Biology subjects

Romcy-Pereira, R. N.

Publications and source records attributed to Romcy-Pereira, R. N..

3 recordsLinked to original sources

bioRxiv2025

Developmental Dysregulation of Synaptic and Myelin-Related Genes in Frontal Cortex and Serum Infrared Spectroscopy Signature in the Valproic Acid Model of Autism

Neural circuits emerge during development through dynamic interactions between genetic instructions and environmental cues that shape cell fate, connectivity, and the timing of myelination. In developmental disorders such as autism, abnormalities in sensory processing, social cognition, and motor behavior are thought to arise from disruptions in these processes. Here, we investigated early-life molecular changes following prenatal exposure to valproic acid (VPA), an environmentally induced model of autism. We integrated cortical gene expression analysis using RNA sequencing/qPCR, alternative splicing profiling, in situ myelin quantification, plasma serotonin determination, and machine learning-assisted classification of blood serum molecular profiles using infrared spectroscopic (FTIR) data. Our findings revealed downregulation of myelin-associated genes and upregulation of synapse-related genes in the frontal cortex of young VPA-exposed rats. qPCR confirmed reduced cortical expression of Mobp and PLP1 along with increased Penk and C1ql3 expression. Alternative splicing analysis identified numerous novel transcript variants, enriched in synaptic-related genes, indicating widespread post-transcriptional remodeling in VPA animals. These molecular alterations were accompanied by a significant reduction in myelin content within the cingulate and motor cortex of adult animals. Peripheral molecular profiling showed elevated plasma serotonin in VPA-treated animals and demonstrated that a support vector machine trained on serum FTIR spectra classified VPA-exposed animals with 85% accuracy. Collectively, our findings suggest that prenatal VPA exposure induces early dysregulation of myelin organization, synaptic gene networks, and RNA splicing programs, potentially leading to long-term impairments in neuronal communication and processing efficiency. Furthermore, our results highlight serum spectroscopic signatures as promising peripheral biomarkers for autism, warranting further investigation.

neuroscience↗

bioRxiv2025

Altered Stress and Fear Responses in the VPA Rat Model of Autism: Behavioral Dissociation Across Tactile, Nociceptive, and Social Contexts

Sensitivity to environmental stimuli is a fundamental aspect of human behavior, and its dysregulation is associated with stress-related and anxiety disorders. In autism spectrum disorder (ASD), altered sensory processing may contribute to increased vulnerability to such conditions. To better understand this relationship, we evaluated autonomic and behavioral responses to tactile, nociceptive, and social stressors in juvenile Wistar rats prenatally exposed to valproic acid (VPA), a widely used animal model of ASD. VPA- treated and saline-treated control (CTL) rats underwent a battery of stress-related behavioral tests. Defecation, freezing and vocalization behaviors were analyzed in response to handling, electro-tactile stimulation, nociceptive foot shock (fear conditioning) and social stress stimuli (emotional contagion). VPA-treated rats maintained increased defecation during handling and a higher prevalence of defecation during electro-tactile stimulation, without corresponding changes in freezing. During fear conditioning, these animals showed delayed onset and heightened freezing responses. Furthermore, unlike CTL rats, VPA-treated rats lacked correlations among freezing, defecation, and vocalization. In the emotional contagion paradigm, observation of shock in the partner increased the prevalence of animals freezing and reduced the prevalence of animals vocalizing in both VPA and CTL groups (oV+ and oC+) compared to their respective controls (oV- and oC-). However, these effects were more sustained in oV+ rats, which also exhibited prolonged freezing behavior and an earlier reduction in vocalization rate. These findings indicate that VPA-treated rats display heightened stress reactivity, habituation deficit and disrupted coordination of fear responses, supporting the VPA model as a relevant tool for investigating the neurobiological basis of stress vulnerability and social dysfunction in ASD.

neuroscience↗

bioRxiv2019

Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

neuroscience↗