Functional aspects of estrogen neuroprotection

V. BISAGNO; R. E. BOWMAN; V. N. LUINE

ENDOCRINE

Humana Press

Lugar: New Jersey; Año: 2003 p. 33 - 41

0969-711X

Evidence that estrogen protects neurons against toxic/ischemic insults or degenerative/aging processes is evident in a variety of in vitro and in vivo systems.  However, a critical remaining question is whether the demonstrated morphological and neurochemical protection by estrogen leads to a preservation of brain function or an enhanced ability to recover.  To date, little basic research is available on this issue.  Cognition is a critical function that might provide a sensitive way to examine this question.  As a first step, we present results showing that two chronic environmental insults, psychoactive drugs and stress, produce gender specific responses in cognitive abilities.  Specifically, females appear less sensitive than males to cognitive impairments following chronic exposure to these factors.  Results are presented in male and female rats utilizing cognitive tests that assess visual (object recognition) and spatial memory (object placement and radial arm maze) following chronic amphetamine, methamphetamine or daily restraint stress.  Following regimes of chronic stress or amphetamine, males were impaired on these tasks while females were either unaffected, less affected or enhanced in performance.  These observations suggest that differences in circulating gonadal hormone-levels between the sexes may contribute to the differential sensitivity of the sexes and provide endogenous neuroprotection for females. Suprisingly, ovariectomized females were still not impaired following a stress regimen that impaired males (21 days of daily restraint). Taken together with neurochemical data on estrogen neuroprotective effects, it is possible that neuroprotection by estrogen may result from hormone action during both sexual differentiation (organizational effect) and in adulthood (activational effect). These considerations and possible unwanted/untoward effects of chronic estrogen use are discussed in relation to the use of SERMs (selectective estrogen receptor modulators) for chronic treatment of both males and females.  In conclusion, while compelling evidence for neuroprotection by estrogen has been presented in anatomical and neurochemical studies, it is clear that the functional/behavioral aspects need further investigation.