Browsing by Author "Summavielle, Teresa"
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- 3D vs 2D Cell Cultures in the Evaluation of Radiobiological Effects of Exposition to Low Doses - Medical Imaging Levels - of Ionizing RadiationPublication . Costa, Pedro; Caires, Hugo; Lemos, Joana; Cunha, Lídia; Bravo, Joana; Bravo, Isabel; Silva, Regina; Summavielle, Teresa; Metello, Luís F.Pretending to develop advanced biological models to study biological effects of low doses of ionizing radiation and following the actual policies on Animal Sciences, based on 3 R’s Rule (to Reduce, Refine and Replace) – that limits as much as possible the application of animal models – scientific research using cellular models is constantly increasing. Nevertheless, the intrinsic limitations of actual cellular models quite often had been recognized on a significant number of papers pointing a significant number of non-concordances between results obtained using in vitro and in vivo studies. Actually, an increasing number of authors admit that three-dimensional cell culture (and spheroid cell culture in particular) could represent an interesting solution and a step further on use of cellular models. The work here to be presented reflects the first phase on the use of this methodology on the study, evaluation and quantification of cellular effects of low doses – starting on medical imaging level - of exposition to ionizing radiation.
- Abnormal immunoreactivity to serotonin in cerebellar purkinje cells after neonatal cocaine exposurePublication . Summavielle, Teresa; Alves, Cecília J.; Monteiro, Pedro; Tavares, Maria AméliaNeonatal cocaine is known to affect the developing serotonergic system in many brain structures, including the cerebellum. Changes in the cerebellar Purkinje cells after drug exposure are well documented and result in impairment of movement and other cerebellar disorders such as ataxia. These cells have a major postnatal developmental pattern; therefore, neonatal exposure to cocaine is likely to affect them. In this work, male and female Wistar rats were injected with 15 mg of cocaine hydrochloride/kg body weight/day, subcutaneously, in two daily doses, from postnatal day 1 (PND1) to PND29. Controls were given 0.9% of saline. On PND14, PND21, and PND30, rats were transcardially perfused, and brains removed and cryoprotected. Coronal sections from the cerebellum were processed for immunocytochemistry of cells containing serotonin (5-hydroxytryptamine, or 5-HT). At the same postnatal age, rats from at least three different litters were sacrificed by decapitation, and brains were dissected for determination of 5-HT in the cerebellum by high-performance liquid chromatography with electrochemical detection. Upon the expected distribution of immunoreactivity to 5-HT, an abnormal immunoreactivity to 5-HT was observed in the Purkinje cells of six cocaineexposed animals, but not in control animals. Also, levels of cerebellar 5-HT in cocaine-exposed rats were significantly increased on PND21. These results, together with previously reported observations of altered patterns of motor behavior, indicate that neonatal cocaine exposure affects the serotonergic cerebellar system, altering the standard development of Purkinje cells and possibly compromising the motor function.
- Acetil-L-Carnitina como neuroprotetor na excitotoxicidade do glutamatoPublication . Casais, Joana; Lobo, Andrea; Summavielle, TeresaA excitotoxicidade consiste na ativação excessiva de recetores de glutamato, causada pela acumulação extracelular deste neurotransmissor. A ativação dos recetores de glutamato promove o aumento excessivo da concentração intracelular de cálcio e morte neuronal associada à ativação de protéases como calpaínas e caspases - acontecimentos típicos de patologias como isquémia cerebral, Alzheimer, Parkinson e Huntington. A acetil-L-carnitina (ALC) é um éster da L-carnitina com funções neuroprotetoras, mas o mecanismo envolvido permanece desconhecido.
- Acetyl-L-Carnitine Improves Cell BioenergeticsPublication . Cunha, Lídia; Bravo, Joana; Costa, Pedro; Fernandes, Sílvia; Oliveira, Marta; Castro, Rosa; Metello, Luís F.; Summavielle, TeresaIntroduction: Acetyl-L-Carnitine (ALC), a natural occurring compound in all mammalian species, plays a variety of vital functions in the body. The most important are related to mitochondria, namely the transport of fatty acids for energy production through β oxidation and the control of acyl-CoA/CoA ratio. Due to this close interaction with cell bioenergetics, it plays a role in many diseases, especially those related to the mitochondria. We propose to characterize the action of ALC in mitochondrial bioenergetics and functional integrity.
- Acetyl-L-Carnitine prevents methamphetamine-induced structural damage on endothelial cells via ILK-related MMP-9 activityPublication . Summavielle, Teresa; Fernandes, S.; Salta, S.; Bravo, J.; Silva, A.P.Methamphetamine (METH) is a potent psychostimulant highly used worldwide. Recent studies evidenced the involvement of METH in the breakdown of the blood-brain-barrier (BBB) integrity leading to compromised function. The involvement of the matrix metalloproteinases (MMPs) in the degradation of the neurovascular matrix components and tight junctions (TJs) is one of the most recent findings in METH-induced toxicity. As BBB dysfunction is a pathological feature of many neurological conditions, unveiling new protective agents in this field is of major relevance. Acetyl- L-carnitine (ALC) has been described to protect the BBB function in different paradigms, but the mechanisms underlying its action remain mostly unknown. Here, the immortalized bEnd.3 cell line was used to evaluate the neuroprotective features of ALC in METH-induced damage. Cells were exposed to ranging concentrations of METH, and the protective effect of ALC 1 mM was assessed 24 h after treatment. F-actin rearrangement, TJ expression and distribution, and MMPs activity were evaluated. Integrin-linked kinase (ILK) knockdown cells were used to assess role of ALC in ILK mediated METH-triggered MMPs’ activity. Our results show that METH led to disruption of the actin filaments concomitant with claudin-5 translocation to the cytoplasm. These events were mediated by MMP-9 activation in association with ILK overexpression. Pretreatment with ALC prevented METH-induced activation of MMP-9, preserving claudin-5 location and the structural arrangement of the actin filaments. The present results support the potential of ALC in preserving BBB integrity, highlighting ILK as a new target for the ALC therapeutic use.
- ALC Neuroprotection through autophagy and ups acitivityPublication . Bravo, Joana; Cunha, Lídia; Fernandes, Sílvia; Binienda, Zbigniew; Summavielle, TeresaAcetyl–L-carnitine (ALC) has beneficial effects in neurodegenerative diseases and was shown to be protective against exposure to methamphetamine (METH) reducing mitochondrial dysfunction and oxidative stress. However, the mechanisms underlying ALC action are still unknown, limiting its putative therapeutic use.
- 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.
- Antipsychotic therapy and biochemical laboratory profile characterization of a sample of patients diagnosed with schizophreniaPublication . Amorim, Manuela; Moreira, A.; Condeço, Jorge; Monteiro, Pedro; Marques, António; Summavielle, TeresaSchizophrenia (SCZ) patients are reported to present significant abnormalities in lipid and glucose metabolism, that increase the risk for cardiovascular disease and diabetes, possibly induced by antipsychotic therapy (APT) and lifestyle.
- Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetaminePublication . Canedo, Teresa; Portugal, Camila Cabral; Socodato, Renato; Almeida, Tiago Oliveira; Terceiro, Ana Filipa; Bravo, Joana; Silva, Ana Isabel; Magalhães, João Duarte; Guerra-Gomes, Sónia; Oliveira, João Filipe; Sousa, Nuno; Magalhães, Ana; Relvas, João Bettencourt; Summavielle, TeresaMethamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
- Bone injury and repair trigger central and peripheral NPY Neuronal PathwaysPublication . Alves, Cecília J.; Alencastre, Inês S.; Neto, Estrela; Ribas, João; Ferreira, Sofia; Vasconcelos, Daniel M.; Sousa, Daniela M.; Summavielle, Teresa; Lamghari, MeriemBone repair is a specialized type of wound repair controlled by complex multi-factorial events. The nervous system is recognized as one of the key regulators of bone mass, thereby suggesting a role for neuronal pathways in bone homeostasis. However, in the context of bone injury and repair, little is known on the interplay between the nervous system and bone. Here, we addressed the neuropeptide Y (NPY) neuronal arm during the initial stages of bone repair encompassing the inflammatory response and ossification phases in femoral-defect mouse model. Spatial and temporal analysis of transcriptional and protein levels of NPY and its receptors, Y1R and Y2R, reported to be involved in bone homeostasis, was performed in bone, dorsal root ganglia (DRG) and hypothalamus after femoral injury. The results showed that NPY system activity is increased in a time- and space-dependent manner during bone repair. Y1R expression was trigged in both bone and DRG throughout the inflammatory phase, while a Y2R response was restricted to the hypothalamus and at a later stage, during the ossification step. Our results provide new insights into the involvement of NPY neuronal pathways in bone repair.