Table 1.
Summary of animal studies comparing young and aged differences in cognitive function following stress. Various models of stress and immune system activation examined in young and aged animals show that aged animals have an exaggerated neuroinflammatory response and prolonged behavioral deficits compared to young animals. (↑ = “elevated,” ↓ = “reduced”)
| Stressor | Study | Animals | Age(s) | Sex | Model | Notable Findings |
|---|---|---|---|---|---|---|
| Peripheral infection | [101] | BALB/c mice | Young 3–6 m Aged 20–24 m |
Male | Lipopolysaccharide (LPS) i.p. injection | Exaggerated ↑ IL-1β, IL-6, lipid peroxidation in aged brain ↓ social behavior, food intake, weight loss in aged |
| [104] | F344XBN rats | Young 3 m Aged 24 m |
Male | Live E. coli i.p. injection | At baseline: ↑ hippocampal HMGB1 protein, mRNA in aged; ↑ HMGB1 protein in cerebrospinal fluid (CSF) of aged Following i.p. E. coli injection: Prolonged ↑ expression of IL-1β, IL-18, TNF in aged; prolonged sucrose anhedonia (depression) and ↓ juvenile social exploration in aged Inhibition of HMGB1: abrogated primed phenotype of aged brain to peripheral E. coli injection, restoring behavior to that of young animals |
|
| Central innate immune activation | [105] | BALB/c mice | Young 3–4 m Aged 20–22 m |
Male | LPS i.c.v. injection | Prolonged ↓ locomotor activity, social behavior, and food intake in aged ↑ cerebellar and hippocampal IL-1β, IL-6, and TNF expression in aged |
| Surgery | [106] | BALB/c mice | Young 4–6 m Aged 23–25 m |
Male | 1.5 cm abdominal incision and gentle manipulation of internal organs for 1 min | Anesthetic and analgesics: no effect on hippocampal IL-1β, IL-6 and TNF mRNA expression Surgery: ↑ IL-1β expression in aged hippocampus; locomotor activity unchanged in in young or aged mice |
| [107] | C57Bl6/J mice | 4 m | Female | 0.5 cm abdominal incision | Surgery ↑ anxiety, ↓ special memory | |
| [108] | C57Bl6/J mice | 2 m–8 m | Female | Simple laparotomy | Surgery ↑ total alpha-synuclein and S100β in the cortex, ↓ attention | |
| Stress | [109] | BALB/c mice | Young 3–5 m Aged 22–24 m |
Male | 30 min restraint stress daily for 4 days | Stress ↑ weight loss, exaggerated ↑ hippocampal and hypothalamic IL-1β mRNA expression in aged; exaggerated ↑ corticosterone in aged Higher hippocampal MHCII mRNA and immunohistochemistry staining in aged mice at baseline, and increased in aged mice following stress |