Diminished levels of the chemokine fractalkine in post-mortem prefrontal cortex in schizophrenia but not bipolar disorder

Abstract

Objectives

Though the pathophysiology underlying schizophrenia (SCZ) and bipolar disorder (BD) is not fully understood, immune function may be dysregulated, with microglia, the brain’s resident immune cells, implicated in this process. Signalling between the neuronal chemokine fractalkine (CX3CL1) and its microglial receptor CX3CR1 facilitates neuron-microglia interactions, influencing microglial activation and synaptic function. As such, alterations in fractalkine signalling may contribute to immune and synaptic alterations observed in SCZ and BD.

Methods

Protein and mRNA expression of fractalkine, CX3CR1, and a disintegrin and metalloproteinase 10 (ADAM10), a sheddase that cleaves fractalkine, were quantified in post-mortem frontal cortex from individuals with SCZ (n = 35), BD (n = 34), and matched controls (n = 35) using immunoblotting and droplet digital PCR. In addition, the relationship between fractalkine pathway members and levels of the pre-synaptic protein SNAP-25 was examined.

Results

Fractalkine protein levels were significantly lower in SCZ relative to controls. Expression of members of the fractalkine signalling pathway was unchanged in BD. CX3CR1 protein levels were significantly correlated with SNAP-25 levels.

Conclusions

The observed deficit in fractalkine protein levels in SCZ is consistent with impaired neuron-microglia crosstalk in this disorder. Furthermore, our data are suggestive of an aberrant association between microglial function and synaptic density in SCZ.

Keywords:

• Immunology
• post-mortem brain
• microglia
• synapse

Acknowledgements

Post-mortem brain tissue was donated by the Stanley Medical Research Institute’s brain collection. The authors thank Dr. W.G. Honer for generously providing the SNAP-25 antibody. A. Ypsilanti performed quantification of SNAP-25.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a NARSAD Independent Investigator Grant from the Brain and Behaviour Research Foundation [grant number 25711]. CLB received salary awards from the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. The funding sources had no role in study design, collection, analysis and interpretation of data or the writing of the manuscript.