mRNA expression of transient receptor potential melastatin (TRPM) channels 2 and 7 in perinatal brain development

Abstract

TRPM7 and TRPM2 are non-specific cation channels of the Transient Receptor Potential channel superfamily. Each channel has gained attention for their potential to mediate oxidative and anoxic cell death (Rama and García, 2016; Nazıroğlu, 2011a; Abiria et al., 2017; Sun, 2017), however their physiological expression and roles in the developing brain remain poorly defined. We employed real-time reverse transcription PCR to examine mRNA expression of TRPM7 and TRPM2 in the developing rat brain and brain-specific cell types. We determined the temporal and spatial expression patterns at four developmental time points (postnatal day 7, 14, 21, and 90) in four critical regions of the brain (cortex, hippocampus, striatum, and cerebellum) and examined gene expression in neuronal, astrocytic, and microglial primary cell cultures. Our results revealed that TRPM7 mRNA expression peaks in the cortex at 2-weeks after birth, and thus correlates most closely with a period of rat brain development associated with neurite outgrowth, which is heightened at 2-weeks after birth. Our cell-specific gene expression assays revealed that TRPM7 was expressed at equivalent levels in neurons, astrocytes, and microglia. Conversely, TRPM2 was most highly expressed in microglia with little expression in neurons and astrocytes. In the hippocampus and striatum, the expression profile of TRPM2 parallels the perinatal expression timeline for microglial infiltration and maturation in the rat brain. Microglial maturation is highest from the time of birth, up to 7-days, but subsequently declines. The latter developmental expression profiles indicate a role for TRPM2 in microglial activation.

Functional Restoration following Global Cerebral Ischemia in Juvenile Mice following Inhibition of Transient Receptor Potential M2 (TRPM2) Ion Channels

“…In addition, TRPM2 channels can be acutely inhibited at delayed time points after CA/CPR by applying tatM2NX onto acute hippocampal slices which reverses LTP deficits in adults, indicating that TRPM2 channels impair synaptic plasticity through persistent activation [ 10 ]. Together, our data highlight two important hypotheses: (a) although TRPM2 channels are expressed at similar levels in juvenile and adults ( Figure 1 and see [ 39 ]), the role of this channel in cell death is age dependent, and (b) TRPM2 channel activation impairs synaptic plasticity both acutely and chronically and may be targeted to restore cognitive function after global cerebral ischemia, despite a lack of neuroprotection in the young brain. We suggest that disparate pathways exist for cell death and synaptic impairment by TRPM2.…”

Pharmacological Modulation of TRPM2 Channels via TRPM2 Pathway Leads to Neuroprotection in MPTP-induced Parkinson’s Disease in Sprague Dawley Rats

“…It has been shown that the TRPM2 is widely expressed in the human and as well as rat striatum [53,54]. From our ndings, it is now established that both inhibitors exhibit the neuroprotective effects in the MPTP-induced PD animals.…”

One Single Nucleotide Polymorphism of the TRPM2 Channel Gene Identified as a Risk Factor in Bipolar Disorder Associates With Autism Spectrum Disorder in a Japanese Population

“…TRPM2 resides not only in neurons, but also astrocytes or microglial cells, which play a role in cognitive functions [91][92][93][94]. The mRNA expression profile in microglia of TRPM2 in the hypothalamus and striatum of the developing rat brain has been shown to be paralleled with the perinatal expression timeline for microglial infiltration and maturation [95]. TRPM2 has been shown to be involved in embryonic neurogenesis [96].…”