Serotonin Hyperinnervation Abolishes Seizure Susceptibility in<i>Otx2</i>Conditional Mutant Mice

Tripathi, Prem Prakash; Giovannantonio, Luca Giovanni Di; Viegi, Alessandro; Wurst, Wolfgang; Simeone, Antonio; Bozzi, Yuri

doi:10.1523/jneurosci.2208-08.2008

Cited by 26 publications

(18 citation statements)

References 32 publications

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“…The DAB kit (Boster, Wuhan, China) was used for detecting peroxidase activity. Immunohistochemical quantitative analyses were performed as described previously [23] . Three sections at the level of the aortic sinus were examined.…”

Section: Animal Studiesmentioning

confidence: 99%

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE−/− mice possibly via activated STAT3-mediated upregulation of tristetraprolin

Yin

Tang

Tu³

et al. 2013

Acta Pharmacol Sin

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Aim: To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE -/-mice and the underlying mechanisms. Methods: Male ApoE-KO mice were daily injected with LPS (25 μg, sc) or PBS for 4 weeks. The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP. After the animals were killed, blood, livers and aortas were collected for biochemical and histological analyses. For ex vivo experiments, the abdominal cavity macrophages were harvested from each treatment group of mice, and cultured with autologous serum, then treated with LPS. Results: Chronic administration of LPS in ApoE -/-mice significantly increased the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1), increased infiltration of inflammatory cells, and enhanced the development of atherosclerosis. In LPS-challenged mice injected with rAAV-apoA-I-GFP, viral particles and human apoA-I were detected in the livers, total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased, TG and TC were slightly increased. Furthermore, overexpression of apoA-I significantly suppressed the expression of proinflammatory cytokines, reduced the infiltration of inflammatory cells, and decreased the extent of atherosclerotic lesions. Moreover, overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP), and phosphorylation of JAK2 and STAT3 in aortas. In ex vivo mouse macrophages, the serum from mice overexpressing apoA-I significantly increased the expression of TTP, accompanied by accelerated decay of mRNAs of the inflammatory cytokines. Conclusion: ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP.

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Section: Animal Studiesmentioning

confidence: 99%

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE−/− mice possibly via activated STAT3-mediated upregulation of tristetraprolin

Yin

Tang

Tu³

et al. 2013

Acta Pharmacol Sin

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“…In another study too , the administration of PCPA reduced the brain 5‐HT content in whole brain and reduced spontaneous motor activity particularly exploratory activity. Tripathi et al reported that increased brain 5‐HT levels are responsible for seizure resistance in genetically modified mice.…”

Section: Discussionmentioning

confidence: 99%

Parachlorophenylalanine‐induced 5‐HT depletion alters behavioral and brain neurotransmitters levels in 6‐Hz psychomotor seizure model in mice

Jahan

Pillai

Vohora

2017

Fundamemntal Clinical Pharma

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The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, nor-epinephrine (NE), glutamate, and γ-aminobutyric acid (GABA) in the 6-Hz-induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days)-treated mice were given 6-Hz stimulation. Sodium valproate (SVP) (200 mg/kg/day, p.o for 3 days) was used as a reference antiepileptic drug. The behavioral changes induced by 6 Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position were amplified by PCPA. The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels. PCPA facilitated further reduction of endogenous 5-HT and DA levels but not NE, histamine, GABA, and glutamate levels. Pre- and post-treatment with SVP protected the mice from 6-Hz seizures and attenuated PCPA-induced changes in the levels of 5-HT and DA in the mice brain suggesting the protective effect of SVP in the pharmacoresistant model of epilepsy involving mainly serotonergic mechanism. However, the study also suggests modulation of other neurotransmitters both in 6-Hz psychomotor seizures and in the action of SVP against such seizures.

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“…Mutant mice with conditional inactivation of Otx2 in En1-positive mesDA precursors (En1 cre/+ ; Otx2 flox/flox mice) have a reduced number of mesDA neurons [24] ; in these mutants, DAergic precursors loose their identity and undergo a neurotransmitter fate switch, generating serotonin (5-HT) positive neurons [23] . Reduced DA and increased 5-HT levels persist in the forebrain of adult En1 cre/+ ; Otx2 flox/flox mice [28,29] . As a consequence of this persistent 5-HT hyper-innervation, En1 cre/+ ; Otx2 flox/flox mice are resistant to limbic seizures induced by the glutamate agonist kainic-acid (KA) [29] , confirming the crucial role of DA and 5-HTergic systems in controlling neuronal excitability and seizure susceptibility in the limbic system [30,31] (Table 1 and Fig.…”

Section: Otx1mentioning

confidence: 97%

“…Reduced DA and increased 5-HT levels persist in the forebrain of adult En1 cre/+ ; Otx2 flox/flox mice [28,29] . As a consequence of this persistent 5-HT hyper-innervation, En1 cre/+ ; Otx2 flox/flox mice are resistant to limbic seizures induced by the glutamate agonist kainic-acid (KA) [29] , confirming the crucial role of DA and 5-HTergic systems in controlling neuronal excitability and seizure susceptibility in the limbic system [30,31] (Table 1 and Fig. 1).…”

Section: Otx1mentioning

confidence: 97%

Otx genes and seizure susceptibility

Bozzi

Simeone

2014

Mol Cell Epilepsy

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Homeobox-containing transcription factors crucially regulate the patterning and regionalization of the developing nervous system, as well as the proliferation, survival and differentiation of distinct neuronal populations. Altered expression of these factors markedly impacts the structure and function of the embryonic and adult central nervous system (CNS). In both humans and mice, mutations of homeobox genes have been associated to severe syndromes characterized by developmental CNS defects, which often lead to the occurrence of seizures in the adult life. Among homeobox genes, Otx genes (Otx1 and Otx2) are crucially involved in brain regionalization. Our previous work showed that mice lacking Otx1 present cerebral cortex defects and develop epilepsy, whereas mice with conditional deletion or overexpression of Otx2 show profound alterations in midbrain-to-forebrain circuits, which are accompanied by an abnormal response to experimentally-induced seizures. In this brief review, we highlight and discuss the major findings suppporting the role of Otx genes in sculpting midbrain and forebrain circuits involved in epileptogenesis.

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Serotonin Hyperinnervation Abolishes Seizure Susceptibility inOtx2Conditional Mutant Mice

Cited by 26 publications

References 32 publications

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE−/− mice possibly via activated STAT3-mediated upregulation of tristetraprolin

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE−/− mice possibly via activated STAT3-mediated upregulation of tristetraprolin

Parachlorophenylalanine‐induced 5‐HT depletion alters behavioral and brain neurotransmitters levels in 6‐Hz psychomotor seizure model in mice

Otx genes and seizure susceptibility

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