Biology subjects

Alves, R. L.

Publications and source records attributed to Alves, R. L..

3 recordsLinked to original sources

bioRxiv2021

Altered environmental perception by parental stress and depression vulnerability: impact on mothers and offspring

Depressive 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 separation-MS) 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.

neuroscience↗

bioRxiv2019

Alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior

Alcohol use adversely impacts the life of millions of people worldwide. Deficits in synaptic transmission and in microglial function are common findings in human alcohol users and in animal models of alcohol intoxication. Here, we show that alcohol intake over ten consecutive days resulted in substantial loss of excitatory synapse in the prefrontal cortex, a consequence of aberrant synaptic pruning, which led to increased anxiety-like behavior. Mechanistically, these effects of alcohol intake were mediated by a detrimental increase of microglia engulfment capacity via Src-dependent activation of NFkB and consequent TNF production. Accordingly, pharmacological blockade of Src activation or TNF production by microglia, genetic ablation of TNF, or diphtheria toxin-mediated conditional ablation of microglia attenuated aberrant synaptic pruning preventing excitatory synapse loss and anxiety-like behavior. Overall, our data suggest that aberrant pruning of excitatory synapses by microglia might disrupt synaptic transmission during alcohol use.

neuroscience↗

bioRxiv2017

Genetic ablation of RhoA in adult microglia causes synapse and neuronal loss

Nervous tissue homeostasis requires 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 LTP, formation of {beta}-amyloid plaques and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated Tnf production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also found that the Rhoa/Src signaling pathway was disrupted in microglia of the APP/PS1 mouse model of Alzheimers disease and that low doses of A{beta} oligomers triggered microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing RhoGTPase signaling in microglia can directly cause neurodegeneration.

neuroscience↗