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Studies on maternal microRNA expression have emerged to better understand regulatory mechanisms during the gestational period, since microRNA expression has been associated with pregnancy disorders.This study aims to investigate the association between the expression of the maternal microRNAs miR-let-7d-3p and miR-451a during the second gestational trimester and neuropsychomotor development at 90 days of life of infants.This is a case-control study nested within a cohort, with the groups being divided into dyads in which pregnant women presented Major Depressive Episode (MDE) (n = 64), these being the cases, and their respective controls (no MDE; n = 64). The Bayley Scale III was used to assess the outcome of child development, and MDE was assessed through the Mini International Neuropsychiatric Interview Plus. The analysis of miR-let-7d-3p and miR-451a was done via serum from the pregnant women, utilizing the qRT-PCR (n = 128).The results indicated a negative association between expression levels of miR-451a (β -3.3 CI95% -6.4;-0.3) and a positive associated of the miR-let-7d-3p with the cognitive development domain (β 1.7 CI95% 0.1; 3.0), and a positive association between expression of miR-let-7d-3p with motor development of the infants (β 1.6 CI95% 0.3; 2.9).This is a pioneering study on the topic that indicates a biological interrelationship between the miRNAs miR-let-7d-3p and miR-451a evaluated during the pregnancy and the motor and cognitive domains of infant development at 90 days postpartum.

Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.

Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Methylphenidate (MPH) is the preferred treatment used for attention-deficit/hyperactivity disorder (ADHD). Recently, misuse for MPH due to its apparent cognitive enhancer properties has been reported. Adenosine is a neuromodulator known to exert influence on the dopaminergic neurotransmission, which is the main pharmacological target of MPH. We have reported that an overdosage of MPH up-regulates adenosine A1 receptors in the frontal cortex, but this receptor was not involved in its anxiolytic effects. In this study, the role of adenosine A1 receptor was investigated on MPH-induced effects on aversive and recognition memory in adult mice. Adult mice received acute and chronic (15 days) administration of methylphenidate (5 mg/kg, i.p.), or an acute overdosage (50 mg/kg, i.p) in order to model misuse. Memory was assessed in the inhibitory avoidance and object recognition task. Acute administration 5 mg/kg improved whereas 50 mg/kg disrupted recognition memory and decreased performance in the inhibitory avoidance task. Chronic administration did not cause any effect on memory, but decreased adenosine A1 receptors immunocontent in the frontal cortex. The selective adenosine A1 receptor antagonist, (DPCPX 1 mg/kg, i.p.), prevented methylphenidate-triggered recognition memory impairment. Our findings showed that recognition memory rather than aversive memory was differently affected by acute administration at both doses. Memory recognition was fully impaired by the overdosage, suggesting that misuse can be harmful for cognitive functions. The adenosinergic system via A1 receptors may play a role in the methylphenidate actions probably by interfering with dopamine-enhancing properties of this drug.

Environmental enrichment (EE) is an experimental model for studying neuroplasticity. EE is used to investigate behavioral modifications associated with gene-environmental interaction. The object recognition task (ORT) evaluates animals' ability to learn about their environment, which depends on their innate instinct. By using young CF1 mice, the present study evaluated the effect of 8 weeks of EE on the ORT. Our results indicate that EE decreased the time the animals spent exploring familiar and unfamiliar objects and total time spent exploring both objects, without affecting the capacity of discrimination of objects. These findings indicate a more propitious behavior for species survival in animals subjected to EE, including rapid exploration and learning about the environment.

Caffeine is one of the most psychostimulants consumed all over the world that usually presents positive effects on cognition. In this study, effects of caffeine on mice performance in the object recognition task were tested in different intertrial intervals. In addition, it was analyzed the effects of caffeine on brain derived neurotrophic factor (BDNF) and its receptor, TrkB, immunocontent to try to establish a connection between the behavioral finding and BDNF, one of the neurotrophins strictly involved in memory and learning process. CF1 mice were treated during 4 consecutive days with saline (0.9 g%, i.p.) or caffeine (10 mg/kg, i.p., equivalent dose corresponding to 2–3 cups of coffee). Caffeine treatment was interrupted 24 h before the object recognition task analysis. In the test session performed 15 min after training session, caffeine-treated mice recognized more efficiently both the familiar and the novel object. In the test session performed 90 min and 24 h after training session, caffeine did not change the time spent in the familiar object but increased the object recognition index, when compared to control group. Western blotting analysis of hippocampus from caffeine-treated mice revealed an increase in BDNF and TrkB immunocontent, compared to their saline-matched controls. Phospho-CREB immunocontent did not change with caffeine treatment. Our results suggest that acute treatment with caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus.

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, delta-aminolevulic acid dehydratase (delta-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe)(2), was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of delta-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe)(2) (0.5mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of delta-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe)(2) protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.