Estrogen-induced neuroprotective and anti-inflammatory effects are dependent on the brain areas of middle-aged female rats

Uday P. Pratap, Anushree Patil, Himanshu R. Sharma, Lalgi Hima, Ramanathan Chockalingam, Murali M. Hariharan, Sushrut Shitoot, Hannah P. Priyanka, Srinivasan ThyagaRajan

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Reproductive aging in females is characterized by fluctuations and precipitous decline in estrogen levels, which may lead to reduction in cognitive function and age-associated neurodegenerative disorders. The nature of estrogen-mediated neuronal plasticity is unknown during reproductive aging. We hypothesize that estrogen treatment of early middle-aged ovariectomized rats may exert specific effects in the brain by modulating signaling pathways regulating metabolic enzymes, inflammatory markers, antioxidant status, cholinergic function and survival signals. Purpose: To investigate the mechanisms of estrogen-induced effects on neuroprotection and neuroinflammation through the involvement of intracellular signaling pathways in brain areas of ovariectomized (OVX) middle-aged (MA) female rats. Methods: Ovariectomized early MA female Sprague-Dawley rats (n = 8/group) were implanted with 17β-estradiol (E2) 30-day release pellets (0.6 μg and 300 μg). At the end of the treatment period, frontal cortex (FC), striatum (STR), medial basal hypothalamus (MBH), and hippocampus (HP) were isolated and examined for the expression of tyrosine hydroxylase (p-TH), nerve growth factor (NGF), p-NF-κB (p50 and p65)and p-ERK, p-CREB, p-Akt, and activities of cholinesterases and antioxidant enzymes, key regulatory enzymes of metabolic pathways, and nitric oxide production. Results: E2 enhanced p-TH expression in FC and HP, reduced NGF expression in HP, and suppressed p-NF-κB expression in FC and STR. It also increased the expression of molecular markers (p-ERK, p-CREB and p-Akt), and nitric oxide production in various brain areas, while differentially regulating the activities of metabolic enzymes and cholinesterases. Conclusion: Estrogen modulates the neural and inflammatory factors, and intracellular markers depending on the brain areas that may influence differential remodeling of neuronal circuitry which can be used to develop therapeutic strategies in cognitive impairment and neurodegenerative disorders in aging.

Original languageEnglish (US)
Pages (from-to)238-253
Number of pages16
JournalBrain Research Bulletin
StatePublished - Jun 1 2016
Externally publishedYes


  • Akt
  • CREB
  • Cholinesterase
  • ERK
  • Nerve growth factor
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • General Neuroscience


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