Percutaneous electrolysis is an emerging intervention proposed for the management of tendinopathies. Tendon pathology is characterized by a significant cell response to injury and gene expression. No study investigating changes in expression of those genes associated with collagen regeneration and remodeling of extracellular matrix has been conducted. The aim of this pilot study was to investigate gene expression changes after the application of percutaneous electrolysis on experimentally induced Achilles tendinopathy with collagenase injection in an animal model. Fifteen Sprague Dawley male rats were randomly divided into three different groups (no treatment vs. percutaneous electrolysis vs. needling). Achilles tendinopathy was experimentally induced with a single bolus of collagenase injection. Interventions consisted of 3 sessions (one per week) of percutaneous electrolysis or just needling. The rats were euthanized, and molecular expression of genes involved in tendon repair and remodeling, e.g., Cox2, Mmp2, Mmp9, Col1a1, Col3a1, Vegf and Scx, was examined at 28 days after injury. Histological tissue changes were determined with hematoxylin–eosin and safranin O analyses. The images of hematoxylin–eosin and Safranin O tissue images revealed that collagenase injection induced histological changes compatible with a tendinopathy. No further histological changes were observed after the application of percutaneous electrolysis or needling. A significant increase in molecular expression of Cox2, Mmp9 and Vegf genes was observed in Achilles tendons treated with percutaneous electrolysis to a greater extent than after just needling. The expression of Mmp2, Col1a1, Col3a1, or Scx genes also increased, but did not reach statistical significance. This animal study demonstrated that percutaneous electrolysis applied on an experimentally induced Achilles tendinopathy model could increase the expression of some genes associated with collagen regeneration and remodeling of extracellular matrix. The observed gene overexpression was higher with percutaneous electrolysis than with just needling.

A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS. Microarray analysis showed 254 genes whose expression was identified as different by at least 1.3 fold change following chronic morphine exposure as compared to controls. Of these, several novel genes (grb2, copb2, otpb, magi1b, grik-l, bnip4 and sox19b) have been detected for the first time in an experimental animal model treated with morphine. We have also identified a subset of genes (dao.1, wls, bnip4 and camk1γb) differentially expressed by chronic morphine exposure whose expression is related to mu opioid receptor gene expression. Altered expression of copb2, bnip4, sox19b, otpb, dao.1, grik-l and wls is indicative of modified neuronal development, CNS patterning processes, differentiation and dopaminergic neurotransmission, serotonergic signaling pathway, and glutamatergic neurotransmission. The deregulation of camk1γb signaling genes suggests an activation of axonogenesis and dendritogenesis. Our study identified different functional classes of genes and individual candidates involved in the mechanisms underlying susceptibility to morphine actions related to CNS development. These results open new lines to study the treatment of pain and the molecular mechanisms involved in addiction. We also found a set of zebrafish-specific morphine-induced genes, which may be putative targets in human models for addiction and pain processes.

The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration more than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression-regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs.

The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca) is a model of audiogenic seizures with the epileptogenic focus localized in the inferior colliculus (IC). The sound-induced seizures exhibit a short latency (7–9 s), which implies innate protein disturbances in the IC as a basis for seizure susceptibility and generation. Here, we aim to study the protein profile in the GASH/Sal IC in comparison to controls. Protein samples from the IC were processed for enzymatic digestion and then analyzed by mass spectrometry in Data-Independent Acquisition mode. After identifying the proteins using the UniProt database, we selected those with differential expression and performed ontological analyses, as well as gene-protein interaction studies using bioinformatics tools. We identified 5254 proteins; among them, 184 were differentially expressed proteins (DEPs), with 126 upregulated and 58 downregulated proteins, and 10 of the DEPs directly related to epilepsy. Moreover, 12 and 7 proteins were uniquely found in the GASH/Sal or the control. The results indicated a protein profile alteration in the epileptogenic nucleus that might underlie the inborn occurring audiogenic seizures in the GASH/Sal model. In summary, this study supports the use of bioinformatics methods in proteomics to delve into the relationship between molecular-level protein mechanisms and the pathobiology of rodent models of audiogenic seizures.

Epilepsy is a neurological disorder characterized by abnormal neuronal excitability, with glutamate playing a key role as the predominant excitatory neurotransmitter involved in seizures. Animal models of epilepsy are crucial in advancing epilepsy research by faithfully replicating the diverse symptoms of this disorder. In particular, the GASH/Sal (genetically audiogenic seizure-prone hamster from Salamanca) model exhibits seizures resembling human generalized tonic-clonic convulsions. A single nucleotide polymorphism (SNP; C9586732T, p.His289Tyr) in the Grik1 gene (which encodes the kainate receptor GluK1) has been previously identified in this strain. The H289Y mutation affects the amino-terminal domain of GluK1, which is related to the subunit assembly and trafficking. We used confocal microscopy in Xenopus oocytes to investigate how the H289Y mutation, compared to the wild type (WT), affects the expression and cell-surface trafficking of GluK1 receptors. Additionally, we employed the two-electrode voltage-clamp technique to examine the functional effects of the H289Y mutation. Our results indicate that this mutation increases the expression and incorporation of GluK1 receptors into an oocyte’s membrane, enhancing kainate-evoked currents, without affecting their functional properties. Although further research is needed to fully understand the molecular mechanisms responsible for this epilepsy, the H289Y mutation in GluK1 may be part of the molecular basis underlying the seizure-prone circuitry in the GASH/Sal model.