BDNF as a Putative Target for Standardized Extract of Ginkgo biloba-Induced Persistence of Object Recognition Memory.

Despite considerable progress on the study of the effect of standardized extract of Gingko biloba (EGb) on memory processes, our understanding of its role in the persistence of long-term memory (LTM) and the molecular mechanism underlying its effect, particularly episodic-like memory, is limited. We here investigated the effects of EGb on the long-term retention of recognition memory and its persistence and BDNF expression levels in the dorsal hippocampal formation (DHF). Adult male Wistar rats (n = 10/group) were handled for 10 min/5 day. On day 6, the animals were treated with vehicle or 0.4 mg/kg diazepam (control groups) or with EGb (250, 500 or 100 mg/kg) 30 min before the training session (TR1), in which the animals were exposed to two sample objects. On day 7, all rats underwent a second training session (TR2) as described in the TR1 but without drug treatment. Object recognition memory (ORM) was evaluated on day 8 (retention test, T1) and day 9 (persistence test, T2). At the end of T1or T2, animals were decapitated, and DHF samples were frozen at -80 °C for analyses of the differential expression of BDNF by Western blotting. EGb-treated groups spent more time exploring the novel object in T2 and showed the highest recognition index (RI) values during the T1 and T2, which was associated with upregulation of BDNF expression in the DHF in a dose-and session-dependent manner. Our data reveal, for the first time, that EGb treatment before acquisition of ORM promotes persistence of LTM by BDNF differential expression.

Nível socioeconômico, saúde bucal e fatores associados no suporte social de gestantes: estudo transversal / Socioeconomic level, oral health, and associated factors in the social support of pregnant women: a cross-sectional study

Avaliar a associação entre variáveis socioeconômicas e relacionadas a saúde bucal no suporte social percebido por gestantes. Esse estudo transversal incluiu uma amostra obtida em conglomerados de gestantes atendidas no serviço público de saúde no sul do Brasil. As gestantes responderam questionários acerca de características demográficas, socioeconômicas e relacionadas à saúde bucal. O suporte social foi avaliado através da escala Medical Outcomes Study. As variáveis clínicas incluíram cárie dentária não tratada e sangramento gengival. Análise de Regressão de Poisson em multinível foram utilizados para avaliar a influência dos preditores no suporte social. A amostra foi composta por254 gestantes. Gestantes com pior autopercepção de saúde bucal, níveis extensivos de sangramento gengival e com menor nível socioeconômico apresentaram um pior suporte social. Fatores socioeconômicos e relacionados à saúde bucal exerceram impacto no suporte social percebido por gestantes.

To evaluate the association between socioeconomic and oral health-related variables in the social support perceived by pregnant women. This cross-sectional study included a sample obtained from clusters of pregnant women who attended public health services in southern Brazil. The pregnant women answered questionnaires about demographic, socioeconomic, and oral health characteristics. Social support was assessed using the Medical Outcomes Study scale. Clinical variables included untreated dental caries and gingival bleeding. Multilevel Poisson regression analysis was used to assess the influence of predictors on social support. The sample consisted of 254 pregnant women. Those with poorer self-perceived oral health, extensive levels of gingival bleeding, and lower socioeconomic status, presented poor social support. Socioeconomic factors and factors related to oral health had an impact on the social support perceived by pregnant women.

Ginkgo biloba treatments reverse the impairment of conditioned suppression acquisition induced by GluN2B-NMDA and 5-HT1A receptor blockade: Modulatory effects of the circuitry of the dorsal hippocampal formation.

To improve our understanding of the effects of standardized extract of Ginkgo biloba (EGb) as a cognitive enhancer, we investigated the conditioned lick suppression-induced expression (mRNA and protein) of the GluN2B-containing N-methyl-D-aspartic acid receptor (GluN2B-NMDAR), serotonin (5-HT) 1A receptor (5-HT1AR), gamma-aminobutyric acid type A receptor (GABAAR) and glial fibrillary acidic protein (GFAP) in the dorsal hippocampal formation (dHF) of untreated and EGb-treated (0.25, 0.5 and 1.0 g.kg-1) groups of rats. To substantiate our data, we analysed the molecular changes in dHF following treatment with vehicle, with agonists or antagonists of GABAAR, GluN2B-NMDAR and 5-HT1AR or with one of these antagonists prior to EGb and fear memory acquisition. Additionally, we performed a pharmacological analysis of the drug-receptor-receptor interactions and their supplemental role in fear memory by blocking individual receptors and analysed the possible changes in expression level with each of the other receptors in the study as well as astrocytes. Our data show for the first time that EGb treatment not only upregulated GluN2B, GABAAR-α5, and GFAP compared with the control but also differentially upregulated GABAAR-α1 in the dHF and 5HT1AR in the CA3. We found that the activation of GABAARs (diazepam) and the inactivation of GluN2B-NMDARs (Ro25-6981) or 5-HT1AR ((S)-WAY100135) resulted in memory impairment. Further, higher doses of EGb treatment reversed the effect of blocking GluN2B (P < 0.001) and 5-HT1AR (P < 0.001). Here, treatment with Ro25-6981 + EGb or (S)-WAY100135 + EGb prevented the impairment of the acquisition of lick suppression in association with the upregulation or prevention of the downregulation of Grin2b expression as well as the expression of GluN2B-NMDA and/or α1 and α5 subunit-containing GABAAR in the CA1 (P < 0.0001). Our data are in line with previous findings concerning the necessity of GluN2B for fear memory formation and add to the current knowledge of the role of the GABAAR-α1 and -α5 subunits and of GluN2B as a target of cognitive enhancers. Furthermore, our data show that these receptors play a complementary role in controlling the neural circuitry in the dHF that seems to be essential to conditioned lick suppression and the modulatory effects of EGb.

Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches.

The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission; the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT1ARs), and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1AR, GABAARs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABAARs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htr1a, Grin2a, Gabra5, and Erk2 after the retention test and of Htr1a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT1ARs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htr1a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments.

Flavones from Erythrina falcata are modulators of fear memory.

BACKGROUND: Flavonoids, which have been identified in a variety of plants, have been demonstrated to elicit beneficial effects on memory. Some studies have reported that flavonoids derived from Erythrina plants can provide such beneficial effects on memory. The aim of this study was to identify the flavonoids present in the stem bark crude extract of Erythrina falcata (CE) and to perform a bioactivity-guided study on conditioned fear memory. METHODS: The secondary metabolites of CE were identified by high performance liquid chromatography combined with a diode array detector, electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSn) and nuclear magnetic resonance (NMR). The buthanolic fraction (BuF) was obtained by partitioning. Subfractions from BuF (BuF1 - BuF6) and fraction flavonoidic (FfA and FfB) were obtained by flash chromatography. The BuF3 and BuF4 fractions were used for the isolation of flavonoids, which was performed using HPLC-PAD. The isolated substances were quantified by HPLC-DAD and their structures were confirmed by nuclear magnetic resonance (NMR). The activities of CE and the subfractions were monitored using a one-trial, step-down inhibitory avoidance (IA) task to identify the effects of these substances on the acquisition and extinction of conditioned fear in rats. RESULTS: Six subclasses of flavonoids were identified for the first time in CE. According to our behavioral data, CE, BuF, BuF3 and BuF4, the flavonoidic fractions, vitexin, isovitexin and 6-C-glycoside-diosmetin improved the acquisition of fear memory. Rats treated with BuF, BuF3 and BuF4 were particularly resistant to extinction. Nevertheless, rats treated with FfA and FfB, vitexin, isovitexin and 6-C-glycoside-diosmetin exhibited gradual reduction in conditioned fear response during the extinction retest session, which was measured at 48 to 480 h after conditioning. CONCLUSIONS: Our results demonstrate that vitexin, isovitexin and diosmetin-6-C-glucoside and flavonoidic fractions resulted in a significant retention of fear memory but did not prevent the extinction of fear memory. These results further substantiate that the treatment with pure flavonoids or flavanoid-rich fractions might represent potential therapeutic approaches for the treatment of neurocognitive disorders, improvement of memory acquisition and spontaneous recovery of fear.