Environmental exposure to common pesticide induces synaptic deficit and social memory impairment driven by neurodevelopmental vulnerability of hippocampal parvalbumin interneurons.

Environmental exposure to pesticides at levels deemed safe by regulatory agencies has been linked to increased risk for neurodevelopmental disorders. Yet, the mechanisms linking exposure to these disorders remain unclear. Here, we show that maternal exposure to the pesticide deltamethrin (DM) at the no observed adverse effect level (NOAEL) disrupts long-term potentiation (LTP) in the hippocampus of adult male offspring three months after exposure, a phenotype absent in female offspring.

Postmortem CT and MRI for detecting bowel obstruction in cases of pediatric sepsis deaths.

This article describes the utility of postmortem CT and MRI in diagnosing pediatric bowel obstruction (BO) as the cause of septic shock-induced death. Six pediatric cases with confirmed septic shock were retrospectively analyzed. Postmortem CT scans revealed clear signs of BO in all cases, with volvulus, intussusception, diaphragmatic hernia, or Meckel's diverticulum identified.

Repeated diagnostic ultrasound exposure modifies the structural properties of CA1 dendrites and alters the hippocampal transcriptome.

The development of neurons is regulated by several spatiotemporally changing factors, which are crucial to give the ability of neurons to form functional networks. While external physical stimuli may impact the early developmental stages of neurons, the medium and long-term consequences of these influences have yet to be thoroughly examined. Using an animal model, this study focuses on the morphological and transcriptome changes of the hippocampus that may occur as a consequence of fetal ultrasound examination.

TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.

Background: Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes.

Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.

Cocaine use disorder (CUD) is a prevalent neuropsychiatric disorder with few existing treatments. Thus, there is an unmet need for the identification of new pharmacological targets for CUD. Previous studies using environmental enrichment versus isolation paradigms have found that the latter induces increased cocaine self-administration with correlative increases in the excitability of medium spiny neurons (MSN) of the nucleus accumbens shell (NAcSh).

Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.

Glycogen synthase kinase 3β (GSK3) is a multifaceted serine/threonine (S/T) kinase expressed in all eukaryotic cells. GSK3β is highly enriched in neurons in the central nervous system where it acts as a central hub for intracellular signaling downstream of receptors critical for neuronal function. Unlike other kinases, GSK3β is constitutively active, and its modulation mainly involves inhibition via upstream regulatory pathways rather than increased activation.

Inhibition of the Akt/PKB Kinase Increases Na1.6-Mediated Currents and Neuronal Excitability in CA1 Hippocampal Pyramidal Neurons.

In neurons, changes in Akt activity have been detected in response to the stimulation of transmembrane receptors. However, the mechanisms that lead to changes in neuronal function upon Akt inhibition are still poorly understood. In the present study, we interrogate how Akt inhibition could affect the activity of the neuronal Na channels with while impacting intrinsic excitability.

Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability.

The axon initial segment (AIS) is a highly regulated subcellular domain required for neuronal firing. Changes in the AIS protein composition and distribution are a form of structural plasticity, which powerfully regulates neuronal activity and may underlie several neuropsychiatric and neurodegenerative disorders. Despite its physiological and pathophysiological relevance, the signaling pathways mediating AIS protein distribution are still poorly studied.

Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits.

Recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional "remapping" occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel.

Postmortem Computed Tomography and Magnetic Resonance Imaging of Gunshot Wounds to the Neck.

Postmortem magnetic resonance imaging (MRI) is rarely used for the radiologic assessment of gunshot injuries, although it has clear advantages over postmortem computed tomography (CT) with regard to the imaging of soft tissue injuries. Another benefit in using MRI is that lodged projectiles composed of nonferromagnetic material such as lead present only marginal metal artifacts compared with severe artifacts on CT. This case report presents CT and MRI findings in a case with two gunshot wounds to the neck: a perforating wound and a nonperforating wound with a lead bullet lodged in the cervical spine.

CREB controls cortical circuit plasticity and functional recovery after stroke.

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery.

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation.

Dorsoventral differences in Kv7/M-current and its impact on resonance, temporal summation and excitability in rat hippocampal pyramidal cells.

In rodent hippocampi, the connections, gene expression and functions differ along the dorsoventral (D-V) axis. CA1 pyramidal cells show increasing excitability along the D-V axis, although the underlying mechanism is not known. In the present study, we investigated how the M-current (IM ), caused by Kv7/M (KCNQ) potassium channels, and known to often control neuronal excitability, contributes to D-V differences in intrinsic properties of CA1 pyramidal cells.

Synthesis and biological effects of some kynurenic acid analogs.

The overactivation of excitatory amino acid receptors plays a key role in the pathomechanism of several neurodegenerative disorders and in ischemic and post-ischemic events. Kynurenic acid (KYNA) is an endogenous product of the tryptophan metabolism and, as a broad-spectrum antagonist of excitatory amino acid receptors, may serve as a protective agent in neurological disorders. The use of KYNA is excluded, however, because it hardly crosses the blood-brain barrier.

Kainate postconditioning restores LTP in ischemic hippocampal CA1: onset-dependent second pathophysiological stress.

Postconditioning can be induced by a broad range of stimuli within minutes to days after an ischemic cerebral insult. A special form is elicited by pharmacological intervention called second pathophysiological stress. The present study aimed to evaluate the effects of low-dose (5 mg/kg) kainate postconditioning with onsets 0, 24 and 48 h after the ischemic insult on the hippocampal synaptic plasticity in a 2-vessel occlusion model in rat.

Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia.

Global forebrain ischemia results in damage to the pyramids in the CA1 hippocampal subfield, which is particularly vulnerable to excitotoxic processes. Morphological and functional disintegration of this area leads to a cognitive dysfunction and neuropsychiatric disorders. Treatment with N-methyl-d-aspartate receptor antagonists is a widely accepted method with which to stop the advance of excitotoxic processes and concomitant neuronal death.

Effects of blood glutamate scavenging on cortical evoked potentials.

It is well known that traumatic or ischemic brain injury is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) in brain fluids. It has recently been demonstrated that excess Glu can be eliminated from brain into blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to intravenous OxAc administration (i.

A novel kynurenic acid analogue: a comparison with kynurenic acid. An in vitro electrophysiological study.

Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only restricted ability to cross the blood-brain barrier. Accordingly, new kynurenic acid analogues which can readily cross the blood-brain barrier and exert their complex anti-excitotoxic activity are greatly needed.

Oxaloacetate decreases the infarct size and attenuates the reduction in evoked responses after photothrombotic focal ischemia in the rat cortex.

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.

Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion.

Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate.

Kynurenine diminishes the ischemia-induced histological and electrophysiological deficits in the rat hippocampus.

The neuroprotective effect of L-kynurenine sulfate (KYN), a precursor of kynurenic acid (KYNA, a selective N-methyl-D-aspartate receptor antagonist), was studied. KYN (300 mg/kg i.p.

Hippocampal (CA1) activities in Wistar rats from different vendors. Fundamental differences in acute ischemia.

Two-vessel occlusion, a frequently used model of global cerebral ischemia in rats, results in a dysfunction predominantly within the CA1 field of the hippocampus; it induces many processes with different time-scales. However, the great divergence in the results of the studies reported in the literature suggests valuable differences in response to hypoperfusion-induced ischemia among the laboratory rats used in these studies. In the present work, the acute effects of two-carotid occlusion-induced global ischemia (2VO) on the CA3 stimulation-evoked population spike activity in the CA1 region of Wistar rats from different suppliers (Charles-River and Harlan) were compared.

Kynurenine administered together with probenecid markedly inhibits pentylenetetrazol-induced seizures. An electrophysiological and behavioural study.

The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid, which may therefore serve as a protective agent in such neurological disorders as epileptic seizures. Kynurenic acid, however, has a very limited ability to cross the blood-brain barrier, whereas kynurenine passes the barrier easily. In this study, we tested the hypothesis that kynurenine administered systemically together with probenecid, which inhibits kynurenic acid excretion from the cerebrospinal fluid, results in an increased level of kynurenic acid in the brain that is sufficiently high to provide protection against the development of pentylentetrazol-induced epileptic seizures.