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Turkish Journal of Medical Sciences

Abstract

Background/aim: Depression is a prevalent neuropsychiatric disorder with a complex etiology and a higher burden in women. The inflammation hypothesis, initially proposed based on parallels between depression and sickness behavior, has gained increasing support from accumulating evidence. EphA4, a regulator of synaptic plasticity, is highly expressed in the hippocampus and functions as a negative modulator of neuroplasticity.

Materials and methods: Hippocampal EphA4 expression was investigated in female Wistar rats subjected to lipopolysaccharide-induced acute systemic inflammation. Acute systemic inflammation was induced by intraperitoneal administration of lipopolysaccharide (5 mg/ kg). Depression-like behaviors were assessed using the open-field test and tail-suspension test, while systemic inflammation was evaluated using white blood cell counts and leukocyte differentials. Immunohistochemical analyses for Iba-1 and BDNF, immunofluorescence for EphA4, and TUNEL assays were performed on paraffin-embedded brain sections.

Results: Lipopolysaccharide exposure was found to elicit a microglial response in the hippocampus and to be associated with increased apoptosis. EphA4 expression tended to be higher across multiple hippocampal layers in the cornu ammonis and dentate gyrus, whereas BDNF levels appeared to be reduced in selected cornu ammonis subfields.

Conclusion: These findings suggest that acute systemic inflammation may be associated with depression-like behaviors, potentially through hippocampal neuroinflammation, altered neurotrophic signaling, and changes in EphA4 expression. EphA4 may therefore represent a circuit-level mediator of inflammation-related synaptic alterations and may be considered a potential target for future therapeutic strategies in inflammation-associated neuropathologies.

Author ORCID Identifier

SENEM YAVAŞ: 0000-0002-6949-1210

ÖZKAN YAVAŞ: 0000-0001-9811-9920

AYŞE AKBAŞ: 0000-0002-0091-9012

SEDA IŞIKLAR: 0000-0003-3922-2009

SEMİHA ERSOY: 0000-0002-6419-0304

DOI

10.55730/1300-0144.6405

Keywords

Depression, EphA4, hippocampus, lipopolysaccharide, neuroinflammation

First Page

1598

Last Page

1611

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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