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Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions.
Porcher, Latarsha; Bruckmeier, Sophie; Burbano, Steven D; Finnell, Julie E; Gorny, Nicole; Klett, Jennifer; Wood, Susan K; Kelly, Michy P.
Affiliation
  • Porcher L; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA.
  • Bruckmeier S; Department of Anatomy & Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSFII Rm 216, Baltimore, MD, 21201, USA.
  • Burbano SD; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA.
  • Finnell JE; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA.
  • Gorny N; Department of Anatomy & Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSFII Rm 216, Baltimore, MD, 21201, USA.
  • Klett J; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA.
  • Wood SK; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA.
  • Kelly MP; Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC, 29209, USA. Michy.Kelly@som.umaryland.edu.
J Neuroinflammation ; 18(1): 219, 2021 Sep 22.
Article in En | MEDLINE | ID: mdl-34551810
ABSTRACT

BACKGROUND:

Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound-particularly for interleukin 6 (IL-6)-possibly due to differences in sex, species/strain, and/or the brain regions studied.

METHODS:

As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate.

RESULTS:

In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1ß, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1ß in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1ß. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments.

CONCLUSIONS:

Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Cytokines / Sex Characteristics / Hippocampus Limits: Animals Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Cytokines / Sex Characteristics / Hippocampus Limits: Animals Language: En Journal: J Neuroinflammation Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: United States