Tight Regulation of Major Histocompatibility Complex I for the Spatial and Temporal Expression in the Hippocampal Neurons

Abstract

The expression and function of immune molecules, such as major histocompatibility complex (MHC), within the developing and adult brain have been discovered over the past few years. Studies utilizing classical class I MHC knockout animals suggest that these molecules, in fact, play essential roles in the establishment, function, and modification of synapses in the CNS. Altered neuronal expression of class I MHC, as has been reported in pathological conditions, leads to aberrations in neuronal development and repair. In the hippocampus, cellular and molecular mechanisms that regulate synaptic plasticity have heretofore been extensively studied. It is for this reason that multiple studies directed at better understanding the expression, regulation, and function of class I MHC within the hippocampus have been undertaken. Since several previous reviews have addressed the roles of class I MHC in the formation and function of hippocampal connections, the present review will focus on describing the spatial and temporal expression of class I MHC in developing, healthy adult, and aging hippocampus. Herein, we also review current literatures exploring mechanisms that regulate class I MHC expression in murine hippocampus. With this review, we aim to facilitate a deeper mechanistic understanding into the complex tight regulation of MHC I expression in hippocampus, which are needed as we explore the potential for targeting MHC I for therapeutic intervention in normal aging and in neurodegenerative diseases in the future.

Local patterns of genetic sharing challenge the boundaries between neuropsychiatric and insulin resistance-related conditions

“…We cannot provide a clear explanation of this finding, but it may lie in the intricate balance of pro-inflammatory and anti-inflammatory factors in immune response, in which MHC genes play a critical role (Tamouza et al, 2021). The differential expression of genes in the MHC region across different tissues and lifespan could also contribute to this observation (Shen and Zhang, 2021). Experimental validation of these findings will therefore be necessary to determine the exact functional implication of the observed genetic associations.…”

Comprehensive analysis of genetic risk loci uncovers novel candidate genes and pathways in the comorbidity between depression and Alzheimer’s disease

“…This process tightly regulates synaptic signaling under control of components of the immune system [ 70 ]. For example, cytokines produced by immune cells affect the potentiation of neurons and neuronal activity in the hippocampus [ 71 , 72 ] and synaptic MHC class I proteins can influence neuronal potentiation and synaptic density [ 57 , 73 , 74 ]. Although a link for the immune system in the etiologies of depression and AD is known (reviewed in [ 75 ]), this is not yet the case for synaptoimmunology.…”

HLA‐A23/HLA‐A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasma

“…Despite the body of knowledge from animal and human studies, the exact role played by MHC class I molecules in modulating biological processes of the CNS and their involvement in neurological disorders is a matter of intensive investigations. 17 Importantly, in the mice studies both cell surface and soluble forms of H-2 class I molecules were implicated in synaptic plasticity and neurogenesis, likely through cis-trans-interactions with surface receptors important for brain function. [18][19][20] In this respect, studies characterizing the levels of soluble HLA class I have primarily focused on the non-classical molecules HLA-G and HLA-E in autoimmunity, cancer, infection, diabetes, and transplantation.…”