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Séminaire - Luis Felipe Callado"The endocannabinoid system and schizophrenia: evidence from human postmortem brain studies"

Abstract :

Pr Luis Felipe CALLADO du Department of Pharmacology,
University of the Basque Country


 Numerous reports have implicated the endocannabinoid system in the pathophysiology of schizophrenia. In this context, studies with human samples are critical to identify how central endocannabinoid ligands/CB1 receptors are altered in patients with schizophrenia. We have recently demonstrated an opposite change in 2-arachidonoylglycerol and anandamide levels in postmortem brain of schizophrenic patients.

This deregulation of both endocannabinoids could alter dopamine and glutamate release in key brain areas that have shown functional alterations in schizophrenia. Additionally, we showed that the immunodensity of CB1 receptors was significantly decreased in the prefrontal cortex of antipsychotic-treated schizophrenic subjects but not in drug-free subjects with schizophrenia. It can be speculated that this decrease in CB1 receptor density in the human prefrontal cortex represents an adaptative mechanism of receptor oligomers that would be beneficial for the treatment of schizophrenia symptoms.  

Selected publications

1.Erdozain A.M.; Rubio M.; Valdizan E.M.; Pazos A.; Meana J.J.; Fernández-Ruíz J.; Alexander SPH; Callado L.F. “The endocannabinoid system is altered in the postmortem prefrontal cortex of alcoholic subjects”. Addiction Biology doi: 10.1111/adb.12160 (2014).

2.Muguruza C.; Lehtonen M.; Aaltonen N.; Morentin B.; Meana J.J.; Callado L.F. “Quantification of endocannabinoids in postmortem brain of schizophrenic subjects”. Schizophrenia Research 148:145-150 (2013).

3.Kurita M.; Holloway T.; García-Bea A.; Kozlenkov A.; Friedman A.K.; Moreno J.L.; Heshmati M.; Golden S.A; Kennedy P.J.; Takahashi N.; Dietz D.M.; Mocci G.; Gabilondo A.M.; Hanks J.; Umali A.; Callado L.F.; Gallitano A.L.; Neve R.L.; Shen L.; Buxbaum J.D.; Han M-H.; Nestler E.J.; Meana J.J.; Russo S.J.; González-Maeso J. “HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity” Nature Neuroscience 15: 1245-1254 (2012).

4.Urigüen L.; García-Fuster M.J.; Callado L.F.; Morentin B.; La Harpe R.; Casadó V.; Lluis C.; Franco R.; García-Sevilla J.A. ; Meana J.J. “Immunodensity and mRNA expression of A2A adenosine, D2 dopamine and CB1 cannabinoid receptors in postmortem frontal cortex of schizophrenic subjects: Effect of antipsychotic treatment”. Psychopharmacology 206:313-324 (2009).

5.González-Maeso J.; Ang R.; Yuen T.; Chan P.; Weisstaub N.V.; López-Giménez J.; Zhou M.; Okawa Y.; Callado L.F.; Milligan G.; Gingrich J.A.; Filizola M.; Meana J.J.; Sealfon S.C. “Identification of a Novel Serotonin/Glutamate Receptor Complex Implicated in Psychosis” Nature 452:93-97 (2008).

Scientific focus :

Dr. Luis F. Callado has 25 years of experience in neurochemical studies and functional responses of receptors to psychoactive drugs. Dr. Callado’s lab is one of the few European groups working on the neurobiological basis of neuropsychiatric disorders using postmortem human brain tissue.

The Neuropsychopharmacology Research Group at the Department of Pharmacology in the University of the Basque Country has been working since 1986 on brain receptors alterations in relation to neuropsychiatric diseases as affective disorders, schizophrenia or Alzheimer’s disease. Actually, our research projects include two different, but complementary approaches.

Firstly we look at the neurobiological basis of neuropsychiatric disorders directly evaluated in postmortem human brain. For this purpose we use radioligand binding assays, immunoblotting and in situ hibridation. We have a brain collection with more than 400 postmortem samples corresponding to subjects with different neuropsychiatric diseases (Depression, schizophrenia, Alzheimer, drug abuse…) and controls from persons died mainly in traffic crashes. Secondly, we perform neurochemical (microdialysis) and behavioural techniques in animals in order to develop new pharmacological treatments for these diseases.