Albino people are known to have vision deficit. Albino animals are shown to have abnormal connectivity and malformation of the visual system. However, not many studies have revealed visual impairment ...of albino animals in the level of perception. To link anatomical abnormality and perceptual visual impairment of albinism, we compared the perceptual vision between the pigmented Long-Evans and the albino Wistar rats. We used the slow angled-descent forepaw grasping (SLAG) test. We hanged the rats in the air by their tails and slowly moved them around a safety bar so that they could see it. When the rats recognized the bar and try to grab it to escape, we counted the trial as 'positive', and we measured positive rates. We also measured the distance between the bar and their whiskers during the rats' initial grasping action, and evaluated type of action at the first contact to the bar. The positive-action rate in the Long-Evans rat group showed significantly higher than the Wistar rat group (0.85 ± 0.047, n = 10, vs. 0.29 ± 0.043, n = 10; P < 0.0001). Besides, when the action was positive, the distance between the bar and their whiskers was longer in the Long-Evans rat group than that in the Wistar rat group (117 ± 5.3 mm vs. 58.8 ± 4.6 mm; P < 0.0001). The Long-Evans rats grasped the bar more precisely than the Wistar rats. The pigmented Long-Evans rats have much better visual perception than the albino Wistar rats.
Wistar Kyoto (WKY) rats manifest abnormalities in the function of monoamine receptors and transporters, as well as levels of these neurotransmitters in the brain. The present study assessed ...alterations in the firing activity of serotonin (5-hydroxytryptamine 5-HT), norepinephrine (NE), and dopamine (DA) neurons, as well as the activity of 5-HT and NE receptors and transporters in the hippocampus.
In vivo electrophysiological recordings were conducted in male WKY and Wistar rats. Extracellular single-unit recordings of 5-HT, NE, and DA neurons were performed. Recordings of pyramidal neurons were conducted in the medial prefrontal cortex (mPFC) and the hippocampus, where direct application of 5-HT and NE by iontophoresis was also carried out.
The mean firing rate of 5-HT neurons was significantly decreased in WKY compared to Wistar rats. The burst activity of NE neurons was significantly increased in WKY, while their mean firing activity was not changed. There was no alteration in the firing, burst, and population activity of DA neurons in WKY animals. In the hippocampus, a decrease in sensitivity of α
-adrenoceptors, but not 5-HT receptors, was observed. There was, however, no change in the activity of 5-HT and NE transporters. The firing activity of mPFC pyramidal neurons was similar in WKY versus Wistar rats.
In WKY rats, there was a decrease in the firing activity of 5-HT neurons. There was also an enhanced burst activity of NE neurons, accompanied by a reduction in sensitivity of the α
-adrenoceptor in the hippocampus, inferring a decrease in NE transmission.
Many researchers assume that laboratory rats have poor vision, and accordingly, that they need not consider differences in the visual function of rats as a consequence of strain or experience. ...Currently, it is not specifically known whether rat domestication has negatively affected the visual function of laboratory rat strains, what the effects of strain albinism are on rat visual function, or whether there are strain differences in the visual function of laboratory rats that are independent of pigmentation. In order to address these questions, we measured psychophysically the vertical grating acuity of three pigmented (Dark Agouti, Fisher–Norway, Long-Evans) and three albino (Fisher-344, Sprague–Dawley, Wistar) strains of laboratory rats, and compared their acuity with that of wild rats. The grating thresholds of Dark Agouti, Long-Evans and wild strains clustered around 1.0 cycle/degree (c/d) and did not significantly differ from one another. Fisher–Norway rats, however, had a significantly higher threshold of 1.5 c/d. The grating thresholds of Fisher-344, Sprague–Dawley, and Wistar strains, which were clustered around 0.5 c/d, were significantly lower than those of the pigmented strains. These data demonstrate that there is significant strain variability in the visual function of laboratory rats. Domestication of Long-Evans and Dark Agouti strains does not appear to have compromised visual acuity, but in the case of Fisher–Norway rats, selective breeding may have enhanced their acuity. Strain selection associated with albinism, however, appears to have consistently impaired visual acuity. Therefore, a consideration of strain differences in visual function should accompany the selection of a rat model for behavioral tasks that involve vision, or when comparing visuo-behavioral measurements across rat strains.
The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetic model for cerebral stroke. Although a recent study on a congenic SHRSP suggested that a nonsense mutation in stromal interaction ...molecule 1 ( Stim1 ) encoding a major component of store-operated Ca 2+ entry was a causal variant for stroke in SHRSP, this was not conclusive because the congenic region including Stim1 in that rat was too wide. On the other hand, we demonstrated that the Wistar-Kyoto (WKY)-derived congenic fragment adjacent to Stim1 exacerbated stroke susceptibility in a congenic SHRSP called SPwch1.71. In the present study, we directly examined the effects of the Stim1 genotype on stroke susceptibility using SHRSP in which wild-type Stim1 was knocked in (called Stim1 -KI SHRSP). The combined effects of Stim1 and the congenic fragment of SPwch1.71 were also investigated.
Stroke susceptibility was assessed by the stroke symptom-free and survival periods based on observations of behavioral symptoms and reductions in body weight.
Stim1 -KI SHRSP was more resistant to, while SPwch1.71 was more susceptible to stroke than the original SHRSP. Introgression of the wild-type Stim1 of Stim1 -KI SHRSP into SPwch1.71 by the generation of F1 rats ameliorated stroke susceptibility in SPwch1.71. Gene expression, whole-genome sequencing, and biochemical analyses identified Art2b , Folr1 , and Pde2a as possible candidate genes accelerating stroke in SPwch1.71.
The substitution of SHRSP-type Stim1 to wild-type Stim1 ameliorated stroke susceptibility in both SHRSP and SPwch1.71, indicating that the nonsense mutation in Stim1 is causally related to stroke susceptibility in SHRSP.
Stimulation of the mesencephalic locomotor region elicits exaggerated sympathetic nerve and pressor responses in spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto rats ...(WKY). This suggests that central command or its influence on vasomotor centers is augmented in hypertension. The decerebrate animal model possesses an ability to evoke intermittent bouts of spontaneously occurring motor activity (SpMA) and generates cardiovascular responses associated with the SpMA. It remains unknown whether the changes in sympathetic nerve activity and hemodynamics during SpMA are altered by hypertension. To test the hypothesis that the responses in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) during SpMA are exaggerated with hypertension, this study aimed to compare the responses in decerebrate, paralyzed SHR, WKY, and normotensive Sprague-Dawley (SD) rats. In all strains, an abrupt increase in RSNA occurred in synchronization with tibial motor discharge (an index of motor activity) and was followed by rises in MAP and heart rate. The centrally evoked increase in RSNA and MAP during SpMA was much greater (306 ± 110%) in SHR than WKY (187 ± 146%) and SD (165 ± 44%). Although resting baroreflex-mediated changes in RSNA were not different across strains, mechanically or pharmacologically induced elevations in MAP attenuated or abolished the RSNA increase during SpMA in WKY and SD but had no effect in SHR. It is likely that the exaggerated sympathetic nerve and pressor responses during SpMA in SHR are induced along a central command pathway independent of the arterial baroreflex and/or result from central command-induced inhibition of the baroreflex.
Abstract We previously reported that Wistar Kyoto rats, an animal model of depression, have a characteristically abnormal serine metabolism in the brain, i.e., lower serine and cystathionine, which ...is a metabolite of serine, concentrations in the brain. To explore the mechanism underlying this abnormality, the expression of cystathionine β-synthase and serine racemase, which are the enzymes involved in the serine metabolism, was investigated in the cerebellum and hippocampus of Wistar and Wistar Kyoto rats. Wistar Kyoto rats exhibited a significantly lower mRNA expression of cystathionine β-synthase in the cerebellum in comparison with Wistar rats, while expression levels in the hippocampus did not differ between strains. Previous study indicated that the reduction of cystathionine β-synthase in the brain induced cerebellar aplasia in mice. Therefore, the cerebellar size was compared between Wistar rats and Wistar Kyoto rats. Wistar Kyoto rats displayed a lower ratio of cerebellum weight to whole-brain weight compared with Wistar rats of the same generation or similar body weight, suggesting that Wistar Kyoto rats exhibit smaller cerebellum. These results suggest that the lower mRNA expression of cystathionine β-synthase in the cerebellum and the smaller size of cerebellum may be related to the depression-like behavior in Wistar Kyoto rats.
Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more ...comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies.
Individual differences in reward-related learning are relevant to many behavioral disorders. Sensory cues that predict reward can become incentive stimuli that adaptively support behavior, or ...alternatively, cause maladaptive behaviors. The spontaneously hypertensive rat (SHR) expresses a genetically determined elevated sensitivity to delay of reward, and has been extensively studied as a behavioral model for attention deficit hyperactivity disorder (ADHD). We investigated reward-related learning in the SHR, comparing them to Sprague-Dawley (SD) rats as a reference strain. A standard Pavlovian conditioned approach task was used, in which a lever cue was followed by reward. Lever presses could occur while the lever was extended, but had no effect on reward delivery. The behavior of both the SHRs and the SD rats showed that they learnt that the lever cue predicted reward. However, the pattern of behavior differed between the strains. During lever cue presentation, SD rats pressed the lever more often and made fewer magazine entries than SHRs. When lever contacts that did not result in lever presses were analyzed, there was no significant difference between SHRs and SDs. These results suggest that the SHRs attributed less incentive value to the conditioned stimulus than the SD rats. During the presentation of the conditioned cue, cue directed responses are called sign tracking responses, whereas responses directed towards the food magazine are called goal tracking responses. Analysis of behavior using a standard Pavlovian conditioned approach index to quantify sign and goal tracking tendencies showed that both strains had a tendency towards goal tracking in this task. However, the SHRs showed a significantly greater goal tracking tendency than the SD rats. Taken together, these findings suggest that attribution of incentive value to reward predicting cues is attenuated in SHRs, which might explain their elevated sensitivity to delay of reward.
Abstract
Environmental bisphenol compounds like bisphenol F (BPF) are endocrine-disrupting chemicals (EDCs) affecting adipose and classical endocrine systems. Genetic factors that influence EDC ...exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH heterogeneous stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/l in 0.1% EtOH for 10 weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggest that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.
•Compared behavioural and the volume of associated brain areas in male and female LER and WR rats.•LER and WR developed skilled reaching behaviour at different rates.•LER outperformed WR on tasks ...related to spatial and contextual learning.•Males excelled in spatial learning and females excelled in contextual learning in the LER strain.•Larger volume of associated brain areas did not always confer enhanced behaviour.
Alterations in behaviour can arise through a number of factors, including strain and sex. Here, we explored strain and sex differences between Long–Evans (LER) and Wistar (WR) male and female rats that had been trained in a myriad of behavioural tasks. Tests included those assessing motor learning (skilled reaching task), spatial learning and memory (Morris water task), contextual learning (discriminative fear-conditioning to context) and anxiety behaviour (elevated plus maze). Following behavioural assessment, associated brain areas were examined for volumetric differences, including the hippocampus and its subregions, prefrontal cortex areas and the amygdala. LER and WR differed in their rates of performance in the skilled reaching task throughout the training period. Overall, LER outperformed WR in tasks related to contextual and spatial learning, although this was not accompanied by larger volumes of associated brain areas. Males outperformed females in spatial learning, and females outperformed males in the contextual fear-conditioning task and had an associated larger amygdalar volume, although these sexual dimorphisms were only observed within the LER strain. Overall, this study highlights differences between these two rat strains as well as highlights that larger volumetric estimates of brain areas do not always confer improved function of associated behaviours.
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