👤 Victoria Romashchenko

This study examines neuroanatomical and molecular changes that may be responsible for cognitive impairment in the BTBR mouse model of autism. Compared to control C57Bl/6 mice, BTBR mice exhibited cognitive inflexibility, impaired in an operant learning task. MRI revealed significant brain abnormalities, including reduced cortical volume, smaller ventricles, and asymmetry in the dorsal hippocampus, accompanied by neuronal loss. BTBR mice also showed impaired cerebrospinal fluid dynamics, with reduced production and outflow. Molecular analysis revealed brain region-specific reduction in the expression of Bdnf exons 1, 2, 3, and 4 in untrained BTBR mice. Furthermore, learning induced changes in transcription of Bdnf exons exclusively in BTBR. Elevated proBDNF levels and an increased proBDNF/mature BDNF ratio in the frontal cortex and striatum indicated aberrant BDNF processing. These findings suggest that ASD-related cognitive impairments are linked to a complex of neurodevelopmental abnormalities, potentially connected to disrupted transcription, processing, and signaling of BDNF. Show less

Autophagy and apoptosis are cellular processes that maintain cellular homeostasis and remove damaged or aged organelles or aggregated and misfolded proteins. Stress factors initiate the signaling pathways common to autophagy and apoptosis. An imbalance in the autophagy and apoptosis, led by cascade of molecular mechanism prior to both processes culminate into neurodegeneration. In present study, we urge to investigate the codon usage pattern of genes which are common before initiating autophagy and apoptosis. In the present study, we took up eleven genes (DAPK1, BECN1, PIK3C3 (VPS34), BCL2, MAPK8, BNIP3 L (NIX), PMAIP1, BAD, BID, BBC3, MCL1) that are part of molecular signaling mechanism prior to autophagy and apoptosis. We analyzed dinucleotide odds ratio, codon bias, usage, context, and rare codon analysis. CpC and GpG dinucleotides were abundant, with the dominance of G/C ending codons as preferred codons. Clustering analysis revealed that MAPK8 had a distinct codon usage pattern compared to other envisaged genes. Both positive and negative contexts were observed, and GAG-GAG followed by CTG-GCC was the most abundant codon pair. Of the six synonymous arginine codons, two codons CGT and CGA were the rarest. The information presented in the study may be used to manipulate the process of autophagy and apoptosis and to check the pathophysiology associated with their dysregulation. Show less