Skip to main content

Advertisement

SpringerLink
Log in

Downregulation of dopamine D1 receptors and increased neuronal apoptosis upon ethanol and PTZ exposure in prenatal rat cortical and hippocampal neurons

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

An Erratum to this article was published on 27 June 2014

Abstract

The objective of this study was to evaluate the effect of ethanol and pentylenetetrazol (PTZ) on the expression of dopamine receptors (D1R) and to observe the apoptotic neurodegeneration in prenatal rat cortical and hippocampal neurons at gestational days (GD) 17.5. In the present study, ethanol (100 mM) and PTZ (15 mM) were exposed to the prenatal rat cortical and hippocampal neuronal cell cultures for 1 h. For mRNA RT-PCR and for protein Western blot analysis was done to elucidate D1R, Bax, Bak, Bcl-2 and cleaved caspase-3 expression upon ethanol and PTZ exposure in neuronal cell cultures. Furthermore, ethanol and PTZ-induced apoptotic neurodegeneration was also observed using TUNEL staining and propidium iodide (PI) used as counter stain under confocal microscopy. The results of present study showed that ethanol and PTZ exposure significantly decreased D1R expression and induced neuronal death by significantly increasing the expression of pro-apoptotic Bax, Bak and decreasing anti-apoptotic protein Bcl-2 leading to the apoptosis by increasing cleaved caspase-3 expression in cortical and hippocampal primary neuronal cell cultures. Our findings indicated that ethanol and PTZ exposure to the prenatal neurons showed not only downregulation of D1R but also causes neuronal apoptosis in the developing rat brain. Further, this explains the possibility of higher risk of developmental disturbances and malformations during early developmental stage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Riley EP, McGee CL (2005) Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med 230:357–365

    CAS  Google Scholar 

  2. Olney JW (2002) New insights and new issues in developmental neurotoxicology. Neurotoxicology 23:659–668

    Article  CAS  PubMed  Google Scholar 

  3. Guerri C (1998) Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res 22:304–312

    Article  CAS  PubMed  Google Scholar 

  4. Coles CD, Platzman KA, Raskind-Hood CL, Brown RT, Falek A, Smith IE (1997) A comparison of children affected by prenatal alcohol exposure and attention deficit, hyperactivity disorder. Alcohol Clin Exp Res 21:150–161

    Article  CAS  PubMed  Google Scholar 

  5. O’Leary CM (2004) Fetal alcohol syndrome: diagnosis, epidemiology, and developmental outcomes. J Paediatr Child Health 40:2–7

    Article  PubMed  Google Scholar 

  6. O’Malley KD, Nanson J (2002) Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder. Can J Psychiatry 47:349–354

    PubMed  Google Scholar 

  7. Abel EL, Reddy PP (1997) Prenatal high saturated fat diet modifies behavioral effects of prenatal alcohol exposure in rats. Alcohol 14:25–29

    Article  CAS  PubMed  Google Scholar 

  8. Hausknecht KA, Acheson A, Farrar AM, Kieres AK, Shen RY, Richards JB et al (2005) Prenatal alcohol exposure causes attention deficits in male rats. Behav Neurosci 119:302–310

    Article  CAS  PubMed  Google Scholar 

  9. Barbier E, Houchi H, Warnault V, Pierrefiche O, Daoust M, Naassila M (2009) Effects of prenatal and postnatal maternal ethanol on offspring response to alcohol and psychostimulants in long evans rats. Neuroscience 161:427–440

    Article  CAS  PubMed  Google Scholar 

  10. Shen RY, Hannigan JH, Chiodo LA (1995) The effects of chronic amphetamine treatment on prenatal ethanol-induced changes in dopamine receptor function: electrophysiological findings. J Pharmacol Exp Ther 274:1054–1060

    CAS  PubMed  Google Scholar 

  11. Goodlett CR, Horn KH (2001) Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Res Health 25:175–184

    CAS  PubMed  Google Scholar 

  12. Becker A, Grecksch G, Thiemann W, Hollt V (2000) Pentylenetetrazol-kindling modulates stimulated dopamine release in the nucleus accumbens of rats. Pharmacol Biochem Behav 66:425–428

    Article  CAS  PubMed  Google Scholar 

  13. Bozzi Y, Vallone D, Borrelli E (2000) Neuroprotective role of dopamine against hippocampal cell death. J Neurosci 20:8643–8649

    CAS  PubMed  Google Scholar 

  14. Turski WA, Cavalheiro EA, Ikonomidou C, Bortolotto ZA, Klockgether T, Turski L (1990) Dopamine control of seizure propagation: intranigral dopamine D1 agonist SKF-38393 enhances susceptibility to seizures. Synapse 5:113–119

    Article  CAS  PubMed  Google Scholar 

  15. Davids E, Zhang K, Tarazi FI, Baldessarini RJ (2003) Animal models of attention-deficit hyperactivity disorder. Brain Res Brain Res Rev 42:1–21

    Article  PubMed  Google Scholar 

  16. Denney CB (2001) Stimulant effects in attention deficit hyperactivity disorder: theoretical and empirical issues. J Clin Child Psychol 30:98–109

    Article  CAS  PubMed  Google Scholar 

  17. Tupala E, Hall H, Halonen P, Tiihonen J (2004) Cortical dopamine D2 receptors in type 1 and 2 alcoholics measured with human whole hemisphere autoradiography. Synapse 54:129–137

    Article  CAS  PubMed  Google Scholar 

  18. Hall H, Sedvall G, Magnusson O, Kopp J, Halldin C, Farde L (1994) Distribution of D1- and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology 11:245–256

    Article  CAS  PubMed  Google Scholar 

  19. Hartman DS, Lanau F (1997) Diversity of dopamine receptors: new molecular and pharmacological developments. Pol J Pharmacol 49:191–199

    CAS  PubMed  Google Scholar 

  20. Naseer MI, Ullah I, Al-Qahtani MH, Karim S, Ullah N, Ansari SA et al (2013) Decreased GABABR expression and increased neuronal cell death in developing rat brain after PTZ-induced seizure. Neurol Sci 34:497–503

    Article  PubMed  Google Scholar 

  21. Naseer MI, Shupeng L, Kim MO (2009) Maternal epileptic seizure induced by pentylenetetrazol: apoptotic neurodegeneration and decreased GABAB1 receptor expression in prenatal rat brain. Mol Brain 2:20

    Article  PubMed Central  PubMed  Google Scholar 

  22. Lee HY, Naha N, Li SP, Jo MJ, Naseer MI, Park MS et al (2008) In vivo and in vitro ethanol exposure in prenatal rat brain: GABA(B) receptor modulation on dopamine D(1) receptor and protein kinase A. Synapse 62:534–543

    Article  CAS  PubMed  Google Scholar 

  23. Ullah N, Naseer MI, Ullah I, Kim TH, Lee HY, Kim MO (2013) Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain. Neurol Sci 15:15

    Google Scholar 

  24. Birioukova LM, Midzyanovskaya IS, Lensu S, Tuomisto L, van Luijtelaar G (2005) Distribution of D1-like and D2-like dopamine receptors in the brain of genetic epileptic WAG/Rij rats. Epilepsy Res 63:89–96

    Article  CAS  PubMed  Google Scholar 

  25. Shen RY, Chiodo LA (1993) The effects of in utero ethanol administration on the electrophysiological activity of rat nigrostriatal dopaminergic neurons. Brain Res 624:216–222

    Article  CAS  PubMed  Google Scholar 

  26. Shen RY, Hannigan JH, Kapatos G (1999) Prenatal ethanol reduces the activity of adult midbrain dopamine neurons. Alcohol Clin Exp Res 23:1801–1807

    Article  CAS  PubMed  Google Scholar 

  27. Randall S, Hannigan JH (1999) In utero alcohol and postnatal methylphenidate: locomotion and dopamine receptors. Neurotoxicol Teratol 21:587–593

    Article  CAS  PubMed  Google Scholar 

  28. Brus R, Felinska W, Rykaczewska M, Kostrzewa RM, Szkilnik R, Plech A (1995) Prenatal ethanol diminishes reactivity of presumed dopamine D3 receptors in rats. Pol J Pharmacol 47:109–114

    CAS  PubMed  Google Scholar 

  29. Boggan WO, Xu W, Shepherd CL, Middaugh LD (1996) Effects of prenatal ethanol exposure on dopamine systems in C57BL/6 J mice. Neurotoxicol Teratol 18:41–48

    Article  CAS  PubMed  Google Scholar 

  30. Vasconcelos SM, Macedo DS, Lima LO, Sousa FC, Fonteles MM, Viana GS (2003) Effect of one-week ethanol treatment on monoamine levels and dopaminergic receptors in rat striatum. Braz J Med Biol Res 36:503–509

    Article  CAS  PubMed  Google Scholar 

  31. Noble EP (1996) Alcoholism and the dopaminergic system: a review. Addict Biol 1:333–348

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the research facility provided by the Center of Excellence in Genomic Medicine and Research (CEGMR), and DSR (HiCi/1432/6-1), King Abdulaziz University Jeddah, Saudi Arabia.

Conflict of interest

There is no conflict of interest regarding this article.

Author information

Authors and Affiliations

  1. Center of Excellence in Genomic Medicine and Research (CEGMR), King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Muhammad Imran Naseer, Mahmood Rasool, Shakeel Ahmed Ansari, Adeel Gulzar Chaudhary & Mohammed H. Al-Qahtani

  2. Division of Life Science, College of Natural Sciences and Applied Life Science (Brain Korea 21), Gyeongsang National University, Chinju, 660-701, Republic of Korea

    Ikram Ullah

  3. King Fahd Medical Research Center (KFMRC), King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia

    Ishfaq Ahmed Sheikh & Fehmida Bibi

Authors
  1. Muhammad Imran Naseer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ikram Ullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahmood Rasool
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shakeel Ahmed Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ishfaq Ahmed Sheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fehmida Bibi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adeel Gulzar Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammed H. Al-Qahtani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammad Imran Naseer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Naseer, M.I., Ullah, I., Rasool, M. et al. Downregulation of dopamine D1 receptors and increased neuronal apoptosis upon ethanol and PTZ exposure in prenatal rat cortical and hippocampal neurons. Neurol Sci 35, 1681–1688 (2014). https://doi.org/10.1007/s10072-014-1812-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-014-1812-7

Keywords

Search

Navigation