Long-Interval Intracortical Inhibition and the Cortical Silent Period in Youth.

Background: The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABA)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths.

Methods: We analyzed data from three previous studies of youth who underwent CSP and LICI measurements with transcranial magnetic stimulation and electromyography.

Efficacy and safety of lamotrigine in pediatric mood disorders: A systematic review.

Aim: To appraise the current evidence on the efficacy and safety of lamotrigine (LAM) in the treatment of pediatric mood disorders (PMD) (i.e., Major Depressive disorder [MDD], bipolar disorder [BD]).

Mental Health Clinical Research Innovations during the COVID-19 Pandemic: The Future Is Now.

The COVID-19 pandemic put an unprecedented strain on clinical research worldwide. As in-person clinical trials came to a screeching halt, we sought new ways to move forward, or as Bob Dylan put it, "start swimmin' or sink like a stone." Telemedicine has long been a part of medicine and clinical research, but fully remote clinical trials were few and far between.

Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.

RHO (Rod opsin) encodes a G-protein coupled receptor that is expressed exclusively by rod photoreceptors of the retina and forms the essential photopigment, rhodopsin, when coupled with 11-cis-retinal. Many rod opsin disease -mutations cause rod opsin protein misfolding and trigger endoplasmic reticulum (ER) stress, leading to activation of the Unfolded Protein Response (UPR) signal transduction network. Chop is a transcriptional activator that is induced by ER stress and promotes cell death in response to chronic ER stress.

Glutamatergic neurotransmission from melanopsin retinal ganglion cells is required for neonatal photoaversion but not adult pupillary light reflex.

Melanopsin-expressing retinal ganglion cells (mRGCs) in the eye play an important role in many light-activated non-image-forming functions including neonatal photoaversion and the adult pupillary light reflex (PLR). MRGCs rely on glutamate and possibly PACAP (pituitary adenylate cyclase-activating polypeptide) to relay visual signals to the brain. However, the role of these neurotransmitters for individual non-image-forming responses remains poorly understood.

Induction of endoplasmic reticulum stress genes, BiP and chop, in genetic and environmental models of retinal degeneration.

Purpose: Endoplasmic reticulum (ER) stress has been observed in animal models of retinitis pigmentosa expressing P23H rhodopsin. We compared levels of tightly induced ER stress genes, Binding of immunoglobulin protein (BiP) and CCAAT/enhancer-binding protein homologous protein (Chop), in seven additional models of retinal degeneration arising from genetic or environmental causes.

Methods: Retinas from transgenic S334ter rhodopsin (lines 3, 4, and 5) and Royal College of Surgeons (RCS and RCS-p+) rats from postnatal (P) days 10 to 120 were analyzed.

Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease.

Purpose: To assess structural, functional, and visual behavioral relationships in mutant rhodopsin transgenic (Tg) rats and to determine whether early optokinetic tracking (OKT) visual experience, known to permanently elevate visual thresholds in normal rats, can enhance vision in rats with photoreceptor degeneration.

Methods: Eight lines of pigmented Tg rats and RCS rats were used in this study. OKT thresholds were tested at single ages (1, 2, 3, 4, and 6 months) in naïve groups of rats, or daily in groups that began at eye-opening (P15) or 10 days later (P25).

Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.

Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors.

Ceramide signaling in retinal degeneration.

Retinal degenerations (RD) are a complex heterogeneous group of diseases in which retinal photoreceptors and the supporting retinal pigment epithelial cells die irreversibly, causing visual loss for millions of people. Mutations on more than 150 genes have been discovered for RD and there are many forms that possess complex etiology involving more than one gene and environmental effect. For years many have searched for some common intracellular second messenger for these many forms of cell death which could be targeted for therapy.

mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice.

Retinal pigment epithelial (RPE) cell dysfunction plays a central role in various retinal degenerative diseases, but knowledge is limited regarding the pathways responsible for adult RPE stress responses in vivo. RPE mitochondrial dysfunction has been implicated in the pathogenesis of several forms of retinal degeneration. Here we have shown that postnatal ablation of RPE mitochondrial oxidative phosphorylation in mice triggers gradual epithelium dedifferentiation, typified by reduction of RPE-characteristic proteins and cellular hypertrophy.

Genetic modifiers of retinal degeneration in the rd3 mouse.

Purpose: In previous studies of light-induced (LRD) and age-related (ageRD) retinal degeneration (RD) between the BALB/cByJ (BALB) and B6(Cg)-Tyr(c-2J)/J (B6a) albino mouse strains, RD-modifying quantitative trait loci (QTLs) were identified. After breeding BALB- and B6a-rd3/rd3 congenic strains and finding significant differences in RD, an F1 intercross to determine rd3 QTLs that influence this inherited RD was performed.

Methods: N10, F2 BALB- and B6a-rd3/rd3 strains were measured for retinal outer nuclear layer (ONL) thickness from 5 to 12 weeks of age.