Search

Memory and GABAergic activity in the hippocampus of stressed rats improve after n-3 polyunsaturated fatty acid (PUFA) supplementation. On the other hand, cannabinoid receptor type 1 (CB1) strongly regulates inhibitory neurotransmission in the hippocampus. Speculation about a possible relation between stress, endocannabinoids, and PUFAs. Here, we examined whether the effects of PUFAs on memory of chronically stressed rats depends on pharmacological manipulation of CB1 receptors. Male Sprague-Dawley rats were orally supplemented with n-3 (fish oil) or n-6 (primrose oil) PUFAs during chronic restraint stress (CRS) protocol (6 h/day; 21 days). First, we studied if the expression of CB1 receptors in the hippocampus may be affected by CRS and PUFAs supplementation by real-time PCR and immunofluorescence. CRS up-regulated the CB1 expression compared with the non-stressed rats, while only n-3 PUFAs countered this effect. Memory was evaluated in the Morris water maze. Stressed rats were co-treated with PUFAs and/or modulators of CB1 receptor (AM251, antagonist, 0.3 mg/kg/day; WIN55,212-2, agonist, 0.5 mg/kg/day) by intraperitoneal injections. Memory improved in the stressed rats that were treated with AM251 and/or n-3 PUFAs. Supplementation with n-6 PUFAs did not affect memory of stressed rats, but co-treatment with AM251 improved it, while co-treatment with WIN55,212-2 did not affect memory. Our results demonstrate that activity of the CB1 receptors may modulate the effects of PUFAs on memory of stressed rats. This study suggests that endocannabinoids and PUFAs can both become a singular system by being self-regulated in limbic areas, so they control the effects of stress on the brain.

In modern lifestyle, stress and Western diets are two major environmental risk factors involved in the etiology of neuropsychiatric disorders. Lifelong interactions between stress, Western diets, and how they can affect brain physiology, remain unknown. A possible relation between dietary long chain polyunsaturated fatty acids (PUFA), endocannabinoids, and stress is proposed. This review suggests that both Western diets and negative stress or distress increase n-6/n-3 PUFA ratio in the phospholipids of the plasma membrane in neurons, allowing an over-activation of the endocannabinoid system in the limbic areas that control emotions. As a consequence, an excitatory/inhibitory imbalance is induced, which may affect the ability to synchronize brain areas involved in the control of stress responses. These alterations increase vulnerability to neuropsychiatric disorders. Accordingly, dietary intake of n-3 PUFA would counter the effects of stress on the brain of stressed subjects. In conclusion, this article proposes that PUFA, endocannabinoids, and stress form a unique system which is self-regulated in limbic areas which in turn controls the effects of stress on the brain throughout a lifetime.

Organophosphate pesticides have been classically described as inhibitors of acetylcholinesterase (AChE) activity in insects and invertebrates. However, there is now more evidence supporting the hypothesis that these compounds also act through noncholinergic pathways, especially those related to cognitive processes. The enzyme acylpeptide hydrolase was identified as a new target for organophosphate pesticides. This enzyme is more sensitive than AChE to some organophosphates (OP), including dichlorvos, which is the parent compound for metrifonate, a therapeutic agent used in the treatment of cognitive impairment associated to Alzheimer's disease. Therefore, there is some doubt as to whether the mechanism of action of this drug is mediated by a potentiation of cholinergic transmission. However, the direct action of acylpeptide hydrolase in cognitive processes and the physiological and molecular mechanisms underlying subacute exposure to OP have yet to be demonstrated. This review deals with evidence demonstrating the existence of mechanisms of actions of OP, which are independent of cholinergic pathway potentiation and which have an effect on cognitive processes. In addition, the possible participation of the enzyme acylpeptide hydrolase in these processes is also discussed. Finally, the possibility of using this enzyme activity as a new biomarker for exposure to OP is considered.