BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction
| Autor: | Abraham Weizman, Ran Barzilay, Akira Sawa, Michal Taler, Shay Henry Hornfeld, Atsushi Kamiya, Daniel Offen, Hadar Segal-Gavish, Minae Niwa, Irit Gil-Ad, Yael Barhum, Inna Slutsky, Tali Ben-Zur, Neta Gazit |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Adolescent Hippocampus Nerve Tissue Proteins Mice 03 medical and health sciences Cognition 0302 clinical medicine Neurochemical mental disorders Cannabinoid receptor type 1 Genetics medicine Animals Humans Dronabinol Tetrahydrocannabinol Molecular Biology Genetics (clinical) Effects of cannabis Cognitive deficit Cannabis Brain-derived neurotrophic factor biology Brain-Derived Neurotrophic Factor organic chemicals Articles General Medicine biology.organism_classification 030227 psychiatry Mice Inbred C57BL Disease Models Animal Animals Newborn Psychotic Disorders medicine.symptom Cognition Disorders Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Human Molecular Genetics. 26:2462-2471 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations. Wild-Type and dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests were conducted to assess exploratory activity (open field test, light-dark box test) and cognitive function (novel object recognition test). Electrophysiological effect of THC was evaluated using acute hippocampal slices, and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor (BDNF) protein levels were measured. Our results indicate that THC exposure elicits deficits in exploratory activity and recognition memory, together with reduced short-term synaptic facilitation and loss of BDNF surge in the hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in recognition memory. The results of this study imply that induction of BDNF following adolescence THC exposure may serve as a homeostatic response geared to maintain proper cognitive function against exogenous insult. The BDNF surge in response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1 may be a useful probe to identify biological cascades involved in the neurochemical, electrophysiological, and behavioral effects of cannabis related psychiatric manifestations. |
| Databáze: | OpenAIRE |
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