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Advanced Neurology TRPM2 in neurological disorders

A B C

Figure 1. Allen Mouse Brain Atlas in situ hybridization and brain explorer database for TRPM2 gene expression. (A) Representative anatomical reference
atlas of the mouse at postnatal day (P) 56, in a sagittal section (left panel). Representative in situ hybridization image at the corresponding sagittal section
of the brain showing the relative location and intensity of Trpm2 mRNA (upper panel). Representative expression mask at the corresponding sagittal
section with background signal subtracted showing low expression in cool colors and high expression in warm colors (middle panel). Representative
TRPM2 protein structure comprising six transmembrane helices, labeled S1 – S6. The amino terminus contains a Ca -calmodulin (CaM)-binding
2+
motif that participates in channel activation. The carboxyl terminus contains a TRP domain (TRP), a coiled-coil domain, and a ~270 residue nucleoside
diphosphate-linked moiety X-type homology motif (NUDT9) that interacts with adenosine diphosphate ribose (lower panel). Allen Reference Atlas –
Mouse Brain, https://atlas.brain-map.org/and Allen Mouse Brain Atlas, https://mouse.brain-map.org/experiment/show/69288417. (B) Construction of
a three-dimensional image of the mouse brain at P56 displaying the in situ hybridization gene expression data of Trpm2. Trpm2 expression intensity
(sum of expression pixel intensity/sum of expression pixels) is first shown alone, then with a coronal section, and then with a coronal section and outer
structures. Low expression is indicated in cool colors of blue to green, while high expression in indicated in warm colors of yellow to red hues. Allen Mouse
Brain Atlas, 3D brain explorer. (C) Relative Trpm2 expression in specific analyzed brain structures. Allen Mouse Brain Atlas, https://mouse.brain-map.
org/experiment/show/69288417. TH: Thalamus; MY: Medulla; MB: Midbrain; CTXSP: Subcortical plate; P: Pons; PAL: Pallidum; OLF: Olfactory areas;
CB: Cerebellum; HPF: Hippocampal formation; HY: Hypothalamus; STR: Striatum. Figure generated with BioRender.

immune cells, and endothelial cells. As a Ca -permeable by TRPM2 being present in the cells of the peripheral
2+
channel activated by oxidative stress, TRPM2 has been immune system, including neutrophils, macrophages,
investigated in pathological conditions characterized monocytes, and lymphocytes [29-32] . Finally, TRPM2 has
by Ca -induced cytotoxicity and high levels of ROS been implicated in cerebrovascular integrity because
2+
and hydrogen peroxide (H O ). TRPM2 is abundant in of its expression in endothelial cells. ROS production
2
2
hippocampal pyramidal neurons, dopaminergic neurons stimulates excessive TRPM2-mediated Ca entry through
2+
of the substantia nigra, and cortical neurons [21,25,26] . In the endothelial plasmalemma, which, in turn, activates
[33]
glial cells, TRPM2-mediated Ca currents in response caspase-3-mediated apoptosis . Meanwhile, TRPM2
2+
to H O have been observed in cultured microglia inhibition prevents thrombin-induced BBB permeability
2
2
2+
heterogeneously expressing TRPM2 . TRPM2 at mRNA through the blockade of Ca influx in brain capillary
[27]
[34]
and protein levels has been detected in astrocytes, with endothelial cells . These results highlight the role of
siRNA transfection leading to a significant reduction in TRPM2 in modulating BBB integrity under physiological
[28]
astrocyte-mediated interleukin (IL)-6 release . These and pathological conditions.
studies indicate that TRPM2 is present in both microglial In regard to subcellular localization, TRPM2 is
cells and astrocytes, where it plays a key role in the primarily a plasma membrane channel. However,
inflammatory response and promotion of cytokine release immunofluorescence of TRPM2 in pancreatic β- cells has
under pathological conditions. This role is supported revealed intracellular localization, including in lysosomes.
Volume 1 Issue 1 (2022) 3 https://doi.org/10.36922/an.v1i1.3