Sexually differentiated microglia and CA1 hippocampal synaptic connectivity.
Tim M PrengelBianka BrunneMoataz HabiballaGabriele M RunePublished in: Journal of neuroendocrinology (2023)
Microglia have been shown to sculpt postnatal circuitry from birth up to adulthood due to their role in both synapse formation, synaptic pruning, and the elimination of weak, redundant synapses. Microglia are differentiated in a sex-dependent manner. In this study, we tested whether sexual differentiation of microglia results in sex-dependent postnatal reorganization of CA1 synaptic connectivity in the hippocampus. The stereological counting of synapses in mice using electron microscopy showed a continuous rise in synapse density until the fourth week, followed by a plateau phase and loss of synapses from the eighth week onwards, with no difference between sexes. This course of alteration in synapse numbers did not differ between sexes. However, selectively, on postnatal day (P) 14 the density of synapses was significantly higher in the female than in the male hippocampus. Higher synapse density in females was paralleled by higher activity of microglia, as indicated by morphological changes, CD68 expression, and proximity of microglia to synaptic sites. In Thy1-GFP mice, consistent with increased synapse numbers, bouton density was also clearly increased in females at P14. At this time point, CD47 expression, the "don't eat me" signal of neurons, was similar in males and females. The decrease in bouton density thereafter in conjunction with increased synapse numbers argues for a role of microglia in the formation of multispine boutons (MSB). Our data in females at P14 support the regulatory role of microglia in synapse density. Sexual differentiation of microglia, however, does not substantially affect long-term synaptic reorganization in the hippocampus.
Keyphrases
- inflammatory response
- neuropathic pain
- prefrontal cortex
- preterm infants
- poor prognosis
- spinal cord
- mental health
- spinal cord injury
- type diabetes
- depressive symptoms
- metabolic syndrome
- machine learning
- functional connectivity
- blood brain barrier
- skeletal muscle
- randomized controlled trial
- electronic health record
- high fat diet induced
- deep learning
- long non coding rna
- resting state
- placebo controlled
- double blind
- data analysis