Sexually differentiated microglia and CA1 hippocampal synaptic connectivity

TY - JOUR

T1 - Sexually differentiated microglia and CA1 hippocampal synaptic connectivity

AU - Prengel, Tim M

AU - Brunne, Bianka

AU - Habiballa, Moataz

AU - Rune, Gabriele M

N1 - © 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

KW - Mice

KW - Male

KW - Female

KW - Animals

KW - Microglia/metabolism

KW - Hippocampus

KW - Neurons

KW - Synapses/metabolism

KW - Presynaptic Terminals

U2 - 10.1111/jne.13276

DO - 10.1111/jne.13276

M3 - SCORING: Journal article

C2 - 37170708

VL - 35

SP - e13276

JO - J NEUROENDOCRINOL

JF - J NEUROENDOCRINOL

SN - 0953-8194

IS - 5

ER -