title: Estrogen-induced neuroprotective and anti-inflammatory effects are dependent on the brain areas of middle-aged female rats.
abstract: 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.
  
  
  
  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.
  
  
  
  Ovariectomized early MA female Sprague-Dawley rats (n=8/group) were implanted with 17β-estradiol (E2) 30-day release pellets (0.6μg and 300μg). 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Uday P
authors.initials: UP
authors.lastname: Pratap
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Anushree
authors.initials: A
authors.lastname: Patil
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Himanshu R
authors.initials: HR
authors.lastname: Sharma
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Lalgi
authors.initials: L
authors.lastname: Hima
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Chockalingam
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Hariharan
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Sushrut
authors.initials: S
authors.lastname: Shitoot
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Priyanka
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India. Electronic address: thyagarajan.s@ktr.srmuniv.ac.in.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: ThyagaRajan
mesh_terms: D000375:Aging; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects*; D002802:Cholinesterases / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020932:Nerve Growth Factor / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D004958:Estradiol; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D011770:Pyruvate Kinase; D002802:Cholinesterases; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Akt; CREB; Cholinesterase; ERK; Nerve growth factor; Tyrosine hydroxylase