# Microglial Expression of Serotonin Receptors Reveals Parallel Regulation of 5-HT2b and BDNF in the Rat Hippocampus

## TL;DR

The study shows that microglial serotonin receptors and BDNF levels are linked in the rat hippocampus, suggesting a role in mood regulation and neuroinflammation.

## Contribution

The paper reveals a parallel regulation of 5-HT2b and BDNF in microglia under serotonin deficiency.

## Key findings

- Microglial 5-HTR expression is transient and region-specific in the hippocampus and prefrontal cortex.
- 5-HT2b and BDNF are upregulated in the hippocampus of Tph2−/− rats lacking brain serotonin.
- Different 5-HTR subtypes play distinct roles in early network formation and response to serotonin changes.

## Abstract

What are the main findings?
Transient, region-specific microglial 5-HTR expression;Upregulated microglial 5-HT2b in Tph2−/− rats parallels BDNF levels.

Transient, region-specific microglial 5-HTR expression;

Upregulated microglial 5-HT2b in Tph2−/− rats parallels BDNF levels.

What are the implications of the main findings?
Temporal differences in 5-HTR signaling may drive adaptive responses to serotonin deficiency, with BDNF compensating at the later stage;Interplay between microglial serotonin and BDNF highlights potential targets for interventions in neuroinflammation.

Temporal differences in 5-HTR signaling may drive adaptive responses to serotonin deficiency, with BDNF compensating at the later stage;

Interplay between microglial serotonin and BDNF highlights potential targets for interventions in neuroinflammation.

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and region-specific gene expression of 5-HTRs on sorted microglia, paralleling changes in BDNF signaling, especially with 5-HT2b. Notably, both 5-HT2b and BDNF expression in the hippocampus was significantly upregulated in the absence of brain serotonin. Our data indicate distinct roles of 5-HTR subtypes in early network formation (5-HT1b, 5-HT5b) and in the response to endogenous changes (5-HT2b, 5-HT5a). Understanding serotonin–microglia interplay could offer therapeutic insights into the maintenance of mood via brain–immune cell interactions.