Prenatal reduction of E14.5 embryonically fate-mapped pyramidal neurons in a mouse model of autism.

Although several observations suggest that the constitutive biological, genetic or physiological changes leading to autism spectrum disorders (ASD) start in utero, their early impact on the number and density of neurons in the brain remains unknown. Using genetic fate mapping associated with the immunollabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) clearing method we identified and counted a selective population of neocortical and hippocampal pyramidal neurons in the in utero valproate (VPA) mouse model of autism. We report that 1 day before birth, the number of pyramidal neurons born at E14.

Brain Volumes in Mice are Smaller at Birth After Term or Preterm Cesarean Section Delivery.

The rate of cesarean section (CS) delivery has steadily increased over the past decades despite epidemiological studies reporting higher risks of neonatal morbidity and neurodevelopmental disorders. Yet, little is known about the immediate impact of CS birth on the brain, hence the need of experimental studies to evaluate brain parameters following this mode of delivery. Using the solvent clearing method iDISCO and 3D imaging technique, we report that on the day of birth, whole-brain, hippocampus, and striatum volumes are reduced in CS-delivered as compared to vaginally-born mice, with a stronger effect observed in preterm CS pups.

Alteration in the time and/or mode of delivery differentially modulates early development in mice.

Delivery is a complex biological process involving hormonal and mechanical stimuli that together condition the survival and development of the fetus out of the womb. Accordingly, changes in the time or way of being born are associated with an alteration of fundamental biological functions and hypothesized to promote the emergence of neurodevelopmental disorders. Hence, the steadily rise in preterm birth and cesarean section (CS) delivery rates over the past years has become a worldwide health concern.

Enhanced Glutamatergic Currents at Birth in Shank3 KO Mice.

Autism spectrum disorders (ASD) are neurodevelopmental disorders induced by genetic and environmental factors. In our recent studies, we showed that the GABA developmental shifts during delivery and the second postnatal week are abolished in two rodent models of ASD. Maternal treatment around birth with bumetanide restored the GABA developmental sequence and attenuated the autism pathogenesis in offspring.

The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth.

Epidemiological and experimental studies suggest that maternal immune activation (MIA) leads to developmental brain disorders, but whether the pathogenic mechanism impacts neurons already at birth is not known. We now report that MIA abolishes in mice the oxytocin-mediated delivery γ-aminobutyric acid (GABA) shift from depolarizing to hyperpolarizing in CA3 pyramidal neurons, and this is restored by the NKCC1 chloride importer antagonist bumetanide. Furthermore, MIA hippocampal pyramidal neurons at birth have a more exuberant apical arbor organization and increased apical dendritic length than age-matched controls.

Term or Preterm Cesarean Section Delivery Does Not Lead to Long-term Detrimental Consequences in Mice.

Epidemiological studies have provided contradictory data on the deleterious sequels of cesarean section (C-section) delivery and their links with developmental brain disorders such as Autism Spectrum Disorders. To gain better insight on these issues, we have now compared physiological, morphological, and behavioral parameters in vaginal, term, and preterm C-section delivered mice. We report that C-section delivery does not lead to long-term behavioral alterations though preterm C-section delivery modifies communicative behaviors in pups.

Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(-/-) Mouse Model of Parkinson's Disease.

In a preceding study, we showed that in adult pink1(-/-) mice, a monogenic animal model of Parkinson's disease (PD), striatal neurons display aberrant electrical activities that precede the onset of overt clinical manifestations. Here, we tested the hypothesis that the maturation of dopaminergic (DA) neurons of the pink1(-/-) substantia nigra compacta (SNc) follows, from early stages on, a different developmental trajectory from age-matched wild type (wt) SNc DA neurons. We used immature (postnatal days P2-P10) and young adult (P30-P90) midbrain slices of pink1(-/-) mice expressing the green fluorescent protein in tyrosine hydroxylase (TH)-positive neurons.

Response to Comment on "Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring".

Bambini-Junior et al. questioned whether our treatment in two rodent models of autism has a long-lasting effect into adulthood. In response, we show that bumetanide treatment around delivery attenuates autistic behavioral features in adult offspring.

Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes.

Mechanisms and effects of seizures in the immature brain.

The developing immature brain is not simply a small adult brain but rather possesses unique physiological properties. These include neuronal ionic currents that differ markedly from those in the adult brain, typically being longer-lasting and less selective. This enables immature heterogeneous neurons to connect and fire together but at the same time, along with other features may contribute to the enhanced propensity of the developing brain to become epileptic.

Burnout and labour aspects in the nursing teams at two medium-sized hospitals.

Purpose: The aim of this study is to identify the occurrence of Burnout Syndrome (BS) and assess its relationship with different labour-related aspects, among nursing professionals at two medium-sizes hospitals in the city of Cáceres.

Method: This is a transversal and descriptive study, with a sample totalling 141 subjects. As an instrument of research, we used a questionnaire for the limitation of labour-related aspects, with the addition of the Maslach Burnout Inventory (MBI).

Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups.

Midbrain dopaminergic neurons (mDA neurons) are essential for the control of diverse motor and cognitive behaviors. However, our understanding of the activity of immature mDA neurons is rudimentary. Rodent mDA neurons migrate and differentiate early in embryonic life and dopaminergic axons enter the striatum and contact striatal neurons a few days before birth, but when these are functional is not known.

Perspectives on neonatal hypoxia/ischemia-induced edema formation.

Neonatal hypoxia/ischemia (HI) is the most common cause of developmental neurological, cognitive and behavioral deficits in children, with hyperoxia (HHI) treatment being a clinical therapy for newborn resuscitation. Although cerebral edema is a common outcome after HI, the mechanisms leading to excessive fluid accumulation in the brain are poorly understood. Given the rigid nature of the bone-encased brain matter, knowledge of edema formation in the brain as a consequence of any injury, as well as the importance of water clearance mechanisms and water and ion homeostasis is important to our understanding of its detrimental effects.

Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edema.

Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral deficits in children with hyperoxia treatment (HHI) being the current therapy for newborn resuscitation. HI induces cerebral edema that is associated with poor neurological outcomes. Our objective was to characterize cerebral edema after HI and determine the consequences of HHI (40% or 100% O(2)).

Differential regulation of BACE1 promoter activity by nuclear factor-kappaB in neurons and glia upon exposure to beta-amyloid peptides.

The brains of Alzheimer's disease (AD) patients display cerebrovascular and parenchymal deposits of beta-amyloid (A beta) peptides, which are derived by proteolytic processing by the beta-site APP-cleaving enzyme 1 (BACE1) of the amyloid precursor protein (APP). The rat BACE1 promoter has a nuclear factor-kappaB (NF-kappaB) binding site. Deletion studies with a BACE1 promoter/luciferase reporter suggest that the NF-kappaB binding DNA consensus sequence plays a suppressor role, when occupied by NF-kappaB, in the regulation of neuronal brain BACE1 expression.

Rapid assay for quantitative measurement of apoptosis in cultured cells and brain tissue.

Analysis of apoptosis in brain tissue following ischemia, hypoxia, or oxidative stress has technical limitations. The use of counting cells displaying apoptotic morphology is time intensive, vulnerable to sampling errors, and suffers from low numbers of total recorded events. Other cell death assays such as agarose gel analysis of DNA fragmentation, TUNEL, or ELISA are time intensive, limited to a single endpoint measure, and can be technically difficult to perform or reproduce.