2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors
Abstract Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory...
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doaj-70f2925773ac4daa8f816652716a2dda2021-02-14T12:25:53ZengBMCMolecular Brain1756-66062021-02-0114112410.1186/s13041-020-00724-z2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptorsSerena Boccella0Francesca Guida1Monica Iannotta2Fabio Arturo Iannotti3Rosmara Infantino4Flavia Ricciardi5Claudia Cristiano6Rosa Maria Vitale7Pietro Amodeo8Ida Marabese9Carmela Belardo10Vito de Novellis11Salvatore Paino12Enza Palazzo13Antonio Calignano14Vincenzo Di Marzo15Sabatino Maione16Livio Luongo17Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Institute of Biomolecular Chemistry, CNRDepartment of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Pharmacy, School of Medicine, University of Naples Federico IIInstitute of Biomolecular Chemistry, CNRInstitute of Biomolecular Chemistry, CNRDepartment of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Pharmacy, School of Medicine, University of Naples Federico IIInstitute of Biomolecular Chemistry, CNRDepartment of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”Abstract Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target molecules might be a promising therapeutic strategy against the symptoms associated with NP. 2-pentadecyl-2-oxazoline (PEA-OXA) is a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders. The molecular mechanisms by which PEA-OXA exerts its effects are, however, only partially known. In the current study, we show that PEA-OXA, besides being an alpha2 adrenergic receptor antagonist, also acts as a modulator at histamine H3 receptors, and report data on its effects on sensory, affective and cognitive symptoms associated with the spared nerve injury (SNI) model of neuropathic pain in mice. Treatment for 14 days with PEA-OXA after the onset of the symptoms associated with neuropathic pain resulted in the following effects: (i) allodynia was decreased; (ii) affective/cognitive impairment associated with SNI (depression, spatial, and working memories) was counteracted; (iii) long-term potentiation in vivo in the lateral entorhinal cortex-dentate gyrus (perforant pathway, LPP) was ameliorated, (iv) hippocampal glutamate, GABA, histamine, norepinephrine and dopamine level alterations after peripheral nerve injury were reversed, (v) expression level of the TH positive neurons in the Locus Coeruleus were normalized. Thus, a 16-day treatment with PEA-OXA alleviates the sensory, emotional, cognitive, electrophysiological and neurochemical alterations associated with SNI-induced neuropathic pain.https://doi.org/10.1186/s13041-020-00724-zNeuropathic painDepressionCognitive impairmentsH3 receptorsLocus coeruleusMice |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Serena Boccella Francesca Guida Monica Iannotta Fabio Arturo Iannotti Rosmara Infantino Flavia Ricciardi Claudia Cristiano Rosa Maria Vitale Pietro Amodeo Ida Marabese Carmela Belardo Vito de Novellis Salvatore Paino Enza Palazzo Antonio Calignano Vincenzo Di Marzo Sabatino Maione Livio Luongo |
spellingShingle |
Serena Boccella Francesca Guida Monica Iannotta Fabio Arturo Iannotti Rosmara Infantino Flavia Ricciardi Claudia Cristiano Rosa Maria Vitale Pietro Amodeo Ida Marabese Carmela Belardo Vito de Novellis Salvatore Paino Enza Palazzo Antonio Calignano Vincenzo Di Marzo Sabatino Maione Livio Luongo 2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors Molecular Brain Neuropathic pain Depression Cognitive impairments H3 receptors Locus coeruleus Mice |
author_facet |
Serena Boccella Francesca Guida Monica Iannotta Fabio Arturo Iannotti Rosmara Infantino Flavia Ricciardi Claudia Cristiano Rosa Maria Vitale Pietro Amodeo Ida Marabese Carmela Belardo Vito de Novellis Salvatore Paino Enza Palazzo Antonio Calignano Vincenzo Di Marzo Sabatino Maione Livio Luongo |
author_sort |
Serena Boccella |
title |
2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors |
title_short |
2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors |
title_full |
2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors |
title_fullStr |
2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors |
title_full_unstemmed |
2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors |
title_sort |
2-pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and h3 histamine autoreceptors |
publisher |
BMC |
series |
Molecular Brain |
issn |
1756-6606 |
publishDate |
2021-02-01 |
description |
Abstract Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target molecules might be a promising therapeutic strategy against the symptoms associated with NP. 2-pentadecyl-2-oxazoline (PEA-OXA) is a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders. The molecular mechanisms by which PEA-OXA exerts its effects are, however, only partially known. In the current study, we show that PEA-OXA, besides being an alpha2 adrenergic receptor antagonist, also acts as a modulator at histamine H3 receptors, and report data on its effects on sensory, affective and cognitive symptoms associated with the spared nerve injury (SNI) model of neuropathic pain in mice. Treatment for 14 days with PEA-OXA after the onset of the symptoms associated with neuropathic pain resulted in the following effects: (i) allodynia was decreased; (ii) affective/cognitive impairment associated with SNI (depression, spatial, and working memories) was counteracted; (iii) long-term potentiation in vivo in the lateral entorhinal cortex-dentate gyrus (perforant pathway, LPP) was ameliorated, (iv) hippocampal glutamate, GABA, histamine, norepinephrine and dopamine level alterations after peripheral nerve injury were reversed, (v) expression level of the TH positive neurons in the Locus Coeruleus were normalized. Thus, a 16-day treatment with PEA-OXA alleviates the sensory, emotional, cognitive, electrophysiological and neurochemical alterations associated with SNI-induced neuropathic pain. |
topic |
Neuropathic pain Depression Cognitive impairments H3 receptors Locus coeruleus Mice |
url |
https://doi.org/10.1186/s13041-020-00724-z |
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