Project: ENDOSCHIZO - Precipitation of schizophrenia-like phenotype by prenatal influences: Assessing the role of the endocannabinoid system
Person in Charge: prof. MUDr. Alexandra Šulcová, CSc.
Host Institution: Research group Experimental and Applied Neuropsychopharmacology - Centre for Neuroscience, CEITEC MU
Country of Origin: Italy
Previous Place of Work: USA, Germany
Project duration: 36 months
Panel: Life sciences
Epidemiological studies suggest that heavy Cannabis consumption during pregnancy may represent an important risk factor to adverse neurodevelopmental outcomes as schizophrenia (SCZ) in adulthood, which symptoms lead to severe personal and social dysfunctions. There is therefore a need to assess new potential neurobiological mechanisms to further improve therapeutic interventions. Thus, through an innovative approach we will evaluate carrying out molecular, neurochemical and behavioral studies the degree of endocannabinoid signaling modification in the pathophysiology of SCZ as a neurodevelopmental disorder.
The aim will be achieved by comparing the effects of pre-perinatal Δ9-THC exposure to those induced by the prenatal treatment with the methylazoxymethanol (MAM) acetate, a well validated neurodevelopmental model in rats. Significant attention will be given to the vulnerability of the offspring to develop neonatal behavior deficits as well as a SCZ-like phenotype at different age (from adolescent to adulthood) and how the treatment with novel cannabinoid-related agents could interfere with this phenotype.
The structural changes of several brain regions related to the neurotransmitter system alterations will be correlated to the behavioral responses of the animals and the gender-based difference both to develop SCZ-like symptoms and to the pharmacological treatment will be assessed. Despite the limits of an experimental animal model per se, it is expected that results of this proposal will update our knowledge on the pathophysiological bases of SCZ, as a neurodevelopmental disorder, opening new perspectives to ameliorate the present therapeutic protocols.