Resveratrol Regulates BDNF, trkB, PSA-NCAM, and Arc Expression in the Rat Cerebral Cortex after Bilateral Common Carotid Artery Occlusion and Reperfusion

Abstract

The polyphenol resveratrol (RVT) may drive protective mechanisms of cerebral homeostasis during the hypoperfusion/reperfusion triggered by the transient bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R). This immunochemical study investigates if a single dose of RVT modulates the plasticity-related markers brain-derived neurotrophic factor (BDNF), the tyrosine kinase trkB receptor, Polysialylated-Neural Cell Adhesion Molecule (PSA-NCAM), and Activity-regulated cytoskeleton-associated (Arc) protein in the brain cortex after BCCAO/R. Frontal and temporal-occipital cortical regions were examined in male Wistar rats randomly subdivided in two groups, sham-operated and submitted to BCCAO/R. Six hours prior to surgery, half the rats were gavage fed a dose of RVT (180 mg·kg−1 in 300 µL of sunflower oil as the vehicle), while the second half was given the vehicle alone. In the frontal cortex of BCCAO/R vehicle-treated rats, BDNF and PSA-NCAM decreased, while trkB increased. RVT pre-treatment elicited an increment of all examined markers in both sham- and BCCAO/R rats. No variations occurred in the temporal-occipital cortex. The results highlight a role for RVT in modulating neuronal plasticity through the BDNF-trkB system and upregulation of PSA-NCAM and Arc, which may provide both trophic and structural local support in the dynamic changes occurring during the BCCAO/R, and further suggest that dietary supplements such as RVT are effective in preserving the tissue potential to engage plasticity-related events and control the functional response to the hypoperfusion/reperfusion challenge.

Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion

“…Assessment of the BDNF densitometric values by a two-way ANOVA ( Table 1 ) revealed an effect of BCP ( p < 0.0001). The slight reduction of BDNF relative levels in the BCCAO/R rats (0.7592 ± 0.01 in sham rats vs. 0.6936 ± 0.004 in BCCAO/R rats) is consistent with previously published data [ 20 ]. Such a decrease was highly statistically significant with an unpaired t -test analysis ( p < 0.0001), however, it did not reach the statistical significance with the pair-wise contrasts run after the ANOVA.…”

“…So far, evidence in this area of research shows that the acute transient bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R) is a model that can mimic in vivo the biological effects of acute cerebral oxidative stress and the early formation of a deleterious pro-inflammatory milieu [ 9 , 10 ]. Indeed, evidence shows that the BCCAO/R affects the brain tissue physiological homeostasis as early as 30 min [ 11 , 12 ] after surgery and appears to directly correlate to molecular marker adaptive changes in brain tissue and plasma [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

“…Emerging evidence reveals that natural products with anti-inflammatory and anti-oxidant properties exert preventive effects against the cerebral molecular dysfunction induced by acute BCCAO/R [ 12 , 15 , 18 , 19 , 20 ]. Among the most promising natural products, the bicyclic sesquiterpene beta-caryophyllene (BCP), a compound that is commonly found in the essential oils of many food plants [ 22 , 23 ], and represents a primary component in the Cannabis sativa L. plant [ 22 ].…”

Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

“…In support of this, several studies have shown that treatment of mice with RSV does result in improvements in memory and cognitive function: Labban et al [ 127 ] saw improvements in a passive avoidance task in an AD mouse model with RSV (male SWR/J mice, 40 mg/kg/day RSV via IP, AlCl 3 induced NFT), Palomera-Avalos et al [ 128 ] showed improvements in novel object recognition (NORT) and open field tests (OFT) in a metabolically impaired model (22 month old C57BL/6J mice, high-fat diet (HFD) 60% calories from fat, 160 mg/kg/day RSV from chow), and Cao et al [ 129 ] (Male/female Sprague–Dawley rats, 100 mg/kg/day RSV from chow) similarly showed RSV-induced cognitive improvements in t -test exploration/success rates as well as improvements in Morris Water Maze (MWM) escape latency. RSV has also been reported to induce increases in early-LTP markers Arc and PSA-NCAM, BDNF [ 130 ], and late-LTP markers synaptophysin, PSD95, PSD93, and CREB in models of cerebral vascular disease [ 131 ], as well as regulate AMPAR expression and NDMA-mediated Ca 2+ influx [ 132 ]. These studies are promising in that they suggest that RSV can improve global cognition in disease states and that at least a portion of RSV’s improvements could come from improved synaptic protein expression, which is likely driven through SIRT1 activation of CREB [ 133 ].…”

“…Many studies report that RSV induces pro-synaptic plasticity effects, be it through changes in LTP-inducing proteins or morphological changes in synaptic structure [ 127 , 129 , 130 , 132 , 133 ]. While it is certainly true that increased synaptic expression of LTP-inducing proteins [ 47 ] and morphological changes [ 60 ] can be directly linked to improvements in cognition, it is important to demonstrate that these changes in expression will result in the increased translocation of key proteins to the synapse, and that this results in improvements in synaptic transmission rates.…”