Biology subjects

Harutyunyan, A.

Publications and source records attributed to Harutyunyan, A..

3 recordsLinked to original sources

bioRxiv2022

Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy.

There are no pharmacological disease-modifying treatments that can mitigate the seizures and comorbidities associated with established chronic temporal lobe epilepsy (TLE). This study evaluated the effect of sodium selenate in the post-status epilepticus (SE) rat model of chronic drug resistant TLE. Wistar rats underwent kainic acid-induced SE or sham. Ten-weeks post-SE, rats were randomly assigned to receive either sodium selenate, levetiracetam, or vehicle treatments continuously for 4 weeks. To evaluate the effects of the treatments, 1 week of continuous video-EEG was acquired before, during, and 4, 8 weeks post-treatment, followed by behavioral tests. Targeted and untargeted proteomics and metabolomics were performed on post-mortem brain tissue to identify potential pathways associated with modified disease outcomes. Telomere length was investigated as a novel surrogate marker of disease severity. Sodium selenate treatment was able to mitigate disease severity, reducing the number of spontaneous seizures (p< 0.05), cognitive dysfunction (p< 0.05 in both novel object placement and recognition tasks), and sensorimotor deficits (p< 0.01) 8 weeks post-treatment cessation. Moreover, increased protein phosphatase 2A (PP2A) expression, reduced hyperphosphorylated tau, and reversed telomere length shortening caused by SE (p< 0.05). Network medicine integration of multi-omics/ pre-clinical outcomes identified protein-metabolite modules positively correlated with the TLE phenotype. Our results provide evidence that treatment with sodium selenate results in a sustained disease modifying effect in chronically epileptic rats in the post-KA SE model of TLE, including improved comorbid learning and memory deficits.

neuroscience↗

bioRxiv2020

PARKIN REGULATES DRUG TAKING-BEHAVIOR IN RAT MODEL OF METHAMPHETAMINE USE DISORDER

There is no FDA-approved medication for Methamphetamine (METH) Use Disorder. New therapeutic approaches are needed, especially for people who use METH heavily and are at high risk for overdose. This study used genetically engineered rats to evaluate PARKIN as a potential target for METH Use Disorder. PARKIN knockout, PARKIN-overexpressing and wild-type young adult male Long Evans rats were trained to self-administer high doses of METH using an extended-access METH self-administration paradigm. Reinforcing/rewarding properties of METH were assessed by quantifying drug-taking behavior and time spent in a METH-paired environment. PARKIN knockout rats self-administered more METH and spent more time in the METH-paired environment than wild-type rats. Wild-type rats overexpressing PARKIN self-administered less METH and spent less time in the METH-paired environment. PARKIN knockout rats overexpressing PARKIN self-administered less METH during the first half of drug self-administration days than PARKIN-deficient rats. The results indicate that rats with PARKIN excess or PARKIN deficit are useful models for studying neural substrates underlying "resilience" or vulnerability to METH Use Disorder, and identify PARKIN as a novel potential drug target to treat heavy use of METH.

neuroscience↗

bioRxiv2019

Persistence of neuronal representations through time and damage in the hippocampus.

Memories can persist for decades but how they are stably encoded in individual and groups of neurons is not known. To investigate how a familiar environment is encoded in CA1 neurons over time we implanted bilateral microendoscopes in transgenic mice to image the activity of pyramidal neurons in the hippocampus over weeks. Most of the neurons (90 %) are active every day, however, the response of neurons to specific cues changes across days. Approximately 40 % of place and time cells lose fields between two days; however, on timescales longer than two days the neuronal pattern changes at a rate of 1 % for each additional day. Despite continuous changes, field responses are more resilient, with place/time cells recovering their fields after a 10-day period of no task or following CA1 damage. Recovery of these neuronal patterns is characterized by transient changes in firing fields which ultimately converge to the original representation. Unlike individual neurons, groups of neurons with inter and intrahemispheric synchronous activity form stable place and time fields across days. Neurons whose activity was synchronous with a large group of neurons were more likely to preserve their responses to place or time across multiple days. These results support the view that although task-relevant information stored in individual neurons is relatively labile, it can persist in networks of neurons with synchronized activity spanning both hemispheres. One Sentence SummaryNeuronal representations in networks of neurons with synchronized activity are stable over weeks, even after lack of training or following damage.

neuroscience↗