Hippocampal neuroinflammation induced by lipopolysaccharide causes sex-specific disruptions in action selection, food approach memories, and neuronal activation

Kiruthika Ganesan; Sahar Ghorbanpour; William Kendall; Sarah Thomas Broome; Joanne M Gladding; Amolika Dhungana; Arvie Rodriguez Abiero; Maedeh Mahmoudi; Alessandro Castorina; Michael D Kendig; Serena Becchi; Veronika Valova; Louise Cole; Laura A Bradfield

doi:10.1016/j.bbi.2024.11.011

Hippocampal neuroinflammation induced by lipopolysaccharide causes sex-specific disruptions in action selection, food approach memories, and neuronal activation

Brain Behav Immun. 2024 Nov 14:124:9-27. doi: 10.1016/j.bbi.2024.11.011. Online ahead of print.

Affiliations

¹ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Centre for Neuroscience and Regenerative Medicine, St. Vincent's Centre for Applied Medical Research, St. Vincent's Health Network, Sydney, New South Wales 2010, Australia; School of Psychology, Faculty of Science, University of Sydney, New South Wales 2006, Australia.
² School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Institute of Cell and Tissue Culture Technologies, Department of Biotechnology, BOKU University, Vienna, Austria.
³ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
⁴ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
⁵ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Centre for Neuroscience and Regenerative Medicine, St. Vincent's Centre for Applied Medical Research, St. Vincent's Health Network, Sydney, New South Wales 2010, Australia.
⁶ Decision Neuroscience Laboratory, School of Psychology, University of New South Wales Sydney, Sydney, New South Wales 2052, Australia; Teva Pharmaceuticals, Sydney, New South Wales 2113, Australia.
⁷ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, New South Wales 2050, Australia.
⁸ School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Centre for Neuroscience and Regenerative Medicine, St. Vincent's Centre for Applied Medical Research, St. Vincent's Health Network, Sydney, New South Wales 2010, Australia. Electronic address: [email protected].

PMID: 39547520
DOI: 10.1016/j.bbi.2024.11.011

Abstract

Hippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt this behaviour is unknown. We investigated this question here using mice. First, the application of an endotoxin to primary cultures containing only hippocampal neurons did not affect their activation. However, when the same endotoxin was applied to mixed neuronal/glial cultures it did increase neuronal activation, providing initial indications of how it might be able to effect behavioural change. We next showed neuroinflammatory effects on behaviour directly, demonstrating that intra-hippocampal administration of the same endotoxin increased locomotor activity and accelerated goal-directed learning in both male and female mice. In contrast, lipopolysaccharide-induced hippocampal neuroinflammation caused sex-specific disruptions to the acquisition of instrumental actions and to Pavlovian food-approach memories. Finally, we showed that LPS-induced hippocampal neuroinflammation had a sexually dimorphic effect on neuronal activation: increasing it in females and decreasing it in males.

Keywords: Astrocytes; Goal-directed action; Hippocampus; Instrumental action selection; Locomotor activity; Microglia; Neuroinflammation; Pavlovian memory; Sex differences.