Biology subjects

Rodarte, D.

Publications and source records attributed to Rodarte, D..

5 recordsLinked to original sources

bioRxiv2025

MicroRNAs alteration and unique distribution in the soma and synapses of substantia nigra in Parkinsons disease

Parkinsons disease (PD) is the second most common neurodegenerative condition after Alzheimers. Abnormal accumulation of alpha-synuclein (-syn) aggregates disrupts the balance of dopaminergic (DA-ergic) synapse components, interfering with dopamine transmission and leading to synaptic dysfunction and neuronal loss in PD. However exact molecular mechanism underlying DA-ergic neuronal cell loss in the SNpc in not known. MicroRNAs (miRNAs) are observed in various compartments of neural elements including cell bodies, nerve terminals, mitochondria, synaptic vesicles and synaptosomes. However, miRNAs expression and cellular distribution are unknown in the soma and synapse compartment in PD and healthy state. To address this void of information, we isolated synaptosomes and cytosolic fractions (soma) from post-mortem brains of PD-affected individuals and unaffected controls (UC) and processed for miRNA sequencing analysis. A group of miRNAs were significantly altered (p < 0.05) with high fold changes (variance +/- > 2-fold) in their expressions in different comparisons: 1. UC synaptosome vs UC cytosol, 2. PD synaptosome vs PD cytosol, 3. PD synaptosome vs UC synaptosome, 4. PD cytosol vs UC cytosol. Our study unveiled some potential miRNAs in PD and their alteration and unique distribution in the soma and synapses of SNpc in PD and controls. Further, gene ontology enrichment analysis showed the involvement of deregulated miRNAs in several molecular function and cellular components: synapse assembly formation, cell junction organization, cell projections, mitochondria, Calcium ion binding and protein binding activities.

neuroscience↗

bioRxiv2025

Modulation of microRNA-502-3p significantly influences synaptic activity, dendritic spine density and mitochondrial morphology in the mice brain

Synapse dysfunction is the root cause of Alzheimers disease (AD). Uninterrupted and regulated synapse action is crucial to maintain healthy brain function. Our previous study discovered microRNA-502-3p (miR-502-3p), a synapse-specific miRNA, highly expressed at the AD synapses. Further, in vitro studies unveiled the biological relevance of miR-502-3p in modulating GABA receptor function, synaptic activity and mitochondrial morphology. Current study focuses to investigate the role of miR-502-3p in vivo using stereotaxic injection of miR-502-3p overexpression (OE) and suppression (sponge) lentivirus (LV) into the hippocampus of C57BL/6 wild-type (WT) mice. MiR-502-3p OE and sponge LV were characterized by transducing HT22 cells followed by QRT-PCR and miRNAScope analysis of miR-502-3p. MiR-502-3p OE LV showed a very high-fold upregulation and sponge LV showed significant reduction in miR-502-3p levels. MiR-502-3p OE and sponge LV were injected into three months old WT mice brain hippocampus. Overexpression and suppression effects of miR-502-3p were studied on synaptic proteins, synapse number, mitochondrial morphology and dendritic spine density at eight-weeks post-injection. Mice injected with miR-502-3p OE LV showed reduced levels of synaptic proteins, diminished synapse formation, defective mitochondrial morphology and reduced dendritic spine density relative to control LV treated mice. While mice treated with sponge LV showed elevated levels of synaptic proteins, augmented synapses, improved mitochondrial morphology and elongated dendrites and spine density. Our in vivo study unveiled translational abilities of miR-502-3p to restore synapse dysfunction in AD and other neurological disorders.

neuroscience↗

bioRxiv2025

Integrated Multi-Omics Analyses of Synaptosomes Revealed Synapse-Centered Novel Targets in Alzheimer's Disease

AO_SCPLOWBSTRACTC_SCPLOWSynapse dysfunction is an early event in Alzheimers disease (AD) caused by various factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. To understand this, we comprehensively analyzed the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. We conducted high-throughput transcriptomic analyses to identify changes in microRNA (miRNA) and mRNA levels in synaptosomes extracted from the brains of both unaffected individuals and those with Alzheimers disease (AD). Additionally, we performed mass spectrometry analysis of synaptosomal proteins in the same sample group. These analyses revealed significant differences in the levels of miRNAs, mRNAs, and proteins between the groups. To further understand the pathways or molecules involved, we used an integrated omics approach and studied the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the samples from individuals with AD and the control group, which demonstrated the impact of deregulated miRNAs on their target mRNAs and proteins. Furthermore, the DIABLO analysis highlighted complex relationships between mRNAs, miRNAs, and proteins that could be key in understanding the pathophysiology of AD. Our study identified synapse-centered novel candidates that could be critical in restoring synapse dysfunction in AD.

neuroscience↗

bioRxiv2025

MiRNA-501-3p and MiRNA-502-3p: A Promising Biomarker Panel for Alzheimer's Disease

INTRODUCTIONAlzheimers disease (AD) lacks a less invasive and early detectable biomarker. Here, we investigated the biomarker potential of miR-501-3p and miR-502-3p using different AD sources. METHODSMiR-501-3p and miR-502-3p expressions were evaluated in AD CSF exosomes, serum exosomes, familial and sporadic AD fibroblasts and B-lymphocytes by qRT-PCR analysis. Further, miR-501-3p and miR-502-3p expressions were analyzed in APP, Tau cells and media exosomes. RESULTSMiR-501-3p and miR-502-3p expressions were significantly upregulated in AD CSF exosomes relative to controls. MiRNA levels were high in accordance with amyloid plaque and NFT density in multiple brain regions. Similarly, both miRNAs were elevated in AD and MCI serum exosomes compared to controls. MiR-502-3p expression was high in fAD and sAD B-lymphocytes. Finally, miR-501-3p and miR-502-3p expression were elevated intracellularly and secreted extracellularly in response to APP and Tau pathology. DISCUSSIONThese results suggest that miR-501-3p and miR-502-3p could be promising biomarkers for AD.

neuroscience↗

bioRxiv2025

MicroRNA-502-3p modulates the GABA A subunits, synaptic proteins and mitochondrial morphology in hippocampal neurons

MicroRNA-502-3p (MiR-502-3p), a synapse enriched miRNA is considerably implicated in Alzheimers disease (AD). Our previous study found the high expression level of miR-502-3p in AD synapses relative to controls. Further, miR-502-3p was found to modulate the GABAergic synapse function via modulating the GABA A receptor subunit -1 (GABRA1) protein. The current study is attempted to examine the impact of miR-502-3p on other GABA subunit proteins, synaptic proteins, mitochondrial morphology and other hippocampal neuron genes. Mouse hippocampal neuronal (HT22) cells were transfected with miR-502-3p overexpression (OE) vector, miR-502-3p sponge (suppression) vector and scramble control vector. MiR-502-3p vectors transfection was confirmed by fluorescence microscopy. MiR-502-3p expression and GABRA1 expression was confirmed by qRT-PCR and miRNAScope in-situ hybridization. GABA A subunit and synaptic proteins were studied by immunoblotting analysis and mitochondrial morphology was analyzed by transmission electron microscopy (TEM) analysis. Further, Affymetrix gene array analysis was conducted in miR-502-3p overexpressed and suppressed cells. Our results observed that elevated miR-502-3p, negatively modulates the GABRA1 level. The levels of GABA A subunit and synaptic proteins were reduced by ectopic expression of miR-502-3p and increase by miR-502-3p suppression. The mitochondrial morphology was found to be improved in-terms of their number and length in miR-502-3p suppressed cells. Further, Gene array analysis unveiled the deregulation of several genes by miR-502-3p, which are associated with oxidative stress, immune response and synaptic function. These results provide new insights and an update to understand the biological roles of miR-502-3p in regulation of neuron function and synaptic activity.

neuroscience↗