scholarly journals Age-Dependent and Pathway-Specific Bimodal Action of Nicotine on Synaptic Plasticity in the Hippocampus of Mice Lacking the miR-132/212 Genes

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 261
Author(s):  
Tamara Stojanovic ◽  
David Velarde Gamez ◽  
Gabor Jorrid Schuld ◽  
Daniel Bormann ◽  
Maureen Cabatic ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nicotine Addiction ◽  
Adult Brain ◽  
Memory Storage ◽  
Synaptic Potentiation ◽  
Wild Type ◽  
Self Administration ◽  
Mature Adult ◽  
Age Dependent ◽  
The Impact

Nicotine addiction develops predominantly during human adolescence through smoking. Self-administration experiments in rodents verify this biological preponderance to adolescence, suggesting evolutionary-conserved and age-defined mechanisms which influence the susceptibility to nicotine addiction. The hippocampus, a brain region linked to drug-related memory storage, undergoes major morpho-functional restructuring during adolescence and is strongly affected by nicotine stimulation. However, the signaling mechanisms shaping the effects of nicotine in young vs. adult brains remain unclear. MicroRNAs (miRNAs) emerged recently as modulators of brain neuroplasticity, learning and memory, and addiction. Nevertheless, the age-dependent interplay between miRNAs regulation and hippocampal nicotinergic signaling remains poorly explored. We here combined biophysical and pharmacological methods to examine the impact of miRNA-132/212 gene-deletion (miRNA-132/212−/−) and nicotine stimulation on synaptic functions in adolescent and mature adult mice at two hippocampal synaptic circuits: the medial perforant pathway (MPP) to dentate yrus (DG) synapses (MPP-DG) and CA3 Schaffer collaterals to CA1 synapses (CA3–CA1). Basal synaptic transmission and short-term (paired-pulse-induced) synaptic plasticity was unaltered in adolescent and adult miRNA-132/212−/− mice hippocampi, compared with wild-type controls. However, nicotine stimulation promoted CA3–CA1 synaptic potentiation in mature adult (not adolescent) wild-type and suppressed MPP-DG synaptic potentiation in miRNA-132/212−/− mice. Altered levels of CREB, Phospho-CREB, and acetylcholinesterase (AChE) expression were further detected in adult miRNA-132/212−/− mice hippocampi. These observations propose miRNAs as age-sensitive bimodal regulators of hippocampal nicotinergic signaling and, given the relevance of the hippocampus for drug-related memory storage, encourage further research on the influence of miRNAs 132 and 212 in nicotine addiction in the young and the adult brain.

Subtle Impact of Akt1 and Akt3 on Exploratory Behavior in Gene Targeted Mice

2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Wild Type ◽  
Average Speed ◽  
Closed Area ◽  
Light Area ◽  
Swimming Test ◽  
The Impact ◽  
Center Area ◽  
Dark Transition

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.

scholarly journals Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Titanium Dioxide ◽  
Genetic Risk ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Food Additive ◽  
Wild Type ◽  
Dextran Sodium Sulphate ◽  
Risk Gene ◽  
The Impact

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk

scholarly journals Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1625
Author(s):  
Theresa C. Sutherland ◽  
Arthur Sefiani ◽  
Darijana Horvat ◽  
Taylor E. Huntington ◽  
Yuanjiu Lei ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Traumatic Injury ◽  
Axon Growth ◽  
Neurite Growth ◽  
Growth Potential ◽  
Mitochondrial Functions ◽  
Cord Injury ◽  
Age Dependent ◽  
Mitochondria Functions ◽  
The Impact

The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

scholarly journals Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ammar Zaghlool ◽  
Adnan Niazi ◽  
Åsa K. Björklund ◽  
Jakub Orzechowski Westholm ◽  
Adam Ameur ◽  
...  
Keyword(s):  
Human Brain ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Adult Brain ◽  
Sequencing Data ◽  
Human Brain Tissue ◽  
Protein Coding ◽  
Rna Transcripts ◽  
Nuclear Rna ◽  
The Impact

AbstractTranscriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we separated cytosolic and nuclear RNA from human fetal and adult brain samples and performed a comprehensive analysis of cytosolic and nuclear transcriptomes. There are significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. We show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Differential expression analysis between fetal and adult frontal cortex show that results obtained from the cytosolic RNA differ from results using nuclear RNA both at the level of transcript types and the number of differentially expressed genes. Our data provide a resource for the subcellular localization of thousands of RNA transcripts in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for expression analysis.

scholarly journals Parkin regulates drug-taking behavior in rat model of methamphetamine use disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akhil Sharma ◽  
Arman Harutyunyan ◽  
Bernard L. Schneider ◽  
Anna Moszczynska
Keyword(s):  
Neural Substrates ◽  
Genetically Engineered ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Self Administration ◽  
Methamphetamine Use ◽  
New Therapeutic Approaches ◽  
Extended Access ◽  
High Doses ◽  
Methamphetamine Use Disorder

AbstractThere 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.

scholarly journals COVD-25. THE PARADOXICAL EFFECTS OF COVID-19 ON CANCER CARE IN THE NEURO-ONCOLOGY SETTING

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii26-ii26
Author(s):  
Nicole Cort ◽  
Alex Broom ◽  
Katherine Kenny ◽  
Alexander Page ◽  
Jennifer Durling ◽  
...  
Keyword(s):  
Cancer Care ◽  
Standard Of Care ◽  
Adult Brain ◽  
Evidence Based ◽  
Negative Consequences ◽  
Traditional Practice ◽  
Delivery Of Care ◽  
Paradoxical Effects ◽  
Oncology Care ◽  
The Impact

Abstract COVID-19 has caused ongoing interruptions to healthcare systems worldwide, shifting care to virtual platforms, and placing significant economic and logistical burdens on clinical practice. The pandemic has created uncertainty in delivering the standard of care, both in areas of cancer diagnosis and treatment, especially within neuro-oncology. Due to the pandemic, care and operational planning goals have shifted to infection prevention, modifying recommendations to decrease viral transmission and increasing telemedicine use, potentially creating a burden on implementing evidence-based medicine. These dynamics have since begun to redefine traditional practice and research regimens, impacting the comprehensive care that cancer patients can and should receive; and the enduring consequences for the delivery of healthcare. The impact of COVID-19 on oncology practice and trials might endure well beyond the short- to mid-term of the active pandemic. Therefore, these shifts must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care. To address these paradoxical effects, we will conduct iterative, qualitative (face-to-face/video conference) interviews with neuro-oncology clinical and research professionals and adult brain tumor patients receiving care during the pandemic. We will capture unique aspects of oncology care: the lived, subjective, situated, and contingent accounts of patients and medical professionals, especially during a pandemic. We will also specifically compare the impact of telehealth during the pandemic on delivery of care to complex neuro-oncology patients. A summary of this in-depth, qualitative approach will result in a sophisticated understanding of neuro-oncology care on the frontline at a time of crisis, as experienced during a pandemic, to articulate best practices for future implementation.

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