Environmental enrichment sex-dependently rescues memory impairment in FABP5 KO mice not mediated by brain-derived neurotrophic factor

Fatty acid-binding protein 5 differentially impacts dopamine signaling independent of sex and environment

“…We introduce a novel aspect to the field by investigating the FABP5 gene’s role in mitigating or mediating environmental influences on DA neurochemistry in the striatum, and show that our environment paradigm can influence DA levels in a select region of the brain. The influence of environment on the brain and behavior is in agreement with our previous studies [ 9 , 24 ]. Comparable studies using environment as a factor have targeted other important molecular players involved in the functioning of CB1 receptors, including the main degradative enzymes of endocannabinoids AEA and 2-AG, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), respectively [ 51 ].…”

“…Future studies of the FABP5 gene and DA neurochemistry should include other methods of FABP5 manipulation, such as pharmacological inhibition or selective up/down-regulation using a viral vector. Finally, while our current experimental paradigm has been previously used to compare environmental influence on neurochemistry and behavior [ 9 , 24 ], future studies should include an additional experimental condition of group-housed animals under standard housing conditions to support the present findings.…”

“…In summary, given that there are noted neurochemical changes reported in the present study as well as behavioral differences in FABP5-deficient mice in related cognitive/addiction disease-modeling studies [ 1 , 4 – 6 , 9 , 72 ], and there is an existing modulatory relationship between endocannabinoid signaling and DA content within the midbrain [ 3 , 58 ], further research is needed to investigate FABP5’s neuropathophysiological role in shaping DA circuits.…”

Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise

“…Furthermore, a negative correlation between FABP3 and the Mini-Mental State Examination (MMSE) has also been recently demonstrated in the early stages of AD, underlining that FABP3 could be an early predictor of cognitive decline [ 87 ]. Similarly, FABP5 suppression in mice has been associated with memory impairment and cognitive decline [ 89 ]. In particular, FABP5 seems to affect learning and memory by activating PPARγ signaling pathways.…”

Deciphering Complex Interactions in Bioactive Lipid Signaling

“…Besides enzymes, protein carriers [ 50 ] or microvesicles [ 51 ] that transport bioactive lipids inside and outside the cell can also be expected to contribute to fueling one metabolic route rather than another, as it is becoming apparent in the case of ECBs [ 52 , 53 , 54 ]. Unfortunately, for known lipid transporters such as heat shock protein 70 and albumin [ 55 ], fatty acid-binding proteins 1, 5 and 7 [ 56 , 57 ], FAAH-like anandamide transporter [ 58 ], sterol carrier protein 2 [ 59 ] and retinol-binding protein 2 [ 60 ], the mechanisms that support the choice of one substrate over another also remain to be elucidated.…”