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Ischemia/reperfusion (I/R) injury is the main cause of tissue damage and dysfunction. I/R injury is characterized by Ca(2+) overload and production of reactive oxygen species (ROS), which play critical roles in the process of I/R injury to the brain, heart and kidney, but the underlying mechanisms are largely elusive. Recent evidence demonstrates that TRPM2, a Ca(2+)-permeable cationic channel and ROS sensor, is involved in I/R injury, but whether TRPM2 plays a protective or detrimental role in this process remains controversial. In this review, we discuss the recent progress in understanding the role of TRPM2 in reperfusion process after brain, heart and kidney ischemia and the potential of targeting TRPM2 for the development of therapeutic drugs to treat I/R injury.

Aim: N -methyl- D -aspartate receptors (NMDAR) are heteromeric complexes primarily assembled from NR1 and NR2 subunits. In normal conditions, NR2 sub-units assemble into homodimers in the endoplasmic reticulum (ER). These homodimers remain in the ER until they coassemble with NR1 dimers and are trafficked to the cell surface. However, it still remains unclear whether functional homomeric NMDAR exist in physiological or pathological conditions. Methods: We transfected GFP-NR2A alone into HEK293 cells, treated the cells with PKC activator 12-myristate-13 acetate (PMA), and then detected surface NR2A sub-units with a live cell immunostaining method. We also used a series of NR2A mutants with a partial deletion of its C-terminus to identify the regions that are involved in the PMA-mediated surface expression of NR2A subunits. Results: NR2A subunits were expressed on the cell membrane after incubation with PMA (200 nmol/L, 30 min), although no functional NMDA channels were detected after PMA-induced membrane trafficking. Immunostaining with an ER marker also revealed that NR2A subunits were exported from the ER after PMA treatment. Furthermore, the deletion of amino acids between 1149-1347 or 1354-1464 of NR2A inhibited PMA-induced surface expression of NR2A subunits. Conclusion: First, our data suggests that PMA treatment can induce the surface expression of homomeric NR2A subunits. Furthermore, this process is probably mediated by the NR2A C-terminal region between positions 1149 and 1464.

Ca2+ release from the endoplasmic reticulum (ER) is an integral component of neuronal Ca2+ signaling. The present study is to investigate properties of local Ca2+ release events in superior cervical ganglion (SCG) neurons. Primary cultured SCG neurons were prepared from neonatal rats (P3-P7). Low concentration of caffeine was used to induce Ca2+ release from the ER Ca2+ store, and intracellular Ca2+was recorded by high-resolution line scan confocal imaging and the Ca2+ indicator Fluo-4. Two populations of local Ca2+ release events with distinct temporal characteristics were evoked by 1.5 mmol/L caffeine near the surface membrane in the soma and the neurites of SCG neurons. Brief events similar to classic Ca2+ sparks lasted a few hundreds of milliseconds, whereas long-lasting events displayed duration up to tens of seconds. Typical somatic and neurite sparks were of 0.3- and 0.52-fold increase in local Fluo-4 fluorescence, respectively. Typical Ca2+ glows were brighter (ΔF/F0 approximately 0.6), but were highly confined in space. The half maximum of full duration of neurite sparks was much longer than those in the soma (685 vs 381 ms). Co-existence of Ca2+ sparks and Ca2+ glows in SCG neurons indicates distinctive local regulation of Ca2+ release kinetics. The local Ca2+ signals of variable, site-specific temporal length may bear important implications in encoding a “memory” of the trigger signal.

Aim: To determine the role of dietary low histamine on the seizure development of pentylenetetrazol (PTZ)-induced kindling in rats. Methods: After 14 d of feeding on a low histamine diet (LH, containing 0.145 μmol/g of histamine), the rats were chemically kindled by repeated intraperitoneal injection of a subconvulsant dose of PTZ (35 mg/kg) once every 48 h, and seizure activity of kindling was recorded for 30 min. Histamine in brain samples was analyzed using a high performance liquid chromatography system with a fluorescence spectrofluorometer. Results: The LH diet induced an increase in seizure response (seizure susceptibility) to the first trial of PTZ, and resulted in facilitation of subsequent PTZ kindling process (seizure development). The histamine levels in the cortex, hippocampus, and hypothalamus of LH-treated rats decreased significantly and these changes correlated well with seizure behavior ( r = 0.875, 0.651, and 0.796, respectively). In addition, chronic kindled seizures resulted in a significant increase of the histamine content in the cortex and hypothalamus in the LH-fed groups. Conclusion: These findings indicate that the histamine in daily food could influence the brain histaminergic function, and play an important role in regulating seizure susceptibility.

Aim: To examine the basic expression levels of N -methyl- D -aspartate (NMDA) receptor NR1 and NR2B subunits in six brain regions of Sprague-Dawley (SD) rats with different visual recognition memory. Methods: Rats were tested by a novelobject- recognition model and grouped into the high and the low visual recognition memory groups. The expression levels of NR1 and NR2B subunits in the cortex, hippocampus, striatum, amygdala, diencephalon, and olfactory bulb were measured by semiquantitative immunoblotting. Results: The NR1 and NR2B subunit protein levels in the hippocampus of the high visual recognition memory group were 35.9% ( P P P Conclusion: The visual recognition memory in rats is related to the basic expression level of NMDA receptor NR1/ NR2B subtype in the hippocampus and striatum.

Aim: To evaluate the effects of global system for mobile communications (GSM) 1800 MHz microwaves on dendritic filopodia, dendritic arborization, and spine maturation during development in cultured hippocampal neurons in rats. Methods: The cultured hippocampal neurons were exposed to GSM 1800 MHz microwaves with 2.4 and 0.8 W/kg, respectively, for 15 min each day from 6 days in vitro (DIV6) to DIV14. The subtle structures of dendrites were displayed by transfection with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on DIV5 into the hippocampal neurons. Results: There was a significant decrease in the density and mobility of dendritic filopodia at DIV8 and in the density of mature spines at DIV14 in the neurons exposed to GSM 1800 MHz microwaves with 2.4 W/kg. In addition, the average length of dendrites per neuron at DIV10 and DIV14 was decreased, while the dendritic arborization was unaltered in these neurons. However, there were no significant changes found in the neurons exposed to the GSM 1800 MHz microwaves with 0.8 W/kg. Conclusion: These data indicate that the chronic exposure to 2.4 W/kg GSM 1800 MHz microwaves during the early developmental stage may affect dendritic development and the formation of excitatory synapses of hippocampal neurons in culture.