 (2007). https://doi.org/10.1007/BF03033390

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