IGF-1 impacts neocortical interneuron connectivity in epileptic spasm generation and resolution.

Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients' brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA.

PAK1 c.1409 T > a (p. Leu470Gln) de novo variant affects the protein kinase domain, leading to epilepsy, macrocephaly, spastic quadriplegia, and hydrocephalus: Case report and review of the literature.

The p-21-activated kinase 1 (PAK1) protein, encoded by the PAK1 gene, is an evolutionarily conserved serine/threonine-protein kinase that regulates key cellular developmental processes. To date, seven de novo PAK1 variants have been reported to cause the Intellectual Developmental Disorder with Macrocephaly, Seizures, and Speech Delay (IDDMSSD). In addition to the namesake features, other common characteristics include structural brain anomalies, delayed development, hypotonia, and dysmorphic features.

A scoping review: urinary markers of metabolic maturation in infants with CHD and the relationship to growth.

Background: Growth failure in infants born with CHD is a persistent problem, even in those provided with adequate nutrition.

Objective: To summarise the published data describing the change in urinary metabolites during metabolic maturation in infants with CHD and identify pathways amenable to therapeutic intervention.

Design: Scoping review.

Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms.

Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.

Methods: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory.

A Role for Insulin-like Growth Factor 1 in the Generation of Epileptic Spasms in a murine model.

Objective: Infantile spasms are associated with a wide variety of clinical conditions, including perinatal brain injuries. We have created a model in which prolonged infusion of tetrodotoxin (TTX) into the neocortex, beginning in infancy, produces a localized lesion and reproduces the behavioral spasms, electroencephalogram (EEG) abnormalities, and drug responsiveness seen clinically. Here, we undertook experiments to explore the possibility that the growth factor IGF-1 plays a role in generating epileptic spasms.

Brain state-dependent high-frequency activity as a biomarker for abnormal neocortical networks in an epileptic spasms animal model.

Objective: Epileptic spasms are a hallmark of a severe epileptic state. A previous study showed neocortical up and down states defined by unit activity play a role in the generation of spasms. However, recording unit activity is challenging in clinical settings, and more accessible neurophysiological signals are needed for the analysis of these brain states.

Acthar® Gel (repository corticotropin injection) dose-response relationships in an animal model of epileptic spasms.

Studies were undertaken to evaluate the effectiveness of Acthar® Gel (repository corticotropin injection [RCI]) in the tetrodotoxin (TTX) model of early-life-induced epileptic spasms. Repository corticotropin injection (RCI) is widely used in the United States to treat infantile spasms. A major component of RCI is N25 deamidated ACTH.

Neocortical Slow Oscillations Implicated in the Generation of Epileptic Spasms.

Objective: Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here.

Methods: In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms.

haploinsufficiency impairs inhibition and mediates key neurological features of encephalopathy.

Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, with the majority affecting postsynaptic apparatuses and much fewer in presynaptic proteins. Syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1) is an essential component of the presynaptic neurotransmitter release machinery. De novo heterozygous pathogenic variants in are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies.

Comprehensive inventory of true flies (Diptera) at a tropical site.

Estimations of tropical insect diversity generally suffer from lack of known groups or faunas against which extrapolations can be made, and have seriously underestimated the diversity of some taxa. Here we report the intensive inventory of a four-hectare tropical cloud forest in Costa Rica for one year, which yielded 4332 species of Diptera, providing the first verifiable basis for diversity of a major group of insects at a single site in the tropics. In total 73 families were present, all of which were studied to the species level, providing potentially complete coverage of all families of the order likely to be present at the site.

Remarkable fly (Diptera) diversity in a patch of Costa Rican cloud forest: Why inventory is a vital science.

Study of all flies (Diptera) collected for one year from a four-hectare (150 x 266 meter) patch of cloud forest at 1,600 meters above sea level at Zurquí de Moravia, San José Province, Costa Rica (hereafter referred to as Zurquí), revealed an astounding 4,332 species. This amounts to more than half the number of named species of flies for all of Central America. Specimens were collected with two Malaise traps running continuously and with a wide array of supplementary collecting methods for three days of each month.

PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network.

Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss of function of repressors such as PTEN, causes epilepsy in humans and animal models, and altered mTOR signaling may contribute to a broad range of neurological diseases. Changes in synaptic transmission have been reported in animal models of PTEN loss; however, the full extent of these changes, and their effect on network function, is still unknown.

The Impact of Electrographic Seizures on Developing Hippocampal Dendrites Is Calcineurin Dependent.

Neurobehavioral abnormalities are commonly associated with intractable childhood epilepsy. Studies from numerous labs have demonstrated cognitive and socialization deficits in rats and mice that have experienced early-life seizures. However, the cellular and molecular mechanisms underlying these effects are unknown.

Reduced abundance and earlier collection of bumble bee workers under intensive cultivation of a mass-flowering prairie crop.

One of the most commonly seeded crops in Canada is canola, a cultivar of oilseed rape (). As a mass-flowering crop grown intensively throughout the Canadian Prairies, canola has the potential to influence pollinator success across tens of thousands of square kilometers of cropland. Bumble bees ( sp.

FAMILY MILICHIIDAE.

This catalog summarizes information on the species of Milichiidae known to occur in Colombia. It includes 6 described species in 3 described genera and 6 undescribed species in two genera, one of which is also undescribed.

Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.

Copy number variations have been frequently associated with developmental delay, intellectual disability and autism spectrum disorders. MECP2 duplication syndrome is one of the most common genomic rearrangements in males and is characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. The broad range of deficits caused by methyl-CpG-binding protein 2 (MeCP2) overexpression poses a daunting challenge to traditional biochemical-pathway-based therapeutic approaches.

The history of efforts to regulate dietary supplements in the USA.

This review examines the emergence of dietary supplements and how the Food and Drug Administration (FDA) attempted to regulate these, beginning with the arrival of vitamins and how these were managed under the 1906 Food and Drugs Act, and ending with the seismic influence of the 1994 Dietary Supplement Health and Education Act (DSHEA). Included are the impact of major laws, key court decisions, and the construction of the FDA's supplement actions and rules from the 1920s to the 1990s for products that were neither drugs nor typical foods. Stiff resistance to the regulations by supplement manufacturers, trade associations, politicians, and especially the public at large is an important part of this story.

Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes.

Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons.

Activation of extracellular regulated kinase and mechanistic target of rapamycin pathway in focal cortical dysplasia.

Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug-resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S(240/244) ), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S(235/236) ) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S(664) ) leading to hyperactive mTOR signaling.

Vigabatrin therapy implicates neocortical high frequency oscillations in an animal model of infantile spasms.

Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs.

A review of the New World Coproica (Diptera: Sphaeroceridae) with a description of 8 new species.

The New World species of Coproica Rondani, 1861 (Diptera: Sphaeroceridae) are reviewed on the basis of over 17,000 examined specimens. The genus is divided into three major clades: the C. acutangula, C.

Catastrophic childhood epilepsy: a recent convergence of basic and clinical neuroscience.

Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments.

How is homeostatic plasticity important in epilepsy?

Maintaining physiological variables within narrow operating limits by homeostatic mechanisms is a fundamental property of most if not all living cells and organisms. In recent years, research from many laboratories has shown that the activity of neurons and neural circuits are also homeostatically regulated. Here, we attempt to apply concepts of homeostasis in general, and more specifically synaptic homeostatic plasticity, to the study of epilepsy.

Early-life seizures result in deficits in social behavior and learning.

Children with epilepsy show a high co-morbidity with psychiatric disorders and autism. One of the critical determinants of a child's behavioral outcome with autism and cognitive dysfunction is the age of onset of seizures. In order to examine whether seizures during postnatal days 7-11 result in learning and memory deficits and behavioral features of autism we administered the inhalant flurothyl to induce seizures in C57BL/6J mice.

Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.

The Pten and Tsc1 genes both encode proteins that repress mechanistic target of rapamycin (mTOR) signaling. Disruption of either gene in the brain results in epilepsy and autism-like symptoms in humans and mouse models, therefore it is important to understand the molecular and physiological events that lead from gene disruption to disease phenotypes. Given the similar roles these two molecules play in the regulation of cellular growth and the overlap in the phenotypes that result from their loss, we predicted that the deletion of either the Pten or Tsc1 gene from autaptic hippocampal neurons would have similar effects on neuronal morphology and synaptic transmission.