Maternal immune activation increases the corticosterone response to acute stress without affecting the hypothalamic monoamine content and sleep patterns in male mice offspring

Background/Aims: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. Methods: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. Results and Conclusion: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring.

Curcumin requires tumor necrosis Factor α signaling to alleviate cognitive impairment elicited by Lipopolysaccharide

A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2) signaling. In vivo, the ability of curcumin to counteract hippocampusdependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl- D –aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.