Chronic g-CSF increases the neutrophil-lymphocyte ratio and decreases plasma corticosterone concentrations in Peromyscus maniculatus without impacting compulsive-like stereotypy

Abstract

Increasing evidence points to brain-immune mechanisms underlying conditions characterized by neurocognitive rigidity. However, causal evidence remains elusive. Thus, the present work first aimed to investigate the naturalistic associations between rigid motor stereotypy and non-specific markers of systemic inflammation, i.e., the neutrophil-lymphocyte ratio (NLR) and plasma corticosterone concentrations in deer mice. We then explored causal immune-brain interactions by bolstering the NLR, using the recombinant human granulocyte colony-stimulating factor (g-CSF), i.e., pegfilgrastim (Peg). One-hundred and twenty (120) 3-week-old deer mice (both sexes) were exposed to nine weekly injections with normal water for injection or Peg (n = 60 per group) and then assessed for stereotypical expression. Stereotypical behaviour, the NLR, and plasma corticosterone were then measured. Our findings show that 1) NLR and plasma corticosterone concentrations do not predict stereotypical expression and 2) chronic Peg exposure significantly increased the NLR and decreased the plasma corticosterone concentration in mice of both sexes, without impacting stereotypical expression. While valuable findings related to the relationship between exogenous NLR manipulation and immune system functioning were highlighted, continued investigation will be necessary to further explore whether spontaneous stereotypy in deer mice may be associated with immune-inflammatory involvement.