Browsing by Author "Alves, Renata L."
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- Altered environmental perception by parental stress and depression vulnerability: impact on mothers and offspringPublication . Alves, Renata L.; Portugal, Camila C.; Lopes, Igor M.; Oliveira, Pedro; Alves, Cecília J.; Barbosa, Fernando; Summavielle, Teresa; Magalhães, Ana; Summavielle, TeresaDepressive mothers often find the mother-child interaction to be challenging. Parental stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depression (Wistar and Kyoto) to investigate the impact of stress (maternal separationMS) on maternal behaviour and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behaviour after weaning, while worsening their adolescent offspring cognitive behaviour. Whereas MS in Wistar dams elicited higher quality of pup-directed behaviour, increasing Brain-Derived Neurotrophic Factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to impact the salience of the social environment cues (as negative for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behaviour and stress regulatory processes.
- Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerabilityPublication . Alves, Renata L.; Oliveira, Pedro; Lopes, Igor M.; Portugal, Camila C.; Alves, Cecília J.; Barbosa, Fernando; Summavielle, Teresa; Magalhães, AnaThe development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor.
- Maternal separation effects on mother rodents’ behaviour: A systematic reviewPublication . Alves, Renata L.; Portugal, Camila Cabral; Summavielle, Teresa; Barbosa, Fernando; Magalhães, AnaMaternal separation (MS) is a widely-used paradigm to study the effect of early-life adversity on brain development and resilience to psychopathology. Most of the related literature focuses on MS impact on offspring, however, it should ideally also consider the impact of altered maternal behaviour caused by MS itself. This systematic review aimed at providing a comprehensive compilation of the effects of MS on key maternal behaviour aspects. We performed a keyword literature search using Boolean operators. Databases were searched between 2000-2018. Additional studies were included from manual search. Twenty-nine articles addressing the impact of MS on maternal behaviour and/or mothers’ anxiety, depression-like behaviour, memory and consequences on underlying mechanisms. The methodological aspects and main conclusions were extracted from each study. This review shows that MS induces changes in dams. Results are particularly robust for increased anxiety and depressive-like symptoms, and altered maternal behaviours, predominantly for longer periods of MS. Finally, research in the field could strongly benefit from the establishment of guidelines to reduce the methodological inconsistencies here identified.
- Maternal stress and vulnerability to depression: coping and maternal care strategies and its consequences on adolescent offspringPublication . Alves, Renata L.; Portugal, Camila C.; Lopes, Igor M.; Oliveira, Pedro; Alves, Cecília J.; Barbosa, Fernando; Summavielle, Teresa; Magalhães, AnaDepressive mothers often find mother-child interaction to be challenging. Maternal stress may further impair mother-child attachment, which may increase the risk of negative developmental consequences. We used rats with different vulnerability to depressive-like behavior (Wistar and Kyoto) to investigate the impact of stress (maternal separation-MS) on maternal behavior and adolescent offspring cognition. MS in Kyoto dams increased pup-contact, resulting in higher oxytocin levels and lower anxiety-like behavior after weaning, while worsening their adolescent offspring cognitive behavior. Whereas MS in Wistar dams elicited higher quality of pup-directed behavior, increasing brain-derived neurotrophic factor (BDNF) in the offspring, which seems to have prevented a negative impact on cognition. Hypothalamic oxytocin seems to affect the salience of the social environment cues (negatively for Kyoto) leading to different coping strategies. Our findings highlight the importance of contextual and individual factors in the understanding of the oxytocin role in modulating maternal behavior and stress regulatory processes.
- Microglia dysfunction caused by the loss of rhoa disrupts neuronal physiology and leads to neurodegenerationPublication . Socodato, Renato; Portugal, Camila C.; Canedo, Teresa; Rodrigues, Artur; Almeida, Tiago O.; Henriques, Joana F.; Vaz, Sandra H.; Magalhães, João; Silva, Cátia M.; Baptista, Filipa I.; Alves, Renata L.; Coelho-Santos, Vanessa; Silva, Ana Paula; Paes-de-Carvalho, Roberto; Magalhães, Ana; Brakebusch, Cord; Sebastião, Ana M.; Summavielle, Teresa; Ambrósio, António F.; Relvas, João B.Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of β-amyloid plaques, and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated tumor necrosis factor (TNF) production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also find that the Rhoa/Src signaling pathway is disrupted in microglia of the APP/PS1 mouse model of Alzheimer disease and that low doses of Aβ oligomers trigger microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing Rho GTPase signaling in microglia can directly cause neurodegeneration.