Loss of PPARα perpetuates sex differences in stroke reflected by peripheral immune mechanisms

Abby L. Dotson, Jianming Wang, Jian Liang, Ha Nguyen, Dustin Manning, Julie Saugstad, Halina Offner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that plays a role in immune regulation. Because of its expression in cerebral tissue and immune cells, PPARα has been examined as an important regulator in immune-based neurological diseases. Many studies have indicated that pre-treatment of animals with PPARα agonists induces protection against stroke. However, our previous reports indicate that protection is only in males, not females, and can be attributed to different PPARα expression between the sexes. In the current study, we examine how loss of PPARα affects male and female mice in experimental stroke. Male and female PPARα knockout mice were subject to middle cerebral artery occlusion (MCAO) or sham surgery, and the ischemic (local) or spleen specific (peripheral) immune response was examined 96 h after reperfusion. We found that loss of PPARα perpetuated sex differences in stroke, and this was driven by the peripheral, not local, immune response. Specifically we observed an increase in peripheral pro-inflammatory and adhesion molecule gene expression in PPARα KO males after MCAO compared to females. Our data supports previous evidence that PPARα plays an important role in sex differences in the immune response to disease, including stroke.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalMetabolic Brain Disease
DOIs
StateAccepted/In press - Feb 12 2016

Fingerprint

PPAR alpha
Sex Characteristics
Stroke
Middle Cerebral Artery Infarction
Cytoplasmic and Nuclear Receptors
Gene expression
Knockout Mice
Surgery
Reperfusion
Animals
Transcription Factors
Adhesion
Spleen
Tissue
Gene Expression
Molecules

Keywords

  • Experimental stroke
  • Inflammation
  • Knock out
  • PPARα
  • Sex difference

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Loss of PPARα perpetuates sex differences in stroke reflected by peripheral immune mechanisms. / Dotson, Abby L.; Wang, Jianming; Liang, Jian; Nguyen, Ha; Manning, Dustin; Saugstad, Julie; Offner, Halina.

In: Metabolic Brain Disease, 12.02.2016, p. 1-10.

Research output: Contribution to journalArticle

Dotson, Abby L. ; Wang, Jianming ; Liang, Jian ; Nguyen, Ha ; Manning, Dustin ; Saugstad, Julie ; Offner, Halina. / Loss of PPARα perpetuates sex differences in stroke reflected by peripheral immune mechanisms. In: Metabolic Brain Disease. 2016 ; pp. 1-10.
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