scholarly journals Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task

2018 ◽  
Author(s):  
Laura E. Berkowitz ◽  
Ryan E. Harvey ◽  
Emma Drake ◽  
Shannon M. Thompson ◽  
Benjamin J. Clark

AbstractSpatial navigation is impaired in early stages of Alzheimer’s disease (AD), and may be a defining behavioral marker of preclinical AD. Nevertheless, limitations of diagnostic criteria for AD and within animal models of AD make characterization of preclinical AD difficult. A new rat model (TgF344-AD) of AD overcomes many of these limitations, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n=16) and Fischer 344 (n=12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4-5 and 7-8 months of age, with deficits in the hidden platform task emerging at 10-11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and a wider search area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable deficits to those found in individuals in the early stages of AD.

Author(s):  
D.R. Mattie ◽  
J.J. Maslanka ◽  
C.D. Flemming

Halocarbon 27-S (H 27-S) is a polymer of chlorotrifluoroethylene (CTFE). Since metabolism of CTFE yields inorganic fluoride, it was believed that H 27-S would also yield fluoride in the blood. Exposure to fluorine results in deposition in bone as calcium fluoride or fluorapatite. Deposition of fluoride in the bone matrix should result in an altered calcium phosphorus ratio (CaP). The objective of this study was to determine the CaP of femurs of male and female rats exposed subchronically to H 27-S using energy dispersive x-ray analysis techniques and to compare CaP from exposed rats with the CaP of control rats.Male and female rats were dosed daily with 2.5 g H 27-S/kg body weight by gavage for 7 or 21 days. Rats were sacrificed at 7, 21 and 35 days (14 days after the 21 day dosing). Femurs of three rats of each sex and each group were analyzed.


2005 ◽  
Vol 180 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Russell W. Brown ◽  
Kimberly N. Thompson ◽  
Ivy A. Click ◽  
Razaria A. C. Best ◽  
Stephanie K. Thacker ◽  
...  

2021 ◽  
pp. 019262332110536
Author(s):  
Debra A. Tokarz ◽  
Margarita M. Gruebbel ◽  
Gabrielle A. Willson ◽  
Jerry F. Hardisty ◽  
Gail Pearse ◽  
...  

Spontaneous primary pleural mesotheliomas in Fischer 344 (F344) or other rat strains have rarely been reported. The objectives of this retrospective study were to develop historical incidence data and better characterize the light-microscopic morphology of these naturally occurring neoplasms in a large cohort of rats of several strains. A retrospective review was performed of National Toxicology Program (NTP) studies in rats conducted between 1980 and 2019 and comprising a total of 104,029 rats (51,326 males, 52,703 females), predominantly (90%) of the F344 strain. Of the 94,062 F344 rats surveyed, there were 30 cases of primary pleural mesotheliomas (22 males, 8 females). Of the 2998 Wistar Han rats surveyed, primary pleural mesotheliomas were present in 2 male rats. No primary pleural mesotheliomas were noted in male and female rats of other strains (6669 Sprague Dawley; 300 Osborne-Mendel). All primary pleural mesotheliomas in control and treated F344 and Wistar Han rats were considered spontaneous and unrelated to treatment. Based on light-microscopic evaluation of paraffin-embedded hematoxylin and eosin stained sections, only epithelioid and biphasic histologic subtypes were observed: 18 and 12 in F344 rats, respectively, and one each in Wistar Han rats. No sarcomatoid subtype cases were noted in any strain of rat.


1993 ◽  
Vol 12 (4) ◽  
pp. 359-367
Author(s):  
Carlton D. Jackson ◽  
Gerald M. Cronin ◽  
Richard J. Brown

Triprolidine, used extensively as an antihistamine, was studied for subchronic toxicity by administration as an admixture in the diet to male and female Fischer 344 rats at dosage levels of 0, 156, 312, 625, 1250, and 2500 parts per million (ppm) for 14 days and in a second study at 0, 250, 500, 1000, 2000, and 4000 ppm for 90 days. In the 14-day study, the only sign of toxicity observed either clinically or histologically was a reduction of final body weights (less than 10%) of both male and female rats in the 2500 ppm dosage group associated with reduced food consumption. In the 90-day study, final body weights were reduced, compared to controls, at the higher dosage levels with 4000 ppm resulting in a 20% and 13.4% reduction in males and females, respectively. Target organs were identified as the liver with hepatic fatty change and the parotid salivary gland, which exhibited treatment-related cytoplasmic alterations of the acinar cells. Males were more susceptible than females to both of these effects. These results indicate that rats would tolerate 2000 ppm triprolidine in a 2-year chronic bioassay without significant shortening of life span.


Author(s):  
D.R. Mattie ◽  
M.R. Chase ◽  
E.R. Kinkead ◽  
R.E. Whitmire

Chlorotrifluoroethylene (CTFE) oligomer is a nonflammable, saturated, hydrogen-free halocarbon oil with chain lengths of six to ten carbons. CTFE was seen to have a low degree of toxicity in acute toxicity tests. A subchronic study was conducted because CTFE is an excellent candidate hydraulic fluid. The objective of this electron microscopic investigation was to examine and compare the livers of male and female rats after inhalation exposure to CTFE for 90 days.Male and female Fischer-344 rats were exposed to 0.25, 0.5, or 1.0 mg/L CTFE aerosol for 90 days, 6 h/day, 5 days/week. An equal number of control rats were exposed to air only. Following the 90-day exposure period, 10 male and 10 female rats were sacrificed from each group. A 1mm slice of the left lobe of the liver of three rats of each sex and each group was collected for transmission electron microscopic examination.


1998 ◽  
Vol 41 (4) ◽  
pp. 167-173 ◽  
Author(s):  
Vladimír Bláha ◽  
Zhong-jin Yang ◽  
Michael Meguid ◽  
Jia-ke Chai ◽  
Zdeněk Zadák

The appetite suppressing effect of tobacco products, via the main pharmacological agent nicotine, is a major reason for its usage both by woman and man. Food intake (FI) could be changed by altering either meal size (MZ) or meal number (MN), which are regulated dependently in a reciprocal manner. The present study investigated the effect of systemic nicotine administration on the rat feeding pattern. Because of gender differences in the effects of nicotine, both male and female rats were studied. Alzet mini-osmotic pumps (Model 2001) and the automated rat eatometer were used to evaluate the feeding pattern of male and female Fischer 344 rats during seven days of systemic nicotine infusion (6 mg/kg b.w. s.c.). The main findings are: 1) systemic nicotine infusion decreased food intake in both sexes; 2) the decreased food intake was due to significantly reduced meal sizes while meal numbers were not altered significantly in either males or females; 3) the cyclical pattern of vaginal smears, food intake, meal number and meal size of female rats was not affected by nicotine administration. We conclude that the feeding suppressive effect of nicotine, which is due to reduced meal sizes and thus satiation, is not sex-hormones related.


1997 ◽  
Vol 16 (6) ◽  
pp. 639-657 ◽  
Author(s):  
J. L. Zimmermann ◽  
L. L. Truex

The monocomponent insulin analog LY275585 was administered to Fischer 344 rats in daily subcutaneous doses of 0, 20, or 200 U/kg for 12 months. Each treatment group consisted of 30 males and 30 females, and the vehicle control group consisted of 35 of each sex. Changes related to the pharmacologic activity of LY275585 included an increase in body weight, body weight gain, food consumption, and efficacy of food utilization in male and female rats given 200 U/kg. Pharmacologically related clinical chemistry effects occurring at 200 U/kg were an increase in mean serum glucose (24 h postdose) of males and females, a slight decrease in mean serum triglyceride of females, and decreased mean serum cholesterol of males and females. Fewer effects occurred in low-dose rats (20 U/kg) and included an increase of efficiency of food utilization only in female rats, a slight decrease in mean serum triglyceride in females, and decreased mean serum cholesterol in low-dose males and females. Three male and two female rats administered 200 U/kg died during the treatment period. Death of one male was attributed to hypoglycemia. Cause of death of four other high-dose rats was either not apparent, or the result of a variety of intercurrent disease processes unrelated to treatment. Survival in the low-dose (20 U/kg) and control groups was similar; one rat in each group died prior to treatment termination. The only compound-related lesion associated with treatment was a non-dose-related enhancement of the degree and incidence of inflammation at the site of subcutaneous injection. There were no compound-related changes in background lesions including neoplasms, or in hematologic or urinalysis values. In a comparison study, pharmacokinetic profiles of LY275585 and serum glucose values were determined in groups of 30 male and female rats administered single doses of 20 or 200 U/kg. Plasma levels of LY275585 peaked after 30 min, were dose related, and were similar in male and female rats. The hypoglycemia produced in rats receiving a single dose of 20 U/kg was maximal, suggesting saturation of the insulin receptor sites at this dose. The dose of 200 U/kg of LY275585 was, therefore, a supramaximal pharmacological dose when compared to an average daily human dose of 0.5 U/kg/ d. It is concluded that no toxicologically significant changes, other than moderate injection site inflammation, occurred in Fischer 344 rats treated with LY275585 at doses of 20 and 200 U/kg for 12 months.


2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.


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