Gómez Murcia, Victoria

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Gómez Murcia, Victoria

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Gómez Murcia, Victoria

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Universidad de Murcia. Departamento de Farmacología

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Open Access
Dopamine D3 receptor blockade accelerates the extinction of opioid withdrawal-induced drug-seeking behaviours and alters microglia in dopaminoceptive nuclei
(2025-05-21) Franco García, Aureliio; Gómez Murcia, Victoria; Milanés Maquilón, María Victoria; Núñez Parra, Cristina; Farmacología
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Both idebenone and idebenol are localized near the lipid-water interface of the membrane and increase its fluidity.
(2016-06-01) Torrecillas, Alejandro; de Godos, Ana M; Gómez-Fernández, Juan C; Gómez Murcia, Victoria; Corbalán García, Senena; Bioquímica y Biología Molecular A
Idebenone is a synthetic analog of coenzyme Q; both share a quinone moiety but idebenone has a shorter lipophilic tail ending with a hydroxyl group. Differential scanning calorimetry experiments showed that both idebenone and idebenol widened and shifted the phase transition of 1,2-dipalmitoylphosphatidylcholine (DPPC) to a lower temperature and a phase separation with different concentrations of these molecules was observed. Also small angle X-ray diffraction and wide angle X-ray diffraction revealed that both, idebenone and idebenol, induced laterally separated phases in fluid membranes when included in DPPC membranes. Electronic profiles showed that both forms, idebenone and idebenol, reduced the thickness of the fluid membrane. (2)H NMR measurements showed that the order of the membrane decreased at all temperatures in the presence of idebenone or idebenol, the greatest disorder being observed in the segments of the acyl chains close to the lipid-water interface. (1)H NOESY MAS NMR spectra were obtained using 1-palmitoyl-2-oleoyl-phosphatidylcholine membranes and results pointed to a similar location in the membrane for both forms, with the benzoquinone or benzoquinol rings and their terminal hydroxyl group of the hydrophobic chain located near the lipid/water interface of the phospholipid bilayer and the terminal hydroxyl group of the hydrophobic chain of both compounds located at the lipid/water interface. Taken together, all these different locations might explain the different physiological behavior shown by the idebenone/idebenol compared with the ubiquinone-10/ubiquinol-10 pair in which both compounds are differently localized in the membrane.
Open Access
Editorial: Exploring prevention strategies and treatment in addictive disorders.
(2024-07-04) Montagud-Romero, Sandra; Gómez Murcia, Victoria; Fernández Gómez, Francisco José; Núñez Parra, Cristina; Farmacología
Open Access
Neuronal A2A receptor exacerbates synapse loss and memory deficits in APP/PS1 mice.
(2024-08-01) Launay, Agathe; Carvalho, Kévin; Burgard, Anaëlle; Meriaux, Céline; Caillierez, Raphaëlle; Eddarkaoui, Sabiha; Kilinc, Devrim; Siedlecki-Wullich, Dolores; Besegher, Mélanie; Bégard, Séverine; Thiroux, Bryan; Jung, Matthieu; Nebie, Ouada; Wisztorski, Maxence; Déglon, Nicole; Montmasson, Claire; Bemelmans, Alexis-Pierre; Hamdane, Malika; Lebouvier, Thibaud; Vieau, Didier; Fournier, Isabelle; Buee, Luc; Lévi, Sabine; Lopes, Luisa V; Boutillier, Anne-Laurence; Faivre, Emilie; Blum, David; Gómez Murcia, Victoria; Farmacología
Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer's disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice developing AD-like amyloidogenesis. Our findings revealed that the early upregulation of A2AR in the presence of an ongoing amyloid pathology exacerbates memory impairments of APP/PS1 mice. These behavioural changes were not linked to major change in the development of amyloid pathology but rather associated with increased phosphorylated tau at neuritic plaques. Moreover, proteomic and transcriptomic analyses coupled with quantitative immunofluorescence studies indicated that neuronal upregulation of the receptor promoted both neuronal and non-neuronal autonomous alterations, i.e. enhanced neuroinflammatory response but also loss of excitatory synapses and impaired neuronal mitochondrial function, presumably accounting for the detrimental effect on memory. Overall, our results provide compelling evidence that neuronal A2AR dysfunction, as seen in the brain of patients, contributes to amyloid-related pathogenesis and underscores the potential of A2AR as a relevant therapeutic target for mitigating cognitive impairments in this neurodegenerative disorder.
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A comparison of the location in membranes of curcumin and curcumin-derived bivalent compounds with potential neuroprotective capacity for Alzheimer’s disease
(Elsevier, 2021-03) Ausili, Alessio; Gómez Murcia, Victoria; Candel, Adela M.; Beltrán, Andrea; Torrecillas, Alejandro; He, Liu; Jiang, Yuqi; Zhang, Shijun; Teruel Puche, José Antonio; Gómez Fernández, Juan C.; Bioquímica y Biología Molecular A
Curcumin and two bivalent compounds, namely 17MD and 21MO, both obtained by conjugation of curcumin with a steroid molecule that acts as a membrane anchor, were comparatively studied. When incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine the compounds showed a very limited solubility in the model membranes. Curcumin and the two bivalent compounds were also incorporated in membranes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and quenching the fluorescence of pure curcumin or of the curcumin moiety in the bivalent compounds by acrylamide it was seen that curcumin was accessible to this water soluble quencher but the molecule was somehow located in a hydrophobic environment. This was confirmed by quenching with doxyl-phosphatidylcholines, indicating that the curcumin moieties of 17MD and 21MO were in a more polar environment than pure curcumin itself. 1H NOESY MAS-NMR analysis supports this notion by showing that the orientation of curcumin was parallel to the plane of the membrane surface close to C2 and C3 of the fatty acyl chains, while the curcumin moiety of 17MD and 21MO positioned close to the polar part of the membrane with the steroid moiety in the centre of the membrane. Molecular dynamics studies were in close agreement with the experimental results with respect to the likely proximity of the protons studied by NMR and show that 17MD and 21MO have a clear tendency to aggregate in a fluid membrane. The anchorage of the bivalent compounds to the membrane leaving the curcumin moiety near the polar part may be very important to facilitate the bioactivity of the curcumin moiety when used as anti-Alzheimer drugs.
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Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL/6J morphine-dependent mice than in Swiss: Role of HPA axis.
(Elsevier, 2021-01-02) Navarro Zaragoza, Javier; Martínez Laorden, Elena; Teruel Fernández, Francisco Javier; Gómez Murcia, Victoria; Cánovas Cabanes, Alberto; Milanés Maquilón, María Victoria; Laorden Carrasco, María Luisa; Almela Rojo, Pilar; Farmacología
Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice. The animals were rendered dependent on morphine by i.p. injection of increasing doses of morphine (10–60 mg/kg). The negative state associated with naloxone (1 mg/kg s.c.) precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. B6 mice obtained a higher aversion score and took longer to extinguish the aversive memory than Swiss mice. In addition, corticosterone levels were increased after CPA expression. Moreover, corticosterone levels were decreased during CPA extinction in Swiss mice without changes in B6 mice. Pre-treatment with the selective CRF1 receptor antagonist CP-154,526 before naloxone, impaired morphine-withdrawal aversive memory acquisition and decreased the extinction period. CP-154,526 also antagonized the increased levels of corticosterone observed after CPA expression in Swiss mice, without any changes in B6 mice. These results indicate that HPA axis could be a critical factor governing opioid withdrawal memory storage and retrieval, but in a strain or stock-specific manner. The differences observed between Swiss and B6 mice suggest that the treatment of addictive disorders should consider different individual predisposition to associate the aversive learning with the context.
Open Access
Upregulation of adenosine A2A receptor in astrocytes is sufficient to trigger hippocampal multicellular dysfunctions and memory deficits.
(2024) Launay, Agathe; Carvalho, Kevin; Genin, Athenais; Gauvrit, Thibaut; Nobili, Paola; Augustin, Emma; Burgard, Anaëlle; Gambi, Johanne; Fourmy, Deborah; Thiroux, Bryan; Vieau, Didier; Bemelmans, Alexis-Pierre; Le Gras, Stephanie; Buee, Luc; Orr, Miranda E; Audinat, Etienne; Boutillier, Anne-Laurence; Bonvento, Gilles; Cambon, Karine; Faivre, Emilie; Blum, David; Gómez Murcia, Victoria; Farmacología
Adenosine is an ubiquitous neuromodulator that ensures cerebral homeostasis. It exerts numerous functions through the activation of G-protein-coupled adenosine receptors (ARs), in particular A (AR) and A (AR) receptors. Interestingly, AR levels are upregulated in cortical and hippocampal regions in several pathological conditions such as Alzheimer's disease, tauopathies or epilepsia. Such abnormal upregulations have been particularly reported in astrocytes, glial cells that play a key role in regulating synaptic plasticity. However, the overall impact and the underlying mechanisms associated with increased AR in astrocytes remain poorly understood. In the present study, we induced the upregulation of AR in hippocampal astrocytes using dedicated AAVs and comprehensively evaluated the functional consequences in 4 months-old C57Bl6/J mice. Our results show that AR upregulation primarily promotes alterations of astrocyte reactivity, morphology and transcriptome, with a link to aging-like phenotype as well as secondary impairments of neuronal excitability and microglial phenotype. These changes driven by a restricted AR upregulation in hippocampal astrocytes were sufficient to induce impairments of short-term spatial memory and spatial learning. This study highlights the impact of astrocytic AR upregulation, as seen in various neurological conditions, on the development of a detrimental multicellular response associated with memory alterations and provides an additional proof-of-concept for the value of targeting this receptor in different neurodegenerative conditions.
Open Access
Regulation of glial markers expression in the rat basolateral amygdala and hippocampus during morphine aversive memory retrieval and its extinction
(2025-12-15) Franco García, Aureliio; Gómez Murcia, Victoria; Núñez Parra, Cristina; Farmacología
Background Opioid use disorder is driven by neurobehavioral adaptations where environmental cues trigger relapse. Consequently, extinction therapy (ET) aims to modify drug-associated memories but has limited long-term efficacy. Recently, evidence suggested that glial cells may contribute to neuroplasticity phenomena in addiction. In this sense, this study examined whether aversive memories of morphine withdrawal and their extinction induce transcriptional changes in glial markers (gfap, aif1, itgam, klf4) in key memory-related regions: the basolateral amygdala (BLA) and hippocampus (dentate gyrus [DG] and CA1). Results Using the conditioned place aversion (CPA) paradigm in rats, we assessed avoidance behavior after naloxone-precipitated withdrawal and its extinction. Transcriptional analyses did not reveal major changes in the BLA. However, in CA1, downregulation of microglial markers cooccurred with aversive memory retrieval and restored after extinction. Moreover, one of the microglial markers, klf4, was reduced concomitantly with extinction memory retrieval in the DG. Correlation analyses showed negative associations between microglial markers and aversive memory strength, suggesting glial involvement in withdrawal-related learning. Conclusions These findings might indicate that microglial activity in CA1 plays a role in opioid withdrawal-associated memories, and extinction training might be returning these effects to basal levels. Therefore, targeting glial responses could provide new therapeutic strategies to prevent relapse.