Person: Gómez Ruiz, María Sagrario
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First Name
María Sagrario
Last Name
Gómez Ruiz
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Psicología
Department
Psicobiología y Metodología en Ciencias del Comportamiento
Area
Psicobiología
Identifiers
3 results
Search Results
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Item 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 BorcheltSpinocerebellar 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.Item Changes in CB1 and CB2 receptors in the post‐mortem cerebellum of humans affected by spinocerebellar ataxias(British Journal of Pharmacology, 2014) Benito, Cristina; Romero, Julián; Hernández‐Gálvez, Mariluz; Rodríguez Cueto, Carmen Aurora; Fernández Ruiz, José Javier; Gómez Ruiz, María SagrarioBackground and Purpose: Spinocerebellar ataxias are a family of chronic progressive neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. Unlike other motor disorders, the possible role of changes in the endocannabinoid system in the pathogenesis of SCAs has not been investigated. Experimental Approach: The status of cannabinoid receptor type 1 CB1 and cannabinoid receptor type 2 (CB2)) receptors in the post‐mortem cerebellum of SCA patients and controls was investigated using immunohistochemical procedures. Key results: Immunoreactivity for the CB1 receptor, and also for the CB2 receptor, was found in the granular layer, Purkinje cells, neurons of the dentate nucleus and areas of white matter in the cerebellum of SCA patients at levels notably higher than controls. Double-labelling procedures demonstrated co-localization of CB1 and, in particular, CB2 receptors with calbindin, supporting the presence of these receptors in Purkinje neurons. Both receptors also co-localized with Iba-1 and glial fibrillary acidic protein in the granular layer and white matter areas, indicating that they are present in microglia and astrocytes respectively. Conclusions and implications: Our results demonstrate that CB1 and CB2 receptor levels are significantly altered in the cerebellum of SCA patients. Their identification in Purkinje neurons, which are the main cells affected in SCAs, as well as the changes they experienced, suggest that alterations in endocannabinoid receptors may be related to the pathogenesis of SCAs. Therefore, the endocannabinoid system could provide potential therapeutic targets for the treatment of SCAs and its progression.Item Endocannabinoid-Hydrolysing Enzymes in the Post-Mortem Cerebellum of Humans Affected by Hereditary Autosomal Dominant Ataxias(Pathobiology, 2014) Romero, Julián; Hernández Gálvez, María Luz; Rodríguez Cueto, Carmen Aurora; Fernández Ruiz, José Javier; Benito Villalvilla, Cristina; Gómez Ruiz, María SagrarioObjectives: Spinocerebellar ataxias (SCAs) are characterized by a loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. We recently found important changes in cannabinoid CB1 and CB2 receptors in the post-mortem cerebellum of patients affected by different SCAs. Methods: We wanted to further explore this issue by analysing the two major endocannabinoid-hydrolysing enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL), in the post-mortem cerebellum of SCA patients and control subjects. Results: Immunoreactivity for the FAAH and MAGL enzymes was found in the granular layer, in Purkinje cells, in neurons of the dentate nucleus and in areas of white matter in the cerebellum of patients at levels frequently notably higher than those in control subjects. Using double-labelling procedures, we found co-localization of FAAH and MAGL with calbindin, supporting the presence of these enzymes in Purkinje neurons. Conclusions: Degradative endocannabinoid enzymes are significantly increased in the cerebellum of SCA patients, which would presumably lead to reduced endocannabinoid levels. The identification of these enzymes in Purkinje neurons suggests a relationship with the pathogenesis of SCAs and suggests that the endocannabinoid system could provide potential therapeutic targets for the treatment of disease progression in SCAs.