MHC class II in dopaminergic neurons prunes GABAergic synapses in neurodevelopmental disorders
- 1Saitama Medical University
Abstract
Although the brain was traditionally considered immune-privileged, recent studies show immune factors play key roles in brain function. Dysfunction of these factors is linked to neurodevelopmental disorders, but mechanisms remain unclear. Using a maternal immune activation (MIA) mouse model, we investigated immune-related genes in neurodevelopmental disorder pathogenesis. MIA mice showed increased locomotor activity and disrupted prepulse inhibition. RNA-seq and qPCR analyses revealed persistent increases in major histocompatibility complex class II (MHCII) expression and persistent decreases in GABAergic synapse-related gene expression, particularly glutamate decarboxylase (Gad) expression, in dopaminergic regions. These expressions were negatively correlated, and immunohistochemistry showed MHCII at postsynaptic GABAergic synapses on dopaminergic neurons. Patch-clamp recordings confirmed reduced mIPSC frequency in MIA mice. MHCII knockout mice showed opposite phenotypes, while MHCII overexpression in dopaminergic neurons decreased Gad expression. These results suggest MIA-induced MHCII upregulation enhances pruning of GABAergic synapses on dopaminergic neurons, leading to behavioral deficits.
Related
- Tunable neuronal microenvironments drive distinct functional phenotypes in human iPSCs-derived dopaminergic neurons
- Astrocytic GABAergic signaling in perioperative neurocognitive disorders: mechanisms and intervention strategies
- Coordinated orienting behavior emerges following unilateral optogenetic activation of Superior Colliculus GABAergic neurons
- A gαq signaling pathway in dopaminergic neurons suppresses memory
- Dopaminergic neurons linking threat processing to cardiac modulation and locomotor responses
BibTeX
@misc{murakami2026class,
title = {{MHC class II in dopaminergic neurons prunes GABAergic synapses in neurodevelopmental disorders}},
author = {G. Murakami and M. Hirasaki and M. Hashizume and A. Hirao and R. Ito and Y. Hojo and T. Nakano and N. Uozumi and T. Murakoshi},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747425},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747425v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - MHC class II in dopaminergic neurons prunes GABAergic synapses in neurodevelopmental disorders
AU - G. Murakami
AU - M. Hirasaki
AU - M. Hashizume
AU - A. Hirao
AU - R. Ito
AU - Y. Hojo
AU - T. Nakano
AU - N. Uozumi
AU - T. Murakoshi
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747425
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747425v1
AB - Although the brain was traditionally considered immune-privileged, recent studies show immune factors play key roles in brain function. Dysfunction of these factors is linked to neurodevelopmental disorders, but mechanisms remain unclear. Using a maternal immune activation (MIA) mouse model, we investigated immune-related genes in neurodevelopmental disorder pathogenesis. MIA mice showed increased locomotor activity and disrupted prepulse inhibition. RNA-seq and qPCR analyses revealed persistent increases in major histocompatibility complex class II (MHCII) expression and persistent decreases in GABAergic synapse-related gene expression, particularly glutamate decarboxylase (Gad) expression, in dopaminergic regions. These expressions were negatively correlated, and immunohistochemistry showed MHCII at postsynaptic GABAergic synapses on dopaminergic neurons. Patch-clamp recordings confirmed reduced mIPSC frequency in MIA mice. MHCII knockout mice showed opposite phenotypes, while MHCII overexpression in dopaminergic neurons decreased Gad expression. These results suggest MIA-induced MHCII upregulation enhances pruning of GABAergic synapses on dopaminergic neurons, leading to behavioral deficits.
ER -