Person:
Rodríguez Cueto, Carmen Aurora

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First Name
Carmen Aurora
Last Name
Rodríguez Cueto
URI
https://hdl.handle.net/20.500.14352/86323
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2011 - 20172
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Author: Ramos Atance, José Antonio × Subject: 61 ×

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Now showing 1 - 2 of 2
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    Prospects for cannabinoid therapies in basal ganglia disorders
    (British Journal of Pharmacology, 2011) Fernández Ruiz, José Javier; Moreno‐Martet, Miguel; Rodríguez Cueto, Carmen Aurora; Palomo‐Garo, Cristina; Gómez Cañas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán Pastor, Manuel; Mechoulam, Raphael; Ramos Atance, José Antonio
    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9‐tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB1 and CB2 receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB2 receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB2 receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up‐regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB2 receptor up‐regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB2 receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB2receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation.
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    Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3
    (PLOS one, 2017) Hernández-Gálvez, Mariluz; Hillard, Cecilia J.; Maciel, Patricia; Valdeolivas, Sara; Rodríguez Cueto, Carmen Aurora; Gómez Ruiz, María Sagrario; Fernández Ruiz, José Javier; Ramos Atance, José Antonio; David R Borchelt
    Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.