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Advanced Neurologyurology
Advanced Ne TRPM2 in neurological disorders

to elucidate the pathophysiology of neurological disease, 2. Expression, distribution, and function of
may not recapitulate the complexity of human diseases. the TRPM2 ion channel
This has been an issue in clinical translation of AD mouse
model findings where strategies to remove plaques in mice Real-time quantitative reverse transcription polymerase
do not cure AD in humans . In some cases, therapeutic chain reaction reveals TRPM2 expression in all peripheral
[5]
[17]
treatments for ischemia, such as administering growth regions analyzed aside from cartilage and bone . This
factors, have had side effects such as blood–brain barrier includes expression in bone marrow, lung, spleen, heart,
(BBB) leakage . and pancreas, with highest relative expression levels
[6]
apparent in the brain . Within the central nervous
[17]
The transient receptor potential melastatin 2 (TRPM2) system (CNS), TRPM2 is among the most abundant of all
ion channel is an important member of the calcium- the TRPM channels . Regarding regional distribution
[17]
permeable, non-selective, cation conducting TRP family. patterns within the human CNS, a major 6.2 kb trpm2
It is sensitive to perturbations in the cellular environment transcript was demonstrated by northern blotting in various
and is essential to both cell survival and the induction of regions, including the cerebral cortex, hippocampus,
cell death. TRPM2 is located at the plasma membrane thalamus, cerebellum, and substantia nigra, while a minor
and/or lysosomal compartments, with a broad tissue 5.5 kb transcript was detected only in the striatum [18,19] .
distribution profile indicative of its involvement in multiple Trpm2 mRNA and TRMP2 protein are also detected in
physiological processes [7,8] . corresponding brain regions in murine models [18,20,21] .
TRPM2 is highly expressed in a variety of cells in the The Allen Mouse Brain Atlas has been an instrumental
brain and is, therefore, an attractive target for improving tool in mapping Trpm2 gene expression within a three-
brain function. Modulation of TRPM2 has the potential dimensional reference framework [13-15] . The available high-
to prevent apoptosis, minimize BBB leakage, and reduce resolution in situ hybridization (ISH) map of Trpm2 expression
the inflammatory response. Activated in response to in a male postnatal day 56 mouse, corresponding to the
oxidative stress and reactive oxygen species (ROS), which adult stage, provides a transcriptomic profile of the channel.
are common among different diseases, TRPM2 is involved Representative images of Trpm2 expression in a sagittal section
in many neurological disorders, such as Parkinson’s disease and three-dimensional reconstruction of the mouse brain are
(PD), AD, ischemia, brain tumors, and aging [9,10] . TRPM2 shown in Figure 1A and 1B, respectively, with the background
is also implicated in the evolution and development of signal subtracted and the relative expression level displayed in
neuropsychiatric disorders. Our own studies in neonatal cool colors (low expression) to hot colors (high expression).
hypoxic-ischemic-induced mice demonstrate reduced Quantification of this dataset demonstrates that at this
infarction volume and glial cell activation in response to developmental stage, the level of Trpm2 mRNA is greatest in
TRPM2 gene knockout or administration of a TRPM2 the thalamus followed by the medulla, midbrain, and cortical
inhibitor [11,12] . This suggests that TRPM2 inhibition confers subplate (Figure 1C) [13-15] . It is important to note that the ISH
neuroprotective effects in neurological diseases that share data are semi-quantitative because of the signal amplification
common underlying molecular mechanisms. process, but nevertheless it enables the visualization of Trpm2
This review begins with an introduction describing mRNA localization coupled with intensity, which helps to
the expression, distribution, and function of the guide the study of neurological processes in which TRPM2
TRPM2 channel. We use data from the Allen Mouse is implicated. For example, Trpm2 is expressed in the preoptic
Brain Atlas [13-15] to highlight TRPM2 expression across area of the hypothalamus, with its function confirmed by
the brain and discuss the common mechanisms by which electrophysiological recordings. Cultured preoptic neurons
-/-
TRPM2 activation induces neural dysfunction or injury. In from TRPM2-deficient (Trpm2 ) mice had reduced responses
a previous review , we focused on the role of the TRPM2 to high temperatures above 37°C, compared with wild-type
[16]
channel in ischemia/hypoxia. Here, we discuss TRPM2 in a cultures, indicating that TRPM2 serves as a hypothalamic
[22,23]
number of neurological conditions or disorders, including heat sensor . TRPM2 is also involved in hippocampal
PD, AD, ischemia, TBI, and psychiatric disorders, synaptic plasticity and long-term depression (LTD), with
[24]
highlighting the common mechanisms and pathways hippocampal TRPM2 ablation conferring impaired LTD .
between the conditions. We primarily focus on the use of Similarly, knowledge of TRPM2 regional localization paired
animal (rodent) disease models as well as in vitro studies with an understanding of its modulation and signaling
to better understand the role that TRPM2 activation plays patterns implicates this channel in a variety of neurological
in mediating brain dysfunction or injury. The review disorders.
concludes by summarizing the current status of TRPM2 TRPM2 has been detected in various cell types,
research and potential future developments in the field. including neurons and glial cells of the CNS, other

Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/an.v1i1.3