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Fatty acid-binding protein 7 gene deletion promotes decreases in brain cannabinoid type 1 receptor binding
Huy Lu1, Nicole Roeder2, Brittany Richardson2
1Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY, USA.
Abstract:
Fatty acid-binding protein 7 (FABP7) aids in the intracellular transport of endogenous cannabinoids and is involved in regulating the stress response system. This study examined the role of FABP7 in chronic stress exposure through the binding of CB1 receptors. Adult male FABP7+/+ and FABP7-/- mice were treated with the unpredictable chronic mild stress (UCMS) procedure. After 28 days of treatment, mice were euthanized, and CB1 was measured with in vitro autoradiography using [3H] SR141716A. FABP7-/- mice, irrespective of stress treatment, showed reduced [3H] SR141716A binding in the amygdala, secondary somatosensory cortex, and ventral caudate putamen compared with the FABP7+/+ mice. Additionally, FABP7-/- mice treated with UCMS exhibited a reduction in CB1 binding in the globus pallidus and ventral caudate putamen compared with UCMS-treated FABP7+/+ mice. Genetic deletion of FABP7 can decrease CB1 expression in various brain regions; however, the underlying mechanism remains unclear.
Insights
Fatty acid-binding protein 7 (FABP7) deletion reduces cannabinoid receptor 1 (CB1) binding in the brain, impacting stress response. This suggests FABP7 plays a role in regulating CB1 expression and function.
Area of Science:
- Neuroscience
- Molecular Biology
- Stress Research
Background:
- Fatty acid-binding protein 7 (FABP7) facilitates endogenous cannabinoid transport.
- FABP7 is implicated in the regulation of the stress response system.
- Cannabinoid receptor 1 (CB1) is a key component of the endocannabinoid system and stress regulation.
Purpose of the Study:
- To investigate the role of FABP7 in chronic stress exposure.
- To examine the influence of FABP7 on CB1 receptor binding in the brain under stress conditions.
Main Methods:
- Adult male FABP7 wild-type (FABP7+/+) and knockout (FABP7-/-) mice were subjected to unpredictable chronic mild stress (UCMS) for 28 days.
- CB1 receptor binding was quantified using in vitro autoradiography with [3H] SR141716A.
- Brain regions analyzed included the amygdala, secondary somatosensory cortex, ventral caudate putamen, and globus pallidus.
Main Results:
- FABP7-/- mice exhibited reduced [3H] SR141716A binding in the amygdala, secondary somatosensory cortex, and ventral caudate putamen compared to FABP7+/+ mice, regardless of stress.
- UCMS-treated FABP7-/- mice showed further reductions in CB1 binding in the globus pallidus and ventral caudate putamen compared to UCMS-treated FABP7+/+ mice.
- Genetic deletion of FABP7 demonstrably decreases CB1 expression in multiple brain areas.
Conclusions:
- FABP7 plays a significant role in modulating CB1 receptor expression and binding in specific brain regions.
- The absence of FABP7 alters baseline CB1 receptor levels and exacerbates stress-induced changes in CB1 binding.
- Further research is needed to elucidate the precise molecular mechanisms by which FABP7 influences CB1 expression.
