Epidermal growth factor (EGF) receptor (ErbB1) signals regulate dopaminergic development and function and are implicated in schizophrenia. We evaluated genetic effects on neurobehavioral changes induced by neonatal EGF administration, using four mouse strains. Subcutaneous EGF administration increased phosphorylation of brain ErbB1 in all strains, although DBA/2 and C57BL/6 mice had lower basal phosphorylation. Neonatal EGF treatment differentially influenced physical and behavioral/cognitive development, depending on mouse strain. Prepulse inhibition was decreased in DBA/2 and C57BL/6 mice but not C3H/He and ddY mice. Locomotor activity was accelerated in DBA/2 mice, but reduced in ddY mice. EGF treatment enhanced fear-learning performance with a tone cue in DBA/2 mice, but decreased performance with tone and context cues in C3H/He and ddY mice, respectively. The strain-dependent behavioral sensitivity was correlated with basal ErbB1 phosphorylation. Genetic components regulating brain ErbB1 signaling strongly influence the direction and strength of behavioral responses stemming from the neonatal neurotrophic perturbation.
Similar content being viewed by others
References
E. D. Adamson J. Meek (1984) ArticleTitleThe ontogeny of epidermal growth factor receptors during mouse development Dev. Biol. 103 62–70 Occurrence Handle10.1016/0012-1606(84)90007-1 Occurrence Handle6325281
T. Alexi F. Hefti (1993) ArticleTitleTrophic actions of transforming growth factor alpha on mesencephalic dopaminergic neurons developing in culture Neuroscience 55 903–918 Occurrence Handle10.1016/0306-4522(93)90307-2 Occurrence Handle7901801
S. Anttila A. Illi O. Kampman K. M. Mattila T. Lehtimaki E. Leinonen (2004) ArticleTitleAssociation of EGF polymorphism with schizophrenia in Finnish men Neuroreport 15 1215–1218 Occurrence Handle10.1097/00001756-200405190-00027 Occurrence Handle15129177
S. G. Anagnostaras S. A. Josselyn P. W. Frankland A. J. Silva (2000) ArticleTitleComputer-assisted behavioral assessment of Pavlovian fear conditioning in mice Learn. Mem. 7 58–72 Occurrence Handle10.1101/lm.7.1.58 Occurrence Handle10706603
H. Baker T. H. Joh D. J. Reis (1980) ArticleTitleGenetic control of number of midbrain dopaminergic neurons in inbred strains of mice: relationship to size and neuronal density of the striatum Proc. Natl. Acad. Sci. USA 77 4369–4373 Occurrence Handle6107905
M. A. Blum (1998) ArticleTitleNull mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra Nature Neurosci. 1 374–377 Occurrence Handle10.1038/1584 Occurrence Handle10196526
D. L. Braff M. A. Geyer (1990) ArticleTitleSensorimotor gating and schizophrenia: human and animal model studies Arch. Gen. Psychiatry 47 181–188 Occurrence Handle2405807
D. L. Braff C. Grillon M. A. Geyer (1992) ArticleTitleGating and habituation of the startle reflex in schizophrenic patients Arch. Gen. Psychiatry 49 206–215 Occurrence Handle1567275
A. E. Bullock B. S. Slobe V. Vazquez A. C. Collins (1997) ArticleTitleInbred mouse strains differ in the regulation of startle and prepulse inhibition of the startle response Behav. Neurosci. 111 1353–1360 Occurrence Handle10.1037/0735-7044.111.6.1353 Occurrence Handle9438803
M. Cannon P. B. Jones R. M. Murray (2002) ArticleTitleObstetric complications and schizophrenia: historical and meta-analytic review Am. J. Psychiatry 159 1080–1092 Occurrence Handle10.1176/appi.ajp.159.7.1080 Occurrence Handle12091183
D. Casper C. Mytilineou M. Blum (1991) ArticleTitleEGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture J. Neurosci. Res. 30 372–381 Occurrence Handle10.1002/jnr.490300213 Occurrence Handle1839162
S. Cohen (1962) ArticleTitleIsolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal J. Biol. Chem. 237 1555–1562 Occurrence Handle13880319
J. N. Crawley J. K. Belknap A. Collins J. C. Crabbe W. Frankel N. Henderson R. J. Hitzemann S. C. Maxson L. L. Miner A. J. Silva J. M. Wehner A. Wynshaw-Boris R. Paylor (1997) ArticleTitleBehavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies Psychopharmacology (Berl) 132 107–124 Occurrence Handle10.1007/s002130050327
S. C. Dulawa M. A. Geyer (1996) ArticleTitlePsychopharmacology of prepulse inhibition in mice Chin. J. Physiol. 39 139–146 Occurrence Handle8955560
G. Ferrari G. Toffano S. D. Skaper (1991) ArticleTitleEpidermal growth factor exerts neuronotrophic effects on dopaminergic and GABAergic CNS neurons: comparison with basic fibroblast growth factor J. Neurosci. Res. 30 493–497 Occurrence Handle10.1002/jnr.490300306 Occurrence Handle1800771
P. W. Frankland S. A. Josselyn S. G. Anagnostaras J. H. Kogan E. Takahashi A. J. Silva (2004) ArticleTitleConsolidation of CS and US representations in associative fear conditioning Hippocampus 14 557–569 Occurrence Handle10.1002/hipo.10208 Occurrence Handle15301434
T. Futamura K. Toyooka S. Iritani K. Niizato R. Nakamura K. Tsuchiya T. Someya A. Kakita H. Takahashi H. Nawa (2002) ArticleTitleAbnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients Mol. Psychiatry 7 673–682 Occurrence Handle10.1038/sj.mp.4001081 Occurrence Handle12192610
T. Futamura A. Kakita M. Tohmi H. Sotoyama H. Takahashi H. Nawa (2003) ArticleTitleNeonatal perturbation of neurotrophic signaling results in abnormal sensorimotor gating and social interaction in adults: implication for epidermal growth factor in cognitive development Mol. Psychiatry 8 19–29 Occurrence Handle10.1038/sj.mp.4001138 Occurrence Handle12556905
P. L. Gendreau J. L. Gariepy J. M. Petitto M. H. Lewis (1997) ArticleTitleD1 dopamine receptor mediation of social and nonsocial emotional reactivity in mice: effects of housing and strain difference in motor activity Behav. Neurosci. 111 424–434 Occurrence Handle10.1037/0735-7044.111.2.424 Occurrence Handle9106681
F. Gomez-Pinilla D. J. Knauer M. Nieto-Sampedro (1988) ArticleTitleEpidermal growth factor receptor immunoreactivity in rat brain. Development and cellular localization Brain. Res. 438 385–390 Occurrence Handle10.1016/0006-8993(88)91369-8 Occurrence Handle3345447
H. Gregory B. M. Preston (1977) ArticleTitleThe primary structure of human urogastrone Int. J. Pept. Protein Res. 9 107–118 Occurrence Handle300079
M. Hadjiconstantinou J. G. Fitkin A. Dalia N. H. Neff (1991) ArticleTitleEpidermal growth factor enhances striatal dopaminergic parameters in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse J. Neurochem. 57 479–482 Occurrence Handle1677029
M. Hanke L. M. Farkas M. Jakob R. Ries J. Pohl A. M. Sullivan (2004) ArticleTitleHeparin-binding epidermal growth factor-like growth factor: a component in chromaffin granules which promotes the survival of nigrostriatal dopaminergic neurones in vitro and in vivo Neuroscience 124 757–766 Occurrence Handle10.1016/j.neuroscience.2003.12.033 Occurrence Handle15026116
L.A. Hilakivi-Clarke T. D. Corduban T. Taira A. Hitri S. Deutsch E. R. Korpi R. Goldberg K. J. Kellar (1995) ArticleTitleAlterations in brain monoamines and GABAA receptors in transgenic mice overexpressing TGF alpha Pharmacol. Biochem. Behav. 50 593–600 Occurrence Handle10.1016/0091-3057(94)00347-5 Occurrence Handle7617706
G. E. Hofmann J. S. Abramowicz (1990) ArticleTitleEpidermal growth factor (EGF) concentrations in amniotic fluid and maternal urine during pregnancy Acta. Obstet. Gynecol. Scand. 69 217–221 Occurrence Handle2220342
M. H. Hsieh K. Liu S. K. Liu M. J. Chiu H. G. Hwu A. C. Chen (2004) ArticleTitleMemory impairment and auditory evoked potential gating deficit in schizophrenia Psychiatry Res. 130 161–169 Occurrence Handle15033186
M. Isono M. Goda H. Kobayashi J. L. Wu (2003) ArticleTitleTGF-alpha overexpression induces astnding epidermal growth factor-like growth factor mRNA expression in neonatal rat brain with hypoxic/ischemic injury Brain Res. 827 130–138
Iwakura, Y., Piao, Y., Mizuno, M., Takei, N., Kakita, A., Takahashi, H., and Nawa, H. (2005). Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson’s disease and its model; neurotrophic implication in nigrostriatal neurons. J. Neurochem. 93: 974–983.
M. R. Kaser J. Lakshmanan D. A. Fisher (1992) ArticleTitleComparison between epidermal growth factor, transforming growth factor-alpha and EGF receptor levels in regions of adult rat brain Mol. Brain Res. 16 316–322 Occurrence Handle10.1016/0169-328X(92)90241-3 Occurrence Handle1337941
N. Kawahara K. Mishima S. Higashiyama N. Taniguchi A. Tamura T. Kirino (1999) ArticleTitleThe gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible: its role in cerebral ischemia J. Cereb. Blood Flow. Metab. 19 307–320 Occurrence Handle10.1097/00004647-199903000-00009 Occurrence Handle10078883
H. I. Kornblum R. J. Hussain J. M. Bronstein C. M. Gall D. C. Lee K. B. Seroogy (1997) ArticleTitlePrenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain J. Comput. Neurol. 380 243–261 Occurrence Handle10.1002/(SICI)1096-9861(19970407)380:2<243::AID-CNE7>3.0.CO;2-3
R. P. Kleshcheva (1988) ArticleTitleThe development of components of the blood–brain barrier in the neocortex of the white rat Arkh. Anat. Gistol. Embriol. 95 22–26
V. Kumari I. Aasen T. Sharma (2004) ArticleTitleSex differences in prepulse inhibition deficits in chronic schizophrenia Schizophr. Res. 69 219–235 Occurrence Handle10.1016/j.schres.2003.09.010 Occurrence Handle15469195
B. K. Lipska D. R. Weinberger (1995) ArticleTitleGenetic variation in vulnerability to the behavioral effects of neonatal hippocampal damage in rats Proc. Natl. Acad. Sci. USA 92 8906–8910 Occurrence Handle7568041
B. K. Lipska H. A. al-Amin D. R. Weinberger (1998) ArticleTitleExcitotoxic lesions of the rat medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage Neuropsychopharmacology 19 451–464 Occurrence Handle10.1016/S0893-133X(98)00045-1 Occurrence Handle9803421
M. J. Marks J. A. Stitzel A. C. Collins (1989) ArticleTitleGenetic influences on nicotine responses Pharmacol. Biochem. Behav. 33 667–678 Occurrence Handle10.1016/0091-3057(89)90406-1 Occurrence Handle2587608
M. Mizuno R. S. Malta SuffixJr T. Nagano H. Nawa (2004) ArticleTitleConditioned place preference and locomotor sensitization following repeated administration of cocaine or methamphetamine in rats treated with EGF during neonatal period Ann. NY Acad. Sci. 1025 612–618 Occurrence Handle10.1196/annals.1316.076 Occurrence Handle15542770
S. O. Moldin I. I. Gottesman (1997) ArticleTitleAt issue: genes, experience, and chance in schizophrenia-positioning for the 21st century Schizophr. Bull. 23 547–561 Occurrence Handle9365994
R. M. Murray S. W. Lewis (1987) ArticleTitleIs schizophrenia a neurodevelopmental disorder? Br. Med. J. 295 681–682
T. Nakagawa M. Sasahara Y. Hayase M. Haneda H. Yasuda R. Kikkawa S. Higashiyama F. Hazama (1998) ArticleTitleNeuronal and glial expression of heparin-binding EGF-like growth factor in central nervous system of prenatal and early-postnatal rat Dev. Brain. Res. 108 263–272 Occurrence Handle10.1016/S0165-3806(98)00057-1
O. Narayan S. Herzog K. Frese H. Scheefers R. Rott (1983) ArticleTitleBehavioral disease in rats caused by immunopathological responses to persistent borna virus in the brain Science 220 1401–1403 Occurrence Handle6602380
H. Nawa M. Takahasi P. H. Patterson (2000) ArticleTitleCytokine and growth factor involvement in schizophrenia-support for the development model Mol. Psychiatry 5 594–603 Occurrence Handle10.1038/sj.mp.4000730 Occurrence Handle11126390
Nawa, H. and Futamura, T. (2003). Animal showing schizophrenia-like abnormality in cognitive behaviors and method of constructing the same. US patent application 20030056232.
P. V. Nguyen T. Abel E. R. Kandel R. Bourtchouladze (2000) ArticleTitleStrain-dependent differences in LTP and hippocampus-dependent memory in inbred mice Learn. Mem. 7 170–179 Occurrence Handle10.1101/lm.7.3.170 Occurrence Handle10837506
E. O’Callaghan P. Sham N. Takei G. Glover R. M. Murray (1991) ArticleTitleSchizophrenia after prenatal exposure to 1957 A2 influenza epidemic Lancet 337 1248–1250 Occurrence Handle10.1016/0140-6736(91)92919-S Occurrence Handle1674062
E. O’Callaghan T. Gibson H. A. Colohan P. Buckley D. G. Walshe C. Larkin J. L. Waddington (1992) ArticleTitleRisk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study Br. Med. J. 305 1256–1259
L. A. Opanashuk R. J. Mark J. Porter D. Damm M. P. Mattson K. B. Seroogy (1999) ArticleTitleHeparin-binding epidermal growth factor-like growth factor in hippocampus: modulation of expression by seizures and anti-excitotoxic action J. Neurosci. 19 33–146
W. Pan A. J. Kastin (1999) ArticleTitleEntry of EGF into brain is rapid and saturable Peptides 20 1091–1098 Occurrence Handle10.1016/S0196-9781(99)00094-7 Occurrence Handle10499427
W. Parzefall E. Kainzbauer H. M. Qin M. Chabicovsky R. Schulte-Hermann (2002) ArticleTitleResponse of isolated hepatocytes from carcinogen sensitive (C3H) and insensitive (C57BL) mice to signals inducing replication or apoptosis Arch. Toxicol. 76 699–706 Occurrence Handle10.1007/s00204-002-0397-8 Occurrence Handle12451446
M. Peracchi F. Bamonti Catena M. Pomati M. De Franceschi G. Scalabrino (2001) ArticleTitleHuman cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor Eur. J. Haematol. 67 123–127 Occurrence Handle10.1034/j.1600-0609.2001.t01-1-00507.x Occurrence Handle11722601
A. Petronis (2004) ArticleTitleThe origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis Biol. Psychiatry 55 965–970 Occurrence Handle10.1016/j.biopsych.2004.02.005 Occurrence Handle15121478
R. G. Phillips J. E. LeDoux (1992) ArticleTitleDifferential contribution of amygdala and hippocampus to cued and contextual fear conditioning Behav. Neurosci. 106 274–285 Occurrence Handle10.1037/0735-7044.106.2.274 Occurrence Handle1590953
M. V. Pletnikov S. A. Rubin M. W. Vogel T. H. Moran K. M. Carbone (2002) ArticleTitleEffects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage. II. Neurochemical alterations and responses to pharmacological treatments Brain. Res. 944 108–123 Occurrence Handle10.1016/S0006-8993(02)02724-5 Occurrence Handle12106671
R. D. Romeo J. A. Fossella H. S. Bateup H. M. Sisti W. G. Brake B. S. McEwen (2004) ArticleTitleMaternal separation suppresses TGFalpha mRNA expression in the prefrontal cortex of male and female neonatal C57BL/6 mice Dev. Brain. Res. 152 73–77 Occurrence Handle10.1016/j.devbrainres.2004.05.007
B. Sacchetti C. A. Lorenzini E. Baldi G. Tassoni C. Bucherelli (1999) ArticleTitleAuditory thalamus, dorsal hippocampus, basolateral amygdala, and perirhinal cortex role in the consolidation of conditioned freezing to context and to acoustic conditioned stimulus in the rat J. Neurosci. 19 9570–9578 Occurrence Handle10531459
M. Salvatore S. Morzunov M. Schwemmle W. I. Lipkin (1997) ArticleTitleBorna disease virus in brains of North American and European people with schizophrenia and bipolar disorder. Bornavirus Study Group Lancet 349 1813–1814 Occurrence Handle10.1016/S0140-6736(05)61693-5 Occurrence Handle9269221
R. P. Schaudies J. P. Johnson (1993) ArticleTitleIncreased soluble EGF after ischemia is accompanied by a decrease in membrane-associated precursors Am. J. Physiol. 264 F523–F531 Occurrence Handle8456964
K. B. Seroogy S Numan C. M. Gall D. C. Lee H. I. Kornblum (1994) ArticleTitleExpression of EGF receptor mRNA in rat nigrostriatal system NeuroReport 6 105–108 Occurrence Handle7703395
L. Shi S. H. Fatemi R.W. Sidwell P. H. Patterson (2003) ArticleTitleMaternal influenza infection causes marked behavioral and pharmacological changes in the offspring J. Neurosci. 23 297–302 Occurrence Handle12514227
M. Sibilia J. P. Steinbach L. Stingl A. Aguzzi E. F. Wagner (1998) ArticleTitleA strain-independent postnatal neurodegeneration in mice lacking the EGF receptor EMBO J. 17 719–731 Occurrence Handle10.1093/emboj/17.3.719 Occurrence Handle9450997
H. Stefansson E. Sigurdsson V. Steinthorsdottir S. Bjornsdottir T. Sigmundsson S. Ghosh J. Brynjolfsson S. Gunnarsdottir O. Ivarsson T. T. Chou O. Hjaltason B. Birgisdottir H. Jonsson V. G. Gudnadottir E. Gudmundsdottir A. Bjornsson B. Ingvarsson A Ingason S. Sigfusson H. Hardardottir R. P. Harvey D. Lai M. Zhou D. Brunner V. Mutel A. Gonzalo G Lemke J Sainz G Johannesson T Andresson D Gudbjartsson A Manolescu M. L. Frigge M. E. Gurney A. Kong J. R. Gulcher H. Petursson K. Stefansson (2002) ArticleTitleNeuregulin 1 and susceptibility to schizophrenia Am. J. Hum. Genet. 71 877–892 Occurrence Handle10.1086/342734 Occurrence Handle12145742
E. V. Sullivan P. K. Shear R. B. Zipursky H. J. Sagar A. Pfefferbaum (1997) ArticleTitlePatterns of content, contextual, and working memory impairments in schizophrenia and nonamnesic alcoholism Neuropsychology 11 195–206 Occurrence Handle10.1037/0894-4105.11.2.195 Occurrence Handle9110327
N. R. Swerdlow M. A. Geyer (1998) ArticleTitleUsing an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia Schizophr. Bull. 24 285–301 Occurrence Handle9613626
N. Tanaka M. Sasahara M. Ohno S. Higashiyama Y. Hayase M. Shimada (1999) ArticleTitleHeparin-binding epidermal growth factor-like growth factor mRNA expression in neonatal rat brain with hypoxic/ischemic injury Brain. Res. 827 130–138 Occurrence Handle10.1016/S0006-8993(99)01319-0 Occurrence Handle10320701
M. Tom-Moy T. Barka (1981) ArticleTitleEpidermal growth factor in the submandibular glands of inbred mice Am. J. Anat. 160 267–276 Occurrence Handle10.1002/aja.1001600305 Occurrence Handle6971571
L. Tong H. Shen V. M. Perreau S. R. Balaz C. W. Cotman (2001) ArticleTitleEffects of exercise on gene-expression profile in the rat hippocampus Neurobiol. Dis. 8 1046–1056 Occurrence Handle10.1006/nbdi.2001.0427 Occurrence Handle11741400
M. W. Varner G. A. Dildy C. Hunter D. J. Dudley S. L. Clark M. D. Mitchell (1996) ArticleTitleAmniotic fluid epidermal growth factor levels in normal and abnormal pregnancies J. Soc. Gynecol. Investig. 3 17–19 Occurrence Handle10.1016/1071-5576(95)00044-5 Occurrence Handle8796801
L. L. Ventrella (1993) ArticleTitleEffect of intracerebroventricular infusion of epidermal growth factor in rats hemitransected in the nigro-striatal pathway J. Neurosurg. Sci. 37 1–8 Occurrence Handle8103556
J. Waddell C. Dunnett W. A. Falls (2004) ArticleTitleC57BL/6J and DBA/2J mice differ in extinction and renewal of extinguished conditioned fear Behav. Brain. Res. 154 567–576 Occurrence Handle10.1016/j.bbr.2004.03.025 Occurrence Handle15313046
J. M. Wehner R. A. Radcliffe S. T. Rosmann S. C. Christensen D. L. Rasmussen D. W. Fulker M. Wiles (1997) ArticleTitleQuantitative trait locus analysis of contextual fear conditioning in mice Nat. Genet. 17 331–334 Occurrence Handle9354800
D. R. Weinberger (1987) ArticleTitleImplications of normal brain development for the pathogenesis of schizophrenia Arch. Gen. Psychiatry 44 660–669 Occurrence Handle3606332
A. Zocchi C. Orsini S. Cabib S. Puglisi-Allegra (1998) ArticleTitleParallel strain-dependent effect of amphetamine on locomotor activity and dopamine release in the nucleus accumbens: an in vivo study in mice Neuroscience 82 521–528 Occurrence Handle10.1016/S0306-4522(97)00276-5 Occurrence Handle9466458
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tohmi, M., Tsuda, N., Mizuno, M. et al. Distinct Influences of Neonatal Epidermal Growth Factor Challenge on Adult Neurobehavioral Traits in Four Mouse Strains. Behav Genet 35, 615–629 (2005). https://doi.org/10.1007/s10519-005-5357-7
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10519-005-5357-7