scholarly journals Longitudinal characterization of neuroanatomical changes in the Fischer 344 rat brain during normal aging and between sexes

2021 ◽  
Author(s):  
Caitlin F Fowler ◽  
Dana Alexander Goerzen ◽  
Dan Madularu ◽  
Gabriel A Devenyi ◽  
Jamie Near ◽  
...  
Keyword(s):  
Brain Regions ◽  
Transgenic Models ◽  
Aging Research ◽  
Background Strain ◽  
Fischer 344 ◽  
Frequency Of Use ◽  
Control Circuits ◽  
Models Of Disease ◽  
F344 Rats

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is also one of the most frequently used models in aging research. Despite frequency of use, characterization of neuroanatomical change with age has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in a mixed-sex cohort of F344 rats. We identified age- and sex-related changes in regions such as the cortex, hippocampus, cingulum, caudoputamen, and nucleus accumbens, which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared.

scholarly journals Observations on Altered Hepatocellular Foci in National Toxicology Program Two-Year Carcinogenicity Studies in Rats

1989 ◽  
Vol 17 (4_part_1) ◽  
pp. 690-708 ◽  
Author(s):  
Takanori Harada ◽  
Robert R. Maronpot ◽  
Richard W. Morris ◽  
Gary A. Boorman
Keyword(s):  
Liver Tumor ◽  
Morphological Variability ◽  
Mixed Cell ◽  
Qualitative And Quantitative ◽  
Fischer 344 ◽  
National Toxicology Program ◽  
Hepatic Neoplasia ◽  
Quantitative Changes ◽  
F344 Rats

Retrospective characterization of morphological and stereological features of altered hepatocellular foci (AHF) in hematoxylin & eosin (H&E)-stained sections was performed on 6 conventional 2−yr carcinogenicity studies conducted in Fischer 344 (F344) rats by the National Toxicology Program (NTP). In 3 of these studies where there was clear evidence of hepatocarcinogenicity [1−amino−2,4−dibromoanthraquinone (ADBAQ), C.I. Acid Red 114, methyl carbamate], there was greater morphological variability in AHF than in the studies of chemicals that were not hepatocarcinogenic [4−hydroxyacetanilide, epinephrine, dimethoxane]. In addition to having the expected types of AHF, rats treated with ADBAQ, C.I. Acid Red 114, and methyl carbamate had atypical basophilic AHF. In addition, atypical eosinophilic AHF were present in rats treated with ADBAQ. Both types of atypical AHF showed a morphological spectrum and sequential changes suggesting they could develop into hepatocellular neoplasms. For the 3 liver tumor positive studies, there were dose-and time-dependent increases in stereological parameters for the atypical as well as commonly occurring clear, vacuolated, and mixed cell AHF. Consistent stereological changes were not found for commonly occurring basophilic and eosinophilic AHF. Aside from some decreases in stereological measurements in some rats treated with 4−hydroxyacetanilide and epinephrine, there were no significant quantitative changes in AHF in the three liver tumor negative studies. These results show that hepatocarcinogens may induce unique types of AHF in conventional 2−yr carcinogenicity/toxicity studies in rats and may cause quantitative increases in commonly occurring clear, vacuolated, and mixed cell AHF. Such qualitative and quantitative changes are potentially useful predictors of hepatic neoplasia.

Morphological and Stereological Characterization of Hepatic Foci of Cellular Alteration in Control Fischer 344 Rats

1989 ◽  
Vol 17 (4_part_1) ◽  
pp. 579-593 ◽  
Author(s):  
Takanori Harada ◽  
Robert R. Maronpot ◽  
Richard W. Morris ◽  
Katherine A. Stitzel ◽  
Gary A. Boorman
Keyword(s):  
Clear Cell ◽  
Volume Fraction ◽  
Fischer 344 Rats ◽  
Mixed Cell ◽  
Fischer 344 ◽  
High Incidence ◽  
Hematoxylin And Eosin ◽  
Males And Females ◽  
F344 Rats

Quantitative evaluation of altered hepatocellular foci (AHF), followed by stereological analysis was performed on standard hematoxylin and eosin-stained liver sections from control Fischer 344 (F344) rats of both sexes from seven 2-yr carcinogenicity studies conducted by the National Toxicology Program (NTP). Liver samples were collected at 6, 9, 12, 15, 18, and/or 24 months on study. Although AHF had a broad spectrum of morphological features, they could be classified into the following 5 types using previously published criteria: basophilic, eosinophilic, clear, vacuolated, and mixed cell foci. Approximately 50% of the animals had foci at 6 months, and the incidence reached nearly 100% at 15 months in both sexes. The number, size and volume fraction of AHF increased with age in both sexes; these changes were most evident for basophilic and clear cell foci. The number of basophilic foci was significantly greater in females than in males while clear cell foci were more numerous in males. This sex difference was observed at each time point. Mean number of all types of AHF in males and females at 24 months was 547 and 460 per cubic centimeter of liver, respectively. Despite the high incidence of AHF in control rats, the incidence of hepatocellular neoplasms is low. The implication is that most foci do not progress to neoplasia in control F344 rats used in 2-yr studies.

Cold-induced thermogenesis in younger and older Fischer 344 rats following exercise training

1988 ◽  
Vol 254 (6) ◽  
pp. R908-R916 ◽  
Author(s):  
R. B. McDonald ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Exercise Training ◽  
Body Mass ◽  
Cold Exposure ◽  
O2 Consumption ◽  
Fischer 344 ◽  
Before And After ◽  
Old Rats ◽  
F344 Rats ◽  
Maintain Body Temperature ◽  
Brown Fat Mitochondria

The inability of old rats to maintain body temperature during cold exposure has been well documented. This study evaluated the effect of exercise on the rates of cold-induced O2 consumption and the contribution of nonshivering thermogenesis (NST) to these rates. Younger (12 mo) and older (24 mo) male Fischer 344 (F344) rats were divided into exercised and sedentary groups. Exercised rats were run on a motor-driven treadmill 60 min/day, at 19-24 m/min, 5 days/wk for 6 mo. At the conclusion of the 6-mo training period, O2 consumption of all four groups was measured at thermoneutrality (26 degrees C) and during 6 h of exposure to 6 degrees C. Rectal temperatures were recorded before and after cold exposure. NST was estimated from the ability of isolated brown fat mitochondria to bind guanosine 5'-diphosphate (GDP). Core temperature of older sedentary rats fell 5.1 +/- 0.4 degrees C after cold exposure (36.3 +/- 0.3 vs. 31.2 +/- 0.8 degrees C). Exercise training in older animals prevented this fall from occurring (36.4 +/- 0.2 vs. 35.3 +/- 0.3 degrees C). Core temperatures of cold-exposed younger exercised and sedentary rats did not differ from thermoneutral values. Exercise did not alter the rates of resting body mass-independent (ml.min-1.kg body mass-0.67) O2 consumption in younger or older rats. However, body mass-independent and lean body mass (LBM)-independent (ml.min-1.g LBM-0.67) cold-induced O2 consumptions of older exercised rats were significantly elevated relative to those of older sedentary animals. This effect of exercise was not seen in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Subchronic Hepatotoxicity Evaluation of Hydrazobenzene in Fischer 344 Rats

2012 ◽  
Vol 31 (6) ◽  
pp. 564-571 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Henry G. Wall ◽  
Russell S. Thomas
Keyword(s):  
Body Weight ◽  
Serum Alkaline Phosphatase ◽  
Clinical Signs ◽  
Liver Weight ◽  
Fischer 344 ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Body Weights ◽  
Effect Level ◽  
F344 Rats

Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or 13 weeks duration. End points evaluated included clinical observations, body weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver histopathology. There were no HZB exposure-related clinical signs of toxicity. During study weeks 8 through 13, body weight means in rats of the 300 ppm group were 6% lower compared to control rat means. Serum alkaline phosphatase concentrations were decreased in rats of the 300 ppm group at all time points. Relative (to body weight) liver weight increases were observed in rats of the 200 and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13 weeks of exposure. Following 13 weeks of exposure, microscopic findings in the liver were observed only in rats of the 200 and 300 ppm groups and consisted of hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct duplication. Blood HZB concentrations ranged from 0.002 to 0.006 µg/mL in rats of the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per d) was selected based on the observation of microscopic hepatocyte alterations at ≥200 ppm HZB.

Artificial Intelligent Algorithm to control Circuits Structuring of Flexible remote Experiments in Engineering within a Switching Matrix Architecture

2021 ◽  
Vol 9 (2) ◽  
pp. 92-102
Keyword(s):  
Switching System ◽  
Electronic Components ◽  
Intelligent Algorithm ◽  
Artificial Intelligent ◽  
Physical Possibility ◽  
Electronic Board ◽  
Switching Matrix ◽  
E Learning ◽  
Control Circuits

This paper presents the development of an artificial intelligent algorithm to control circuits structuring of flexible remote experiments in engineering fields of electronics and electricity within a switching matrix architecture. In addition, this paper presents a technical analyze and characterization of VISIR system to point itsadvantages and its inconveniences.The developedartificial intelligent algorithm controlsthe interconnections between electrical and electronic components and monitorsthe power supplying and measurements conducting onVISIR system.We also developed an electronic board to provide the physical possibility of connecting any component to any other component on VISIR’s switching system, and thereby manifesting a switching matrix architecture within VISIR. The developed switching matrix architecture and the developed algorithm enable to have flexible remote experiments in engineeringfields of electronics and electricitywhile havingresilient control on circuits structuring for e-learning purposes.Inaddition, they open the way to havemore circuit combinations of experiments by offering the possibility of connecting any component to any other componentwhile respecting the electrical limits of current and voltage.

scholarly journals Novel Immunotherapeutic Approaches to Target Alpha-Synuclein and Related Neuroinflammation in Parkinson’s Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 105 ◽  
Author(s):  
Maria Zella ◽  
Judith Metzdorf ◽  
Friederike Ostendorf ◽  
Fabian Maass ◽  
Siegfried Muhlack ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Glial Cell ◽  
Dopaminergic Neurons ◽  
Basic Research ◽  
Alpha Synuclein ◽  
Models Of Disease ◽  
Novel Therapeutic Strategies ◽  
Lymphocyte Populations

The etiology of Parkinson’s disease (PD) is significantly influenced by disease-causing changes in the protein alpha-Synuclein (aSyn). It can trigger and promote intracellular stress and thereby impair the function of dopaminergic neurons. However, these damage mechanisms do not only extend to neuronal cells, but also affect most glial cell populations, such as astroglia and microglia, but also T lymphocytes, which can no longer maintain the homeostatic CNS milieu because they produce neuroinflammatory responses to aSyn pathology. Through precise neuropathological examination, molecular characterization of biomaterials, and the use of PET technology, it has been clearly demonstrated that neuroinflammation is involved in human PD. In this review, we provide an in-depth overview of the pathomechanisms that aSyn elicits in models of disease and focus on the affected glial cell and lymphocyte populations and their interaction with pathogenic aSyn species. The interplay between aSyn and glial cells is analyzed both in the basic research setting and in the context of human neuropathology. Ultimately, a strong rationale builds up to therapeutically reduce the burden of pathological aSyn in the CNS. The current antibody-based approaches to lower the amount of aSyn and thereby alleviate neuroinflammatory responses is finally discussed as novel therapeutic strategies for PD.

scholarly journals LONGITUDINAL CHARACTERIZATION OF NEUROANATOMICAL CHANGES IN THE FISCHER 344 RAT BRAIN DURING NORMAL AGING AND BETWEEN SEXES

2021 ◽  
Author(s):  
Caitlin Fowler ◽  
Dana Goerzen ◽  
Dan Madularu ◽  
Gabriel A. Devenyi ◽  
M. Mallar Chakravarty ◽  
...  
Keyword(s):  
Rat Brain ◽  
Normal Aging ◽  
Fischer 344 ◽  
Fischer 344 Rat

scholarly journals Dissection of neuroinflammation in schizophrenia

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S274-S275
Author(s):  
Fizah Muratib ◽  
Yuya Mizuno ◽  
Ines Carreira Figueiredo ◽  
Oliver Howes ◽  
Tiago Reis Marques
Keyword(s):  
Risk Factor ◽  
Grey Matter ◽  
Psychotic Disorders ◽  
Positive Association ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Cannabis Use ◽  
Similar Response ◽  
Frequency Of Use ◽  
The Brain

AimsSchizophrenia is notoriously becoming one of the world's most debilitating mental disorders, affecting 1 in 100 people. There is increasing evidence that neuroinflammation plays a part in the pathogenesis of schizophrenia and other psychotic disorders; microglial activity acting as a marker for neuroinflammatory reactions in the brain. Furthermore, cannabis is an illicit substance that also evokes a similar response in the neuroimmune activity. This project explores how cannabis exposure influences an elevation in neuroinflammatory responses through TSPO levels, and whether this information can help us determine if cannabis use and increased TSPO levels can be associated with a risk factor for developing psychosis.Method55 participants (36 males and 19 females) were recruited from the community by the IRIS (Inflammatory Reaction in Schizophrenia) team at the IoPPN, King's College London, from which 34 patients with a diagnosis of schizophrenia and 21 healthy controls took part in the study. The eligible participants underwent clinical assessments and PET scanning, from which cannabis use history and PET data were collected. Participant neuroinflammatory levels are represented by [18F]DPA-714 volume and different regions of grey matter in the brain were analysed through multivariate analyses, the confounding variables being age and TSPO genotype.ResultA statistically significant association is shown between participants who have had exposure to cannabis and participants who have not had any exposure in their lifetime. The differences across the prioritised brain regions of interest were robust, the association appearing more apparent and statistically significant in the total (p = .00) and temporal grey matter (p = .00) regions of the brain. This may suggest that cannabis exposure influences the [18F]DPA-714 VT in the significant regions of interest. However, a negative association is seen with current use, the quantity of use, and the frequency of use.ConclusionThe initial findings for cannabis exposure show us a positive association with increased TSPO levels, however, limitations must be taken into account. Although we cannot readily establish that elevated TSPO levels in cannabis users can presently act as a risk factor marker for developing psychosis from this particular study, we can utilise this data to continue our research in disclosing a new system to predict the occurrence of psychosis.

scholarly journals A Graphlet-Based Topological Characterization of the Resting-State Network in Healthy People

2021 ◽  
Vol 15 ◽  
Author(s):  
Paolo Finotelli ◽  
Carlo Piccardi ◽  
Edie Miglio ◽  
Paolo Dulio
Keyword(s):  
Resting State ◽  
Brain Regions ◽  
Brain Network ◽  
Induced Subgraphs ◽  
Topological Characterization ◽  
Network Information ◽  
The Subject ◽  
Euclidean Distances ◽  
The Brain

In this paper, we propose a graphlet-based topological algorithm for the investigation of the brain network at resting state (RS). To this aim, we model the brain as a graph, where (labeled) nodes correspond to specific cerebral areas and links are weighted connections determined by the intensity of the functional magnetic resonance imaging (fMRI). Then, we select a number of working graphlets, namely, connected and non-isomorphic induced subgraphs. We compute, for each labeled node, its Graphlet Degree Vector (GDV), which allows us to associate a GDV matrix to each one of the 133 subjects of the considered sample, reporting how many times each node of the atlas “touches” the independent orbits defined by the graphlet set. We focus on the 56 independent columns (i.e., non-redundant orbits) of the GDV matrices. By aggregating their count all over the 133 subjects and then by sorting each column independently, we obtain a sorted node table, whose top-level entries highlight the nodes (i.e., brain regions) most frequently touching each of the 56 independent graphlet orbits. Then, by pairwise comparing the columns of the sorted node table in the top-k entries for various values of k, we identify sets of nodes that are consistently involved with high frequency in the 56 independent graphlet orbits all over the 133 subjects. It turns out that these sets consist of labeled nodes directly belonging to the default mode network (DMN) or strongly interacting with it at the RS, indicating that graphlet analysis provides a viable tool for the topological characterization of such brain regions. We finally provide a validation of the graphlet approach by testing its power in catching network differences. To this aim, we encode in a Graphlet Correlation Matrix (GCM) the network information associated with each subject then construct a subject-to-subject Graphlet Correlation Distance (GCD) matrix based on the Euclidean distances between all possible pairs of GCM. The analysis of the clusters induced by the GCD matrix shows a clear separation of the subjects in two groups, whose relationship with the subject characteristics is investigated.

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