scholarly journals Parvalbumin loss following chronic sub-anesthetic NMDA antagonist treatment is age-dependent in the hippocampus: Implications for modeling NMDA hypofunction

2018 ◽  
Author(s):  
Jennifer A. Honeycutt ◽  
James J. Chrobak
Keyword(s):  
Calcium Binding ◽  
Nmda Antagonist ◽  
Adult Rats ◽  
Consistent Finding ◽  
Cell Counts ◽  
Age Dependent ◽  
Old Rats ◽  
Behavioral Impairments ◽  
The Impact ◽  
Effect Of Age

AbstractA marked decrease in parvalbumin (PV), a calcium-binding protein specific to a subset of GABAergic neurons, is a consistent finding in postmortem schizophrenic brain tissue. This reduction is selective to PV and is regionally specific: occurring primarily in the prefrontal cortex and hippocampus (HPC) of patients. Rodent models of NMDA receptor hypofunction utilizing NMDA antagonist treatments – e.g. ketamine (KET) – show schizophrenia-like cognitive and behavioral impairments with parallel changes in PV. While decreased PV is considered a hallmark of neuropathology in schizophrenia, previous work elucidating the effects of KET administration on PV are contradictory, with findings suggesting decreased, increased, or no change in PV expression. Upon close examination of the procedures used across studies, there are two primary inconsistencies, including: 1) the age of animals used; and 2) the timeline of post-treatment tissue collection. To better understand whether these key differences impact observed PV changes, the present study investigated the impact of age and time of sacrifice on chronic KET-induced PV changes in the neocortex and HPC. Our findings suggest an effect of age, but not sacrifice timeline, on PV cell count following 14 days of sub-anesthetic KET treatment. We provide evidence that 1-month-old rats exhibit significant KET-induced HPC PV decreases, while adult rats show a modest increase in HPC PV following chronic KET. Taken together, we propose that PV is a dynamic marker, and that changes in cell counts - and their interpretation - following NDMA antagonist treatment should be considered in the context of age.

Alveolar macrophage depletion is associated with increased surfactant pool sizes in adult rats

2007 ◽  
Vol 103 (2) ◽  
pp. 637-645 ◽  
Author(s):  
Amy Forbes ◽  
Mike Pickell ◽  
Mehry Foroughian ◽  
Li-Juan Yao ◽  
James Lewis ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Cell Counts ◽  
And Function ◽  
The Impact ◽  
Pool Sizes

Pulmonary surfactant is a lipid-protein material that is essential for normal lung function. Maintaining normal and consistent alveolar amounts of surfactant is in part dependent on clearance of surfactant by alveolar macrophages (AM). The present study utilized a rat model of AM depletion to determine the impact on surfactant pool sizes and function over time. Male Sprague-Dawley rats were anesthetized and intratracheally instilled with PBS-liposomes (PBS-L) or dichloromethylene diphosphonic acid (DMDP) containing liposomes (DMDP-L) and were killed at various time points up to 21 days for compliance measurements, AM cell counts, and surfactant analysis. AM numbers were significantly decreased 1, 2, and 3 days after instillation in DMDP-L vs. PBS-L, with 72% depletion at 3 days. AM numbers returned to normal levels by 5 days. In DMDP-L rats, there was a rapid increase in surfactant-phospholipid pools, showing a ninefold increase in the amount of surfactant in the lavage 3 days after liposome instillation. Surfactant accumulation progressed up to 7 days, with pools normalizing by 21 days. The increase in surfactant was due to increases in both subfractions of surfactant, the large aggregates (LA) and small aggregates. Surfactant protein A levels, relative to LA phospholipids, were not increased. There was a decreased extent of surfactant conversion in vitro for LA from DMDP-L rats compared with controls. It is concluded that the procedure of AM depletion significantly affects surfactant metabolism. The increased endogenous surfactant must be considered when utilizing the AM depletion model to study the role of these cells during lung insults.

Age effect on expression of myosin heavy and light chain isoforms in suspended rat soleus muscle

1999 ◽  
Vol 86 (5) ◽  
pp. 1483-1489 ◽  
Author(s):  
Ayako Saitoh ◽  
Tadashi Okumoto ◽  
Hiroshi Nakano ◽  
Masanobu Wada ◽  
Shigeru Katsuta
Keyword(s):  
Light Chain ◽  
Differential Effect ◽  
Skeletal Muscles ◽  
Age Effect ◽  
Hindlimb Suspension ◽  
Adult Rats ◽  
Age Dependent ◽  
Rat Soleus Muscle ◽  
Old Rats ◽  
Fast Twitch

This study was designed to test the hypothesis that myosin heavy (MHC) and light chain (MLC) plasticity resulting from hindlimb suspension (HS) is an age-dependent process. By using an electrophoretic technique, the distribution of MHC and MLC isoforms was quantitatively evaluated in the soleus muscles from 3- or 12-wk-old rats after 1–3 wk of HS treatment was maintained. In normal 12- and 15-wk-old rats, the soleus muscles contained a predominance of MHCI (∼94%) with small amounts of MHCIIa, but not MHCIId or MHCIIb. The suspended muscles of adult rats were characterized by the appearance of MHCIIb and MHCIId, the latter reaching ∼6% after 3 wk of HS treatment. In contrast to changes in MHC, HS did not induce a transition in the MLC pattern in the soleus muscles from adult rats. Compared with adult rats, in juveniles HS had a much more pronounced effect on the shift toward faster MHC and MLC isoform expression. The soleus muscles of 6-wk-old rats after 3 wk of HS were composed of 37.0% MHCI, 19.1% MHCIIa, 23.7% MHCIId, and 20.2% MHCIIb. Changes in MLC isoforms consisted of an increase in MLC1fand MLC2f concomitant with a decrease in MLC2s. These results indicate the existence of a differential effect of HS on MHC and MLC transitions that appears to be age dependent. They also suggest that the suspended soleus muscles from young rats may acquire the intrinsic contractile properties that are intermediate between those in the normal soleus and typical fast-twitch skeletal muscles.

scholarly journals Anticonvulsant action of GABA-B receptor agonist SKF97541 differs from that of Baclofen

2008 ◽  
pp. 789-792
Author(s):  
P Mareš
Keyword(s):  
Receptor Agonist ◽  
Age Groups ◽  
Mixed Effects ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Generalized Seizures ◽  
Age Dependent ◽  
Old Rats ◽  
Clonic Seizures ◽  
Tonic Phase

GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups.

scholarly journals Identification of Early Response Genes and Pathway Activated by Androgens in the Initial Segment and Caput Regions of the Regressed Rat Epididymis

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4504-4514 ◽  
Author(s):  
Mahsa Hamzeh ◽  
Bernard Robaire
Keyword(s):  
Growth Factor ◽  
Calcium Binding ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Early Time ◽  
Early Response ◽  
Adult Rats ◽  
Igf I ◽  
Rat Epididymis ◽  
The Impact

To identify the initial response to androgens and estrogens in the orchidectomized, regressed epididymis, we determined the gene expression changes triggered by the administration of either of two metabolites of testosterone, 5α-dihydrotestosterone (DHT) or 17β-estradiol (E2), in the regressed rat epididymis. Adult rats were orchidectomized and 8 d later implanted with either empty implants (control), DHT-filled-, or E2-filled-polydioxanone implants. Rats were euthanized 12 h, 1 d, and 7 d later, and RNA was extracted and probed on Rat230–2.0 Affymetrix arrays. Probe sets that respond to DHT or E2 were identified at early time points; although the expression of some was repressed, the expression of many others was either transiently or chronically elevated. Nerve growth factor receptor (Ngfr) and S100 calcium binding protein G (S100g) were two E2 up-regulated genes detected at 12 h. Among the genes that showed a dramatic early response to DHT were endothelin 1 (Edn1), bone morphogenetic protein 4 (Bmp4), and IGF binding protein 3 (Igfbp3), which were suppressed, and IGF-I (Igf1), which was induced. Genes that were up- or down-regulated by DHT were classified based on biological function. Using PathwayStudio 4.0, we identified genes that were linked and directly influenced either the expression or regulation of one another. Epidermal growth factor and IGF-I play an important role in the pathway due to their function in regulation and expression of many other genes. These results provide novel insights into the impact of androgen action on the expression of genes that are important for epididymal function.

scholarly journals Influence of the age of rats treated with the sodium salt of glutamate acid on the reactivity of astroglia of the infundibular nucleus

2017 ◽  
Vol 73 (4) ◽  
pp. 234-238
Author(s):  
Aleksandra Ewa Krawczyk ◽  
Jadwiga Jaworska-Adamu
Keyword(s):  
Nervous System ◽  
Glial Fibrillary Acidic Protein ◽  
Sodium Salt ◽  
Monosodium Glutamate ◽  
Adult Rats ◽  
Ki 67 ◽  
Specific Antibodies ◽  
Old Rats ◽  
The Impact ◽  
Number Of Cells

The aim of the study was the immunohistochemical evaluation of the impact of the age of animals treated with the sodium salt of glutamic acid on the behaviour of astrocytes of the infundibular nucleus (IN). Immunohistochemical peroxidase-antiperoxidase reactions were conducted on brain sections of 10-day-old (I) and 63-day-old (II) rats treated s.c with monosodium glutamate (MSG) in a dose of 4g/kg b.w. for three consecutive days. The staining was performed using specific antibodies against glial fibrillary acidic protein (GFAP), S-100β protein and Ki-67 antigen. Cells immunopositive for the proteins under investigation were assessed morphologically and morphometrically in an Olympus BX51 light microscope with the Cell ^ D program. Statistically significant differences were tested using ANOVA and the non-parametric Kruskal-Wallis test. In the infundibular nucleus of 10-day-old rats treated with MSG, there was an increase in the number of GFAP, S-100β and Ki-67 immunopositive astrocytes without any changes in their morphology, which was typical of immature glia. In adult rats treated with MSG, a decrease in the number of cells expressing GFAP and S-100β was found. Most astrocytes had thick and weakly branched processes, in contrast to those observed in control animals. The results of our study showed a diverse behaviour of astroglia of IN in young and adult rats treated with MSG. In 10-day-old rats, hyperplasia of glia occurred, whereas in 63-day-old individuals there was a loss and hypertrophy of astrocytes, which may indicate a late stage of their reactivity. This information may contribute to targeting the therapy of diseases of the nervous system induced by the excitotoxic effects of glutamate.

scholarly journals A stochastic, individual-based model for the evaluation of the impact of non-pharmacological interventions on COVID-19 transmission in Slovakia

2020 ◽  
Author(s):  
Miroslav Gasparek ◽  
Michal Racko ◽  
Michal Dubovsky
Keyword(s):  
Population Distribution ◽  
Pharmacological Interventions ◽  
Individual Based Model ◽  
Social Distancing ◽  
Proposed Model ◽  
Population Reduction ◽  
The Social ◽  
Age Dependent ◽  
The Impact ◽  
Effect Of Age

The COVID-19 pandemic represents one of the most significant healthcare challenges that humanity faces. We developed a stochastic, individual-based model of transmission of COVID-19 in Slovakia. The proposed model is based on current clinical knowledge of the disease and takes into account the age structure of the population, distribution of the population into the households, interactions within the municipalities, and interaction among the individuals travelling between municipalities. Furthermore, the model incorporates the effect of age-dependent severity of COVID-19 and realistic trajectories of patients through the healthcare system. We assess the impact of the governmental non-pharmacological interventions, such as population-wide social distancing, social distancing within specific subsets of population, reduction of travel between the municipalities, and self-quarantining of the infected individuals. We also evaluate the impact of relaxing of strict restrictions, efficacy of the simple state feedback-based restrictions in controlling the outbreak, and the effect of superspreaders on the disease dynamics. Our simulations show that non-pharmacological interventions reduce the number of infected individuals and the number of fatalities, especially when the social distancing of particularly susceptible subgroups of the population is employed along with case isolation.

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Protective Role ◽  
Albino Rats ◽  
Distilled Water ◽  
Negative Effects ◽  
Adult Rats ◽  
Stress Damage ◽  
The Impact ◽  
Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

The Impact of Financial Literacy on Financial Preparedness for Retirement in the Small and Medium Enterprises Sector in Uganda

2020 ◽  
Vol 9 (3) ◽  
pp. 26-41
Author(s):  
Colin Agabalinda ◽  
Alain Vilard Ndi Isoh
Keyword(s):  
Financial Literacy ◽  
Small And Medium Enterprises ◽  
Group Analysis ◽  
Moderating Effect ◽  
Primary Data ◽  
Retirement Preparedness ◽  
Medium Enterprises ◽  
The Impact ◽  
The Relationship ◽  
Effect Of Age

The study investigated the direct effects of financial literacy (knowledge, skills, and attitudes) on financial preparedness for retirement and the moderating effect of age among the small and medium enterprises in Uganda. Primary data was collected from a sample of n = 380 selected from the SME workforce. Descriptive analysis was run on SPSS, while validity and reliability of the measurement items yielded satisfactory composite reliability scores and average variance explained (AVE) scores for all items. Structural equation modelling (SEM) was used to test the hypotheses and multi-group analysis conducted to test for the moderating effect of age on the relationship between financial literacy and retirement preparedness. The results revealed that knowledge and skills were significant predictors of retirement preparedness. However, ‘attitude' was not a significant predictor, and age had no moderating effect on the relationship between the study variables. These findings present practical implications for policymakers and financial educators in a developing country context.

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 Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure

2021 ◽  
Author(s):  
Susanna M. Wallerstedt ◽  
Karin Nylén ◽  
Magnus A. B. Axelsson
Keyword(s):  
Bariatric Surgery ◽  
Antiepileptic Drugs ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Consistent Finding ◽  
Low Calorie ◽  
Post Surgery ◽  
Low Calorie Diet ◽  
Calorie Diet ◽  
The Impact

Abstract Purpose As a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations. Methods In a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered. Results In all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6–17 individuals, 11 substances: 1–4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: −0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself. Conclusions Serum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

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