Effects of neonatal and prepubertal hormonal manipulations upon estrogen neuroprotection of the nigrostriatal dopaminergic system within female and male mice

Neuroscience. 2005;130(2):369-82. doi: 10.1016/j.neuroscience.2004.09.033.


Estrogen (E) can function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA) neurotoxicity in female, but not male, mice. In the present report we examined whether the organizational effects of gonadal steroid hormones, as exerted in the early postnatal period, or developmental effects, as exerted during the pubertal period, would contribute to this sexually dimorphic neuroprotectant action of E. Neonatal gonadectomy and treatment with testosterone of female mice, retained the ability to show an E neuroprotectant response when tested as adults. However, females not treated with gonadal steroids failed to show an E-dependent neuroprotectant response. Neonatal gonadectomy of male mice, failed to result in the display of an E neuroprotectant response when tested as adults. Prepubertal gonadectomy of female mice, with or without testosterone treatment, abolished the capacity for E to produce neuroprotection against MA-induced NSDA neurotoxicity. Nor did prepubertal gonadectomy enable male mice to show an E neuroprotectant response. Taken together these results demonstrate that none of the manipulations performed within male mice enabled them to show an E-dependent neuroprotective response against MA-induced neurotoxicity of the NSDA system when tested as adults. For the female, it appears that the presences of gonadal steroids at these two developmental periods are needed for the display of an E-dependent neuroprotectant response within the adult.

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Dopamine / metabolism
  • Estrogens / metabolism
  • Estrogens / pharmacology*
  • Female
  • Gonads / growth & development
  • Gonads / metabolism
  • Male
  • Methamphetamine / antagonists & inhibitors
  • Methamphetamine / toxicity
  • Mice
  • Neostriatum / drug effects*
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Orchiectomy
  • Ovariectomy
  • Sex Characteristics*
  • Sexual Maturation / physiology
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / physiopathology
  • Testosterone / metabolism
  • Testosterone / pharmacology*


  • Estrogens
  • Neuroprotective Agents
  • Testosterone
  • Methamphetamine
  • Dopamine