Navegando por Autor "Brandão, Juliana Alves"

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Epigenetic Inheritance of behavior and organization of cortical circuits in the VPA animal model of autism
(2015-07-11) Brandão, Juliana Alves; Souza, Carolina Araujo; Fernandes, Pedro Bruno; Soares, Ana Maria Araújo; Costa, Marcos Romualdo; Romcy-Pereira, Rodrigo Neves
Autism comprises a heterogeneous group of neuro-developmental disorders that affects brain maturation and produces sensory, motor, language and social interaction deficits with early childhood onset. Many studies indicate that the expression of autistic symptoms is a result of the interaction of predisposing genetic factors and environmental signals during embryonic and early-postnatal life. More recently, studies in animal models have demonstrated that embryonic developmental dysfunctions are at the basis of neuronal and synaptic maturation abnormalities leading to impairments in neural circuit and behavior functions similar to those seen in autism. In the VPA animal model of autism, rats prenatally exposed to valproic acid (VPA) also display behavioral, anatomical and physiological abnormalities reminiscent of autism endophenotypes. However, it is still unknown the degree of behavior and neural connectivity inheritability in this exogenously induced model. Here, we evaluated the behavioral performance and the organization of prefrontal cortex inhibitory circuit in young rats born from parents exposed to VPA and compared them to age-matched VPA-treated and untreated controls. Our results show that rats prenatally exposed to VPA (F1 generation) have a delayed latency for eyeopening during early post-natal development, reduced weight gain from P28 to P35, and clear autistic-like behavioral abnormalities during adolescence, such as hyperlocomotion, prolonged stereotyped behaviors and reduced social interaction when compared to untreated controls. Interestingly, their offspring at the same age (F2 generation - not exposed to VPA) resembled more the F1 generation than the untreated controls. F2 animals showed protracted eye-opening latencies, hyperactivity and a significant social interaction deficit as compared to untreated controls. However, these animals had normal weight gain until P35 and no significant differences in stereotypy parameters - thus suggesting an intermediate phenotype. Analysis of cortical GABAergic interneurons revealed a global decrease in the number of parvalbumin+ cells in the medial prefrontal cortex (mPFC) of F1 animals, in contrast to an increase in F2 animals when compared to untreated controls. In F1, the decrease was mostly due to cell loss in the anterior cingulate cortex, whereas in F2 animals the increase was associated to increased number of cells in all mPFC sub-fields (anterior cingulate cortex, prelimbic area and infralimbic area). The most significant increase in parvalbumin+ cells was seen in the deep cortical layers (V-VI) of F2 animals. Altogether, these findings suggest that an unbalance in prefrontal inhibitory circuits may subserve the locomotor and social behavior deficits observed in rats prenatally exposed to VPA and their offspring. In addition, it shows behavioral and circuit dysfunction inheritance in this animal model of autism.
Evidence of progenitor cell lineage rerouting in the adult mouse hippocampus after status epilepticus
(Frontiers in Neuroscience, 2020-09-18) Moura, Daniela Maria de Sousa; Brandão, Juliana Alves; Lentini, Celia; Heinrich, Christophe; Queiroz, Claudio Marcos Teixeira de; Costa, Marcos Romualdo
Cell lineage in the adult hippocampus comprises multipotent and neuron-committed progenitors. In the present work, we fate-mapped neuronal progenitors using Dcx-CreERT2 and CAG-CAT-EGFP double-transgenic mice (cDCX/EGFP). We show that 3 days after tamoxifen-mediated recombination in cDCX/EGFP adult mice, GFP+ cells in the dentate gyrus (DG) co-expresses DCX and about 6% of these cells are proliferative neuronal progenitors. After 30 days, 20% of GFP+ generated from these progenitors differentiate into GFAP+ astrocytes. Unilateral intrahippocampal administration of the chemoconvulsants kainic acid (KA) or pilocarpine (PL) triggered epileptiform discharges and led to a significant increase in the number of GFP+ cells in both ipsi and contralateral DG. However, while PL favored the differentiation of neurons in both ipsi- and contralateral sides, KA stimulated neurogenesis only in the contralateral side. In the ipsilateral side, KA injection led to an unexpected increase of astrogliogenesis in the Dcx-lineage. We also observed a small number of GFP+/GFAP+ cells displaying radial-glia morphology ipsilaterally 3 days after KA administration, suggesting that some Dcx-progenitors could regress to a multipotent stage. The boosted neurogenesis and astrogliogenesis observed in the Dcx-lineage following chemoconvulsants administration correlated, respectively, with preservation or degeneration of the parvalbuminergic plexus in the DG. Increased inflammatory response, by contrast, was observed both in the DG showing increased neurogenesis or astrogliogenesis. Altogether, our data support the view that cell lineage progression in the adult hippocampus is not unidirectional and could be modulated by local network activity and GABA-mediated signaling
Impaired Processing in the Primary Auditory Cortex of an Animal Model of Autism
(Universidade Federal do Rio Grande do Norte, 2015) Anomal, Renata Figueiredo; Villers-Sidani, Etienne de; Brandão, Juliana Alves; Diniz, Rebecca; Costa, Marcos Romualdo; Romcy-Pereira, Rodrigo Neves
Autism is a neurodevelopmental disorder clinically characterized by deficits in communication, lack of social interaction and repetitive behaviors with restricted interests. A number of studies have reported that sensory perception abnormalities are common in autistic individuals and might contribute to the complex behavioral symptoms of the disorder. In this context, hearing incongruence is particularly prevalent. Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA) during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI) and its local inhibitory circuitry. Our results show that VPA rats have distorted primary auditory maps with over-representation of high frequencies, broadly tuned receptive fields and higher sound intensity thresholds as compared to controls. However, we did not detect differences in the number of parvalbumin-positive interneurons in AI of VPA and control rats. Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons. These data support the notion that fine circuit alterations, rather than gross cellular modification, could lead to neurophysiological changes in the autistic brain

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Navegando por Autor "Brandão, Juliana Alves"