The Thalidomide scandal: a long road to justice

Overview: Thalidomide was an over-the-counter ‘wonder drug’, marketed to pregnant women in the 1950s and 1960s to treat morning sickness and anxiety. Lyn Rowe was born in Melbourne in 1962 with no arms and no legs after her mother took the drug during her pregnancy. In 2011, aged 49, Rowe finally won a multimillion-dollar settlement from the Australian distributor of thalidomide. It’s estimated that as many as 10,000 babies worldwide may have been born with deformities because their mothers had taken the drug. Former journalist and Lyn Rowe’s lawyer, Michael Magazanik, has written Silent Shock – a book that unpacks the incredible story of the Rowe family’s struggle against the drug companies who have sought to evade responsibility. Join Magazanik in conversation with Jill Singer for a discussion of justice delayed – and almost denied

A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning

A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca[superscript 2+]-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice). Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP) that was independent of NMDARs and mediated by GluR2-lacking Ca2+-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca[superscript 2+]-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs.National Health and Medical Research Council (Australia) (Grant number 188819)National Institute of Mental Health (U.S.) (grant P50-MH58880)National Science Foundation (U.S.) (grant number 0543651)National Institute of Mental Health (U.S.) (grant number MH609197)National Institute of Mental Health (U.S.) (MH62122

NEUROBIOLOGICAL CORRELATES OF ALPHA-TOCOPHEROL ANTIEPILEPTOGENIC EFFECTS AND microRNA EXPRESSION MODULATION IN A RAT MODEL OF KAINATE-INDUCED SEIZURES

Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings allowed us to postulate an antiepileptogenic potential for α-T in hippocampal excitotoxicity, in line with clinical evidence showing that α-T improves seizure control in drug-resistant patients. To explore neurobiological correlates of the α-T antiepileptogenic role, rats were injected with such vitamin during the latent period starting right after KA-induced SE, and the effects on circuitry excitability, neuroinflammation, neuronal death, and microRNA (miRNA) expression were investigated in the hippocampus. Results show that in α-T-treated epileptic rats, (1) the number of population spikes elicited by pyramidal neurons, as well as the latency to the onset of epileptiform-like network activity recover to control levels; (2) neuronal death is almost prevented; (3) down-regulation of claudin, a blood-brain barrier protein, is fully reversed; (4) neuroinflammation processes are quenched (as indicated by the decrease of TNF-α, IL-1β, GFAP, IBA-1, and increase of IL-6); (5) miR-146a, miR-124, and miR-126 expression is coherently modulated in hippocampus and serum by α-T. These findings support the potential of a timely intervention with α-T in clinical management of SE to reduce epileptogenesis, thus preventing chronic epilepsy development. In addition, we suggest that the analysis of miRNA levels in serum could provide clinicians with a tool to evaluate disease evolution and the efficacy of α-T therapy in SE