Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. ...Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor α in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.
The Search-Coil Magnetometer for MMS Le Contel, O.; Leroy, P.; Roux, A. ...
Space Science Reviews,
03/2016, Letnik:
199, Številka:
1-4
Journal Article, Book Review
Recenzirano
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The tri-axial search-coil magnetometer (SCM) belongs to the FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission (Torbert et al. in Space Sci. Rev. (
2014
), this issue). It ...provides the three magnetic components of the waves from 1 Hz to 6 kHz in particular in the key regions of the Earth’s magnetosphere namely the subsolar region and the magnetotail. Magnetospheric plasmas being collisionless, such a measurement is crucial as the electromagnetic waves are thought to provide a way to ensure the conversion from magnetic to thermal and kinetic energies allowing local or global reconfigurations of the Earth’s magnetic field. The analog waveforms provided by the SCM are digitized and processed inside the digital signal processor (DSP), within the Central Electronics Box (CEB), together with the electric field data provided by the spin-plane double probe (SDP) and the axial double probe (ADP). On-board calibration signal provided by DSP allows the verification of the SCM transfer function once per orbit. Magnetic waveforms and on-board spectra computed by DSP are available at different time resolution depending on the selected mode. The SCM design is described in details as well as the different steps of the ground and in-flight calibrations.
Summary Inflammation is an important factor in the pathophysiology of seizure generation and epileptogenesis. While the role of CNS inflammation is well acknowledged as an important factor in seizure ...pathophysiology, less is known about the role of peripheral inflammation. Systemic inflammation induces a mirror inflammatory response in the brain that might have transient or long-term effects on seizure susceptibility. The focus of our laboratory research is the study of the interaction of systemic inflammatory events with neuronal excitability and seizure susceptibility. In this paper we provide a review of our findings and discuss possible mechanisms.
Peripheral inflammation leads to a number of centrally mediated physiological and behavioral changes. The underlying mechanisms and the signaling pathways involved in these phenomena are not yet well ...understood. We hypothesized that peripheral inflammation leads to increased neuronal excitability arising from a CNS immune response. We induced inflammation in the gut by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to adult male rats. To examine the excitability of the brain in vivo, we administered pentylenetetrazole (PTZ; a GABAergic antagonist) intravenously to evoke clonic seizures. Rats treated with TNBS showed increased susceptibility to PTZ seizures that was strongly correlated with the severity and progression of intestinal inflammation. In vitro hippocampal slices from inflamed, TNBS-treated rats showed increased spontaneous interictal burst firing following application of 4-aminopyridine, indicating increased intrinsic excitability. The TNBS-treated rats exhibited a marked, reversible inflammatory response within the hippocampus, characterized by microglial activation and increases in tumor necrosis factor α (TNFα) levels. Central antagonism of TNFα using a monoclonal antibody or inhibition of microglial activation by i.c.v. injection of minocycline prevented the increase in seizure susceptibility. Moreover, i.c.v. infusion of TNFα in untreated rats for 4 days also increased seizure susceptibility and thus mimicked the changes in seizure threshold observed with intestinal inflammation. Our finding of a microglia-dependent TNFα-mediated increase in CNS excitability provides insight into potential mechanisms underlying the disparate neurological and behavioral changes associated with chronic inflammation.
There are critical postnatal periods during which even subtle interventions can have long-lasting effects on adult physiology. We asked whether an immune challenge during early postnatal development ...can alter neuronal excitability and seizure susceptibility in adults. Postnatal day 14 (P14) male Sprague Dawley rats were injected with the bacterial endotoxin lipopolysaccharide (LPS), and control animals received sterile saline. Three weeks later, extracellular recordings from hippocampal slices revealed enhanced field EPSP slopes after Schaffer collateral stimulation and increased epileptiform burst-firing activity in CA1 after 4-aminopyridine application. Six to 8 weeks after postnatal LPS injection, seizure susceptibility was assessed in response to lithium-pilocarpine, kainic acid, and pentylenetetrazol. Rats treated with LPS showed significantly greater adult seizure susceptibility to all convulsants, as well as increased cytokine release and enhanced neuronal degeneration within the hippocampus after limbic seizures. These persistent increases in seizure susceptibility occurred only when LPS was given during a critical postnatal period (P7 and P14) and not before (P1) or after (P20). This early effect of LPS on adult seizures was blocked by concurrent intracerebroventricular administration of a tumor necrosis factor alpha (TNFalpha) antibody and mimicked by intracerebroventricular injection of rat recombinant TNFalpha. Postnatal LPS injection did not result in permanent changes in microglial (Iba1) activity or hippocampal cytokine IL-1beta (interleukin-1beta) and TNFalpha levels, but caused a slight increase in astrocyte (GFAP) numbers. These novel results indicate that a single LPS injection during a critical postnatal period causes a long-lasting increase in seizure susceptibility that is strongly dependent on TNFalpha.
The profitability of pheasants breeding is influenced by many factors, but eggs quality is considered as the backbone for successful pheasant breeding. The objective of this study was to determine ...and compare various quality characteristics (physical, morphological, and mechanical) of eggs from three pheasant subspecies: common pheasant (Phasianus colchicus colchicus), Mongolian pheasant (Phasianus colchicus mongolicus), and black pheasant (Phasianus colchicus vs. tenebrosus). A total sample of 180 eggs (60 eggs of each pheasant subspecies) was collected from pheasant hens kept in aviaries in their first year of production (43–47 wk of age). The average weight and volume of eggs from common pheasants was significantly lower (P ˂ 0.05) than those from Mongolian and black pheasants. No significant differences between three pheasant subspecies were observed in albumen and yolk weight and percentage, while egg shell weight and percentage were significantly higher (P < 0.01) at eggs from black pheasants. In comparison to eggs from Mongolian and common pheasants, eggs from black pheasants had the thickest shell and the highest shell strength and required highest force to egg breaking. The values of breaking force and other mechanical characteristics depend on the direction of the loading force during egg compression. The data obtained by evaluating certain characteristics of egg quality can be useful to breeders when choosing a pheasant subspecies, as well as for choosing quality eggs for hatching and their storage.
Abstract Viral infections of the CNS and their accompanying inflammation can cause long-term neurological effects, including increased risk for seizures. To examine the effects of CNS inflammation, ...we infused polyinosinic:polycytidylic acid, intracerebroventricularly to mimic a viral CNS infection in 14 day-old rats. This caused fever and an increase in the pro-inflammatory cytokine, interleukin (IL)-1β in the brain. As young adults, these animals were more susceptible to lithium-pilocarpine and pentylenetetrazol-induced seizures and showed memory deficits in fear conditioning. Whereas there was no alteration in adult hippocampal cytokine levels, we found a marked increase in NMDA (NR2A and C) and AMPA (GluR1) glutamate receptor subunit mRNA expression. The increase in seizure susceptibility, glutamate receptor subunits, and hippocampal IL-1β levels were suppressed by neonatal systemic minocycline. Thus, a novel model of viral CNS inflammation reveals pathophysiological relationships between brain cytokines, glutamate receptors, behaviour and seizures, which can be attenuated by anti-inflammatory agents like minocycline.
Cytokines and brain excitability Galic, Michael A; Riazi, Kiarash; Pittman, Quentin J
Frontiers in neuroendocrinology,
01/2012, Letnik:
33, Številka:
1
Journal Article
Recenzirano
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Highlights ► Cytokines are produced in brain in response to a peripheral or brain inflammation. ► Cytokines are also produced during seizure activity. ► Cytokines augment seizure activity and may be ...important in epileptogenesis. ► Cytokines upregulate glutamatergic and downregulate GABAergic synapses.
Neonatal programming of innate immune function Spencer, S J; Galic, M A; Pittman, Q J
American journal of physiology: endocrinology and metabolism,
01/2011, Letnik:
300, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The early life environment can be crucial in influencing the development of an animal's long-term physiology. There is now much evidence to suggest that perinatal challenges to an animal's immune ...system will result in changes in adult rat behavior, physiology, and molecular pathways following a single inflammatory event during development caused by the bacterial endotoxin lipopolysaccharide (LPS). In particular, it is now apparent that neonatal LPS administration can influence the adult neuroimmune response to a second LPS challenge through hypothalamic-pituitary-adrenal axis modifications, some of which are caused by alterations in peripheral prostaglandin synthesis. These pronounced changes are accompanied by a variety of alterations in a number of disparate aspects of endocrine physiology, with significant implications for the health and well-being of the adult animal. In this review, we discuss the newly elucidated mechanisms by which neonatal immune challenge can permanently alter an animal's endocrine and metabolic physiology and the implications this has for various disease states.
A single postnatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), reduces the neuroimmune response to a subsequent LPS exposure in the adult rat. The attenuated fever and ...proinflammatory response is caused by a paradoxical, amplified, early corticosterone response to LPS. Here we identify the mechanisms underlying the heightened corticosterone response to LPS in adults after early life exposure to LPS. In postnatal LPS-treated rats, hypothalamic corticotrophin-releasing hormone mRNA, pituitary proopiomelanocortin mRNA, and circulating adrenocorticotrophic hormone were all increased after adult exposure to LPS without significant modification to hippocampal or hypothalamic glucocorticoid receptor mRNA or protein or vagally mediated afferent signaling to the brain. Postnatal LPS administration did cause a persistent upregulation of the LPS Toll-like receptor-4 (TLR4) mRNA in liver and spleen, but not in brain, pituitary, or adrenal gland. In addition, cyclooxygenase-2 (COX-2), which is a prostaglandin biosynthetic enzyme and is normally undetectable in most peripheral tissue, was constitutively expressed in the liver. Adult immune activation of the upregulated TLR4 and COX-2 caused a rapid, amplified rise in circulating, but not brain, prostaglandin E(2) that induced an early, enhanced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Thus, postnatal LPS reprograms the neuroimmune axis by priming peripheral tissues to create a novel, prostaglandin-mediated activation of the HPA axis brought about by increased constitutive expression of TLR4 and COX-2.
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