Biology subjects

Rodriguez Parkitna, J. M.

Publications and source records attributed to Rodriguez Parkitna, J. M..

4 recordsLinked to original sources

bioRxiv2025

Risperidone regulates the expression of schizophrenia-related genes in the murine forebrain

Risperidone acts on monoaminergic signaling to alleviate psychosis. At the cellular level, through both direct and indirect effects, the drug induces a specific pattern of gene expression, which differs between the basal ganglia and frontal cortex. These risperidone-regulated changes influence neuronal plasticity and are crucial for both its antipsychotic and extrapyramidal effects. Here, we employed sequencing-based spatial transcriptomics to comprehensively characterize gene expression changes in the male mouse (Mus musculus L.) forebrain after an acute dose of risperidone (0.5 mg/kg, i.p.). The transcriptional patterns were structure-specific, and unsupervised clustering of spatial profiles accurately identified cortical divisions, layers, and basal ganglia subregions. Differential gene expression was subsequently analyzed within each anatomically defined cluster using a customized statistical framework. Risperidone significantly altered the levels of 95 transcripts across 12 brain regions. The largest number of changes was observed in ventral brain areas, including the olfactory tubercle (25 differentially regulated transcripts), the diagonal band nucleus (22), the corpus callosum and commissures (13), and the lateral septal nucleus (9). Notably, 21 of the 95 differentially expressed genes were previously associated with schizophrenia, including Olig2, Smpd3, and Cacna1i. Overall, our results indicate that the strongest effects of risperidone are in medial and ventral brain regions rich in oligodendrocytes and glial cells. Furthermore, the enrichment analysis provides robust evidence of a molecular link between the drugs mechanism of action and genetic factors involved in schizophrenia. HighlightsO_LIUnsupervised clustering accurately identifies transcripts localization in the brain C_LIO_LIAcute risperidone treatment alters spatial transcriptional patterns of 95 genes C_LIO_LIRisperidone-regulated transcripts include 21 genes previously linked to schizophrenia C_LIO_LISpatial gene expression analysis offers novel insight into the drug action mechanism C_LI

pharmacology and toxicology↗

bioRxiv2025

Changes in social reward across adolescence in male mice

In humans, adolescence is a time of dynamic behavioral and emotional changes, including a transient decrease in affect associated with being among family members. It is not clear if a similar change occurs in rodent species used to model human psychiatric disorders. Here, we investigated the developmental profile of the rewarding value of interactions with siblings across adolescence in male mice, using the social conditioned place preference task. We found that the reward value of social interactions followed a similar course to that in humans: high in early adolescence, it decreased in mid-adolescence and returned to the initial level in late adolescence. The observed change was specific to social interaction, as no age-dependent changes in preference for cocaine-conditioned context were detected. Taken together, these data show similarities between mice and humans in developmental changes in sensitivity to the rewarding effects of interactions with familiar kin.

neuroscience↗

bioRxiv2023

Nonmotor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson's disease

Parkinsons disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse nonmotor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the nonmotor symptoms of PD in a mouse model of the disease (the TIF-IADATCreERT2 strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the step cadence and sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent nonmotor symptoms that emerge in the early stages of dopaminergic neuron degeneration.

neuroscience↗

bioRxiv2020

Loss of mu and delta opioid receptors on neurons expressing dopamine receptor D1 has no effect on reward sensitivity

Opioid signaling controls the activity of the brains reward system. It is involved in signaling the hedonic effects of rewards and also has essential roles in reinforcement and motivational processes. Here, we focused on opioid signaling through mu and delta receptors on dopaminoceptive neurons and evaluated the role these receptors play in reward-driven behaviors. We generated a genetically modified mouse with selective double knockdown of mu and delta opioid receptors in neurons expressing dopamine receptor D1. Selective expression of the transgene was confirmed using immunostaining. Knockdown was validated by measuring the effects of selective opioid receptor agonists on neuronal membrane currents using whole-cell patch clamp recordings. We found that in the nucleus accumbens of control mice, the majority of dopamine receptor D1-expressing neurons were sensitive to a mu or delta opioid agonist. In mutant mice, the response to the delta receptor agonist was blocked, while the effects of the mu agonist were strongly attenuated. Behaviorally, the mice had no obvious impairments. The mutation did not affect sensitivity to the rewarding effects of morphine injections or social contact and had no effect on preference for sweet taste. Knockdown had a moderate effect on motor activity in some of the tests performed, but this effect did not reach statistical significance. Thus, we found that knocking down mu and delta receptors on dopamine receptor D1-expressing cells does not appreciably affect reward-driven behaviors. Highlights- It is well accepted that opioid signaling controls the brains reward system - We generated mutant mice with mu and delta receptor knockdown in D1 neurons - Knockdown made dopaminoceptive neurons insensitive to mu and delta opioid receptor agonists - The mutation did not cause obvious behavioral impairments - The loss of mu and delta receptors on D1 neurons does not affect reward sensitivity

neuroscience↗