Noradrenaline and Seizures: A Perspective on the Role of Adrenergic
Receptors in Limbic Seizures

Biagioni, Francesca; Celli, Roberta; Puglisi‐Allegra, Stefano; Nicoletti, Ferdinando; Giorgi, Filippo Sean; Fornai, Francesco

doi:10.2174/1570159x20666220327213615

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Norepinephrine exerts its anticonvulsant effects through β2-adrenergic receptors by stimulating the autophagy pathway. Noradrenergic fibers originating from the locus coeruleus densely innervate limbic structures, including the piriform cortex, which represents the limbic structure with the lowest seizure threshold [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

et al. 2022

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Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and γ-aminobutyric acid (GABA)A receptors in vivo in the brain using positron emission tomography (PET) imaging and 11C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of 11C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABAA receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway.

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Section: Discussionmentioning

confidence: 99%

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

et al. 2022

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“…The plasticityinducing effects of LC are extended to a variety of physiological and pathological conditions (Fornai et al, 2011;Galgani et al, 2020;Gesi et al, 2000;Giorgi et al, 2003;Giorgi et al, 2006;Giorgi et al, 2008;Giorgi et al, 2017;Giorgi et al, 2019;Giorgi et al, 2020a;Giorgi et al, 2020b;Giorgi et al, 2021a;Giorgi et al, 2021b;Giorgi et al, 2022;Ruffoli et al, 2011), which include learning and memory and seizures. In all these cases a prominent role is exerted by beta receptors, which modulate specific intracellular signaling pathways (Lazzeri et al, 2021;Biagioni et al, 2022). The role of LC in photic plasticity emerged in the study by Watabe et al, (1982), who showed activation of the reticular nucleus LC following the stimulation of both geniculate and extra-geniculate pathways including: the optic chiasm (OX), the dorsal lateral geniculate nucleus (LGN), the superior colliculus (SC), and the visual cortex (VC).…”

Section: The Effects Of Light Exposure On Plasticity Of Vegetative An...mentioning

confidence: 99%

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity

Pinelli¹,

Bucci

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

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The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periaqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.

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“…In particular, NE axons arising from LC (LC-NE) protect against neuronal damage in a variety of degenerative disorders [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. This evidence encompasses acute neurological insults, such as epileptic seizures [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], brain ischemia [ 34 , 35 , 36 ], and chronic degenerative disorders. In fact, the protective effects of LC are mostly evident at disease onset and during the course of chronic neurodegeneration, such as experimental Parkinsonism induced in rodents [ 37 , 38 , 39 ] and monkeys [ 40 ], as well as in persons affected by Parkinson’s disease (PD) [ 12 , 41 , 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

Biagioni,

Ferrucci,

Lazzeri

et al. 2024

IJMS

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The present investigation was designed based on the evidence that, in neurodegenerative disorders, such as Alzheimer’s dementia (AD) and Parkinson’s disease (PD), damage to the locus coeruleus (LC) arising norepinephrine (NE) axons (LC-NE) is documented and hypothesized to foster the onset and progression of neurodegeneration within target regions. Specifically, the present experiments were designed to assess whether selective damage to LC-NE axons may alter key proteins involved in neurodegeneration within specific limbic regions, such as the hippocampus and piriform cortex, compared with the dorsal striatum. To achieve this, a loss of LC-NE axons was induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) in C57 Black mice, as assessed by a loss of NE and dopamine-beta-hydroxylase within target regions. In these experimental conditions, the amount of alpha-synuclein (alpha-syn) protein levels were increased along with alpha-syn expressing neurons within the hippocampus and piriform cortex. Similar findings were obtained concerning phospho-Tau immunoblotting. In contrast, a decrease in inducible HSP70-expressing neurons and a loss of sequestosome (p62)-expressing cells, along with a loss of these proteins at immunoblotting, were reported. The present data provide further evidence to understand why a loss of LC-NE axons may foster limbic neurodegeneration in AD and limbic engagement during PD.

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Noradrenaline and Seizures: A Perspective on the Role of Adrenergic Receptors in Limbic Seizures

Cited by 4 publications

References 26 publications

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity

Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

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