Preferencje help
Polish version English version Język
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 2

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
1

Analysis of morphine-induced gene expression in the mouse hippocampus

100%
Barut J., Skupio U., Marut L., Tertil M., Golda S., Przewlocki R.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr Suppl.1
INTRODUCTION: Exposure to drugs of abuse initiates molecular alterations in the central nervous system that lead to an increased overall tenderness to addiction with subsequent drug exposures. These drug-induced alterations employ changes in gene expression, which may underlie the behavioral aberrancy that define a state of addiction. AIM(S): To identify the specific transcriptional alterations in different stages of morphine addiction in the hippocampus (Hip), brain region which play a role in the acquisition and extinction of memories associated with drug seeking behavior. METHOD(S): C57BL/6J male mice were injected twice daily for 3 weeks with morphine (increasing doses, 20-100 mg/kg i.p.). Animals were observed for spontaneous signs of withdrawal and behavior was measured in first and third week of abstinence. Morphine induced gene expression in the Hip was analyzed, using the qPCR technology. RESULTS: 24 h after chronic treatment we have observed spontaneous withdrawal syndrome and the peak of corticosterone levels in blood. Morphine-abstinent mice exhibited a variety of depression-like behaviors and cognitive deficits. Analyzes of Hip transcriptional responses to morphine indicated that most of genes regulated by morphine injection are GR-dependent, with a number of them being astrocyte‑specific (Gjb6, Plin4, Slc1a3, Gfap, Gja1). Analyzed genes clustered into few co-expressed groups, i.a. GR-dependent (Fkbp5, Tsc22d3, Zbtb16, Plin4) and activity-dependent (Fos, Fosl2) both upregulated in single and chronic exposure to morphine. Interestingly, 3-weeks abstinent mice didn’t exhibit any significant difference in transcription, but single dose of morphine (relapse) trigger sensitization of expression of some interesting genes (camk1g, Fosl2, Arc). CONCLUSIONS: Our results reveal that morphine induces drug‑specific transcriptional signatures in the Hip. Stress systems in Hip may modify the reward circuit through GR-dependent molecular pathways and this mechanism may be a fundamental for addiction therapy research. FINANCIAL SUPPORT: Polish National Science Centre Grant number 2013/08/A/NZ3/00848.
2

Evaluation of transgenic mice with progressive degeneration of noradrenergic system towards the study of presymtomatic phase of Parkinson's disease

84%
Barut J., Chmielarz P., Jurga A., Baginska M., Parlato R., Domanskyi A., Nalepa I., Kreiner G.
Acta Neurobiologiae Experimentalis
|
2019
|
tom 79
|
nr Suppl.1
Parkinson’s disease (PD) is characterized by an inevitable loss of dopaminergic cells.However, examination of human brain tissues revealed that noradrenergic cell loss in the region of the locus coeruleus (LC) may proceed and may be even greater than dopaminergic degeneration. AIM(S): The aim of this study was to determine whether genetically evoked, selective loss of LC noradrenergic neurons in a progressive manner may negatively influence the dopaminergic system. Our mice models have progressive degeneration of the noradrenergic system, based on deletion of the gene Rrn3 encoding transcription factor TIF-IA, which is essential for the regulation of rRNA synthesis. METHOD(S): First, we applied the conditional inactivation of the Rrn3 by the Cre-loxP system expressing Cre recombinase under DBH promoter. TIF‑IADBHCre mice revealed ptosis, reduced locomotor activity, and a shortened life span associated with enhanced expression of various neurodegenerative markers within the dopaminergic system, including upregulation of micro- and astroglia, pro-inflammatory proteins, and enhanced level of oxidative stress. To limit mutations to the CNS, in a second model a Cre-dependent lentiviral vector carrying the Rrn3 deletion created by the CRISPR/Cas9 system was directly delivered to LC of DBHCre mice. RESULTS: Our construct was first successfully tested in vitro on primary dopamine neurons followed by in vivo stereotactic application. This approach seems to be successful as, in preliminary data, we observed the disintegration of nucleoli in transduced noradrenergic neurons in LC, which is the determinant of the functional impairment of the targeted TIF‑IA. CONCLUSIONS: To-date, there are no experimental studies on possible long-term negative impacts of progressive noradrenergic degeneration on other neurotransmitter systems, despite the clinically observed concomitant loss of SN/VTA and LC neurons in PD. If we provide additional evidence, mice with ongoing neurodegeneration of LC neurons may became a valuable tool for studying the presymptomatic phase of PD.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.