The Role of Ca2+ Permeable AMPA Receptors in Neurodegeneration, Neurotoxicity, and Neuroinflammation.

It is believed that degenerative conditions that give rise to neurological diseases may share an abnormal influx of Ca2+, mainly through glutamate receptors. Current research on the glutamatergic system indicates that the N-methyl-D-aspartate receptor (NMDAR) is not the only receptor permeable to Ca2+. Under certain conditions, α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are able to rapidly and potently mediate a neurotoxic Ca2+ influx. AMPARs are encoded by four genes designated GluR 1-4. The presence of the edited GluA2 subunit makes the heteromeric AMPAR impermeable to Ca2+ (CI-AMPAR's). On the other hand, the lack of GluA2 or disruptions in its post-translational editing result in Ca2+-permeable AMPA receptors (CP-AMPARs). In addition to triggering behavioral changes, the increase in CP-AMPARs is documented in several neurodegenerative, neuroinflammatory and neurotoxic conditions, demonstrating that AMPAR changes may play a role in the emergence and evolution of pathological conditions of the central nervous system (CNS). Seeking to better understand how CP-AMPARs influence CNS neuropathology, and how it may serve as a pharmacological target for future molecules, in this article, we summarize and discuss studies investigating changes in the composition of AMPARs and their cellular and molecular effects, to improve the understanding of the therapeutic potential of the CP-AMPAR in neurodegenerative, neurotoxic and neuroinflammatory diseases.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively-motivated memory in male rats.

Estrogens, particularly 17ß-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERß, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.