Neuroscience
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Members of the regulator of G protein signaling 7 (RGS7) (R7) family and Gbeta5 form obligate heterodimers that are expressed predominantly in the nervous system. R7-Gbeta5 heterodimers are GTPase-activating proteins (GAPs) specific for Gi/o-class Galpha subunits, which mediate phototransduction in retina and the action of many modulatory G protein-coupled receptors (GPCRs) in brain. ⋯ Furthermore, R7BP and R7 protein accumulation in vivo requires Gbeta5. 2) Expression of R7BP in Neuro2A cells at levels approximating those in brain recruits endogenous RGS7-Gbeta5 complexes to the plasma membrane. 3) R7BP immunoreactivity in brain concentrates in neuronal soma, dendrites, spines or unmyelinated axons, and is absent or low in glia, myelinated axons, or axon terminals. 4) RGS7-Gbeta5-R7BP complexes in brain extracts associate inefficiently with detergent-resistant lipid raft fractions with or without G protein activation. 5) R7BP and Gbeta5 protein levels are upregulated strikingly during the first 2-3 weeks of postnatal brain development. Accordingly, we suggest that R7-Gbeta5-R7BP complexes in the mouse or rat could regulate signaling by modulatory Gi/o-coupled GPCRs in the developing and adult nervous systems.
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Cannabinoids have long been associated with mnemonic deficits. However, existing evidence has generally focused on the effect of cannabinoids when they are delivered prior to task-training, and such findings are confounded by possible drug effects on sensory, motor, and/or motivational systems that support the acquisition and the expression of learning. The present study investigated the effects of the CB1-receptor agonist WIN 55,212-2 (WIN) on memory consolidation in the Morris water maze. ⋯ Rats bilaterally infused with WIN at 2.5 microg and 5 microg (per side) during training spent significantly less time in the target quadrant than vehicle controls on probe trial 4 weeks later, while no difference was seen at 1-week retention. Taken together, our results showed that post-training activation of CB1 receptors in the hippocampus disrupts long-term memory consolidation but has no effect on acquisition and short-term retention. Plausible pharmacological interactions between cannabinoids and other neurotransmitter systems and associated plasticity mechanisms are discussed.
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Calcium entry into the postsynaptic neuron through N-methyl-D-aspartate-type glutamate receptors (NMDARs) triggers the induction of long-term potentiation (LTP), which is considered to contribute to synaptic plasticity and plays a critical role in behavioral learning. We report here that activin, a member of the transforming growth factor-beta (TGF-beta) superfamily, promotes phosphorylation of NMDARs and increases the Ca2+ influx through these receptors in primary cultured rat hippocampal neurons. ⋯ Activin-induced NMDAR activation persists for more than 24 h, which is complimentary to the activation time of NMDARs by brain-derived neurotrophic factor (BDNF). Our results suggest that activin is a unique and powerful potentiator for NMDAR-dependent signaling, which could be involved in the regulatory mechanisms of synaptic plasticity.
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The anesthetic gas nitrous oxide (N2O) and the volatile anesthetic isoflurane (ISO) are commonly used in surgical procedures for human infants and in veterinary and laboratory animal practice to produce loss of consciousness and analgesia. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA) glutamate receptors or potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. In the present study, the question arises whether a relatively low dose of ISO alone or its combination with N2O entails significant risk of inducing enhanced apoptosis. ⋯ However, enhanced apoptotic cell death was apparent when N2O was combined with ISO at exposure durations of 6 h or more. Co-administration of L-carnitine (300 or 500 mg/kg, i.p.) effectively protected neurons from the anesthetic-induced damage. These data indicate that 6 h or more of inhaled anesthetic exposure consisting of a combination of N2O and ISO results in enhanced neuronal apoptosis, and L-carnitine effectively blocks the neuronal apoptosis caused by inhalation anesthetics in the developing rat brain.
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The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. ⋯ Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.