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Nitric oxide (NO) is a fascinating signalling molecule implicated in a plethora of biological functions, especially at the synaptic level. Exploring neurotransmission in the hippocampus could be instrumental in the individuation of putative targets for nitric-oxide mediated neuromodulation, especially in terms of the potential repercussions on fundamental processes i.e. synaptic plasticity and excitability-related phenomena. Among these targets, endovanilloid signalling constitutes an object of study since Transient Receptors Vanilloid type 1 (TRPV1) channels possess a NO-sensitive gate modulating its activation. Also, NO has been referred to as a mediator for numerous endocannabinoid effects. Notwithstanding, the linkage between TRPV1 and NO systems in neuromodulation still remains elusive. To this end, we aim at investigating the involvement of TRPV1 in nitric oxide-mediated influence on hippocampal processes. Electrophysiological whole-cell recordings in CA1 pyramidal neurons were applied to evaluate excitatory neurotransmission in rat brain slices. Indeed, miniature excitatory postsynaptic currents (mEPSCs) were analysed upon pharmacological manipulation of TRPV1 and NO signalling pathways. In detail, only the administration of the specific TRPV1 exogenous agonist – capsaicin - reduced the frequency and amplitude of mEPSC similarly to the inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitroindazole (7NI). In contrast, capsazepine, TRPV1 antagonist, does not influence excitatory transmission. The combined TRPV1 activation and nNOS blockade confirm the presence of a putative common mechanism. When we administered the endovanilloid-endocannabinoid ligand, i.e. anandamide, we unveiled a potentiation of neurotransmission that was selectively reverted by 7NI. Our data suggest that nitric oxide influences TRPV1 hippocampal signalling since these channels are not constitutively active, but can be "on-demand" activated to modulate excitation in CA1 pyramidal neurons, and that this effect is linked to nitric oxide production. [Display omitted] • Nitric oxide production modulates excitatory transmission in CA1 pyramidal neurons. • TRPV1 influence nitrergic modulation of miniature excitatory post-synaptic currents. • Nitrergic intracellular levels are correlated with on-demand TRPV1-CB1 signaling. [ABSTRACT FROM AUTHOR]

[Display omitted] • The composition of Golden Tomato (GT) juice was characterized in terms of phytonutrients. • GT juice modulates brain impairment induced by Metabolic Syndrome (MetS). • GT juice restores anxiety-like behaviour, reactivity and declarative memory in MetS. • GT juice reduces MAPK-ERK and re-establishes PI3K/Akt signalling in specific brain areas. "Golden" tomato (GT) plays a protective role in metabolic dysfunction induced by High-Fat Diet (HFD). Our aim is to characterize the phytonutrient composition of the juice and explore the influence of GT, orally administered for one month, on cognitive impairment associated with Metabolic Syndrome (MetS) in male rats. We investigated reactivity, stress response and memory, together with brain neurotrophic/inflammatory signaling. Our data showed that HFD-induced functional modifications were ameliorated by GT nutritional supplementation. In particular, the behavioural reactivity improved in HFD/GT rats, that also showed a better performance in tests measuring anxiety and anhedonia. Furthermore, GT consumption rescued the declarative memory impairment. Lastly, GT supplementation counteracted HFD-induced brain alterations in PI3K\Akt and MAPK/ERK signalling pathways. In conclusion, this study provides evidence of the importance of food supplementation with GT in the protection from neuroinflammation and cognitive alterations associated with MetS. [ABSTRACT FROM AUTHOR]

Highlights: [•] Early environmental experience and behavioral reactivity in female rats. [•] Early handling manipulation interferes positively with the acquisition of declarative memory. [•] A brief early manipulation induces an improvement in reference and working memory. [•] Early handling increases maternal care thus ameliorating behavioral flexibility and cognitive performance. [ABSTRACT FROM AUTHOR]