A Novel Localization of METTL7A in Bergmann Glial Cells in Human Cerebellum

Int J Mol Sci. 2023 May 7;24(9):8405. doi: 10.3390/ijms24098405.

Abstract

Methyltransferase-like protein 7A (METTL7A) is a member of the METTL family of methyltransferases.Little information is available regarding the cellular expression of METTL7A in the brain. METTL7A is commonly located in the endoplasmic reticulum and to a lesser extent, in the lipid droplets of some cells. Several studies have reported altered protein and RNA levels in different brain areas in schizophrenia. One of these studies found reduced protein levels of METTL7A in the cerebellar cortex in schizophrenia and stress murine models. Since there is limited information in the literature about METTL7A, we characterized its cellular and subcellular localizations in the human cerebellum using immunohistochemical analysis with laser confocal microscopy. Our study reveals a novel METTL7A localization in GFAP-positive cells, with higher expression in the end-feet of the Bergmann glia, which participate in the cerebrospinal fluid-brain parenchyma barrier. Further 3D reconstruction image analysis showed that METTL7A was expressed in the contacts between the Bergmann glia and Purkinje neurons. METTL7A was also detected in lipid droplets in some cells in the white matter. The localization of METTL7A in the human cerebellar glia limitans could suggest a putative role in maintaining the cerebellar parenchyma homeostasis and in the regulation of internal cerebellar circuits by modulating the synaptic activity of Purkinje neurons.

Keywords: Bergmann glia; METTL7A; cerebrospinal fluid-brain barrier; glia limitans; postmortem cerebellum; schizophrenia.

MeSH terms

  • Animals
  • Cerebellar Cortex
  • Cerebellum* / metabolism
  • Humans
  • Mice
  • Neuroglia* / metabolism
  • Neurons / metabolism
  • Purkinje Cells / metabolism

Substances

  • METTL7A protein, human