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I22 Cannabinoid receptor in hippocampal hippocampus as a potential therapeutic treatment for the cognitive deficits in Huntington dieases
  1. Nadia Di Franco1,2,3,
  2. Analia Bortolozzi4,
  3. Leticia Campo4,
  4. Marc Espina Cortes1,2,3,
  5. Laura Lopez1,2,3,
  6. Silvia Gines Padros1,2,3
  1. 1Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  2. 2Facultat de Medicina, Institut de Neurociències. Universitat de Barcelona, Barcelona, Spain
  3. 3Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
  4. 4Department of Neurochemistry and Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC), Spain

Abstract

Background Cognitive decline (CD) critically limits patient’s life affected by Huntington’s disease (HD). So far, any treatment alleviates the CD. CD in HD is associated with abnormal neuronal plasticity and gliotransmitter alteration, related to astrocyte dysfunctions. Interestingly, recent studies showed an alteration of the cannabinoid system in HD. So far, the cannabinoid receptor CB1R is correlated to cognitive processes and astrocyte-neuron communication, both in health and diseases.

Aim Consequently, we proposed CB1R as a potential target for CD in HD. In particular, we aim to explore CB1R involvement in the hippocampal astrocyte-neuron dysfunction as a possible target to improve the CD in HD.

Methods Accordingly, we quantified CB1R levels in hippocampal tissue from the HD mouse model R6/1 at different ages by western blot. Furthermore, CB1R expression was explored in astrocytes by immunohistochemistry and colocalization studies with GFAP and s100b. Neurotransmitters release from hippocampal primary astrocyte culture was evaluated in basal condition and under the cannabinoid agonist WIN 55,212-2. Finally, we assessed the effect of WIN on hippocampal memory deficits in R6/1 mice.

Results We found:1) CB1R decrease in the hippocampus of males and females mice at different disease stages, 2) CB1R down-expression in different hippocampal subregions and in astrocytes, 3) altered release of neurotransmitters from hippocampal primary culture of R6/1 in basal condition and under WIN treatment, 4) WIN prevention and rescue of hippocampal memory deficits.

Conclusion Those results point out the role of CB1R in astrocyte for the CD in HD and strongly encouraged CB1R for clinical scopes.

  • Cannabinoid receptor
  • astrocyte
  • hippocampus
  • cognitive deficit
  • Huntington’s disease

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