Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative stress and promoting myelination.

The taiep rat undergoes hypomyelination and progressive demyelination caused by an abnormal microtubule accumulation in oligodendrocytes, which elicits neuroinflammation and motor behavior dysfunction. Based on taurine antioxidant and proliferative actions, this work explored whether its sustained administration from the embryonic age to adulthood could prevent neuroinflammation, stimulate cell proliferation, promote myelination, and relieve motor impairment. Taurine (50 mg/L of drinking water = 50 ppm) was given to taiep pregnant rats on gestational day 15 and afterward to the male offspring until eight months of age. We measured the levels of nitric oxide (NO), malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), CXCL1, CXCR2 receptor, growth factors (BNDF and FGF2), cell proliferation, and myelin content over time. Integral motor behavior was also evaluated. Our results showed that taurine administration significantly decreased NO and MDA + 4-HDA levels, increased cell proliferation, and promoted myelination in an age- and brain region-dependent fashion compared with untreated taiep rats. Taurine effect on chemokines and growth factors was also variable. Taurine improved vestibular reflexes and limb muscular strength in perinatal rats and fine movements and immobility episodes in adult rats. These results show that chronic taurine administration partially alleviates the taiep neuropathology.

Smell facilitates auditory contagious yawning in stranger rats.

Most vertebrates yawn in situations ranging from relaxation to tension, but only humans and other primate species that show mental state attribution skills have been convincingly shown to display yawn contagion. Whether complex forms of empathy are necessary for yawn contagion to occur is still unclear. As empathy is a phylogenetically continuous trait, simple forms of empathy, such as emotional contagion, might be sufficient for non-primate species to show contagious yawning. In this study, we exposed pairs of male rats, which were selected for high yawning, with each other through a perforated wall and found that olfactory cues stimulated yawning, whereas visual cues inhibited it. Unexpectedly, cage-mate rats failed to show yawn contagion, although they did show correlated emotional reactivity. In contrast, stranger rats showed auditory contagious yawning and greater rates of smell-facilitated auditory contagious yawning, although they did not show correlated emotional reactivity. Strikingly, they did not show contagious yawning to rats from a low-yawning strain. These findings indicate that contagious yawning may be a widespread trait amongst vertebrates and that mechanisms other than empathy may be involved. We suggest that a communicatory function of yawning may be the mechanism responsible for yawn contagion in rats, as contagiousness was strain-specific and increased with olfactory cues, which are involved in mutual recognition.

Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

Effects of chronic taurine administration on healthy pregnant rats and the consequences on the offspring: Datasets for motor tests and oxidative stress.

We present the data for taurine (2-aminoethanesulfonic acid) treatment to healthy pregnant Sprague Dawley rats (SD). At embryonic day 15 (E15), healthy pregnant SD rats were given taurine treatment (50 mg/L drinking water) and then to their male offspring until they reached the age of eight months. We quantify, in the offspring, the concentration of nitric oxide (NO) through the Griess colorimetric reaction [1] and malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) by the Gérard-Monnier technique [2]. The assessment ages for NO and MDA + 4-HDA were at postnatal day 15 (PND15), 1, 3, and 8 months of age. The body weight was measured along with the integral motor behavior in the perinatal stage through the surface righting reflex test at PND5, cliff aversion test at PND9, grip strength test at PND 11, and front limb and hindlimb suspension tests at PND13. The tests were performed accordingly with [3]. The data obtained showed that SD rats with the taurine administration performed poorly in the motor tests compared with the untreated healthy rats. The taurine-treated rats also showed increased lipid peroxidation preferentially in cerebral regions involved in motor activity, such as the medulla oblongata, the subcortical nuclei, and the cerebral cortex. However, the taurine treatment only increased NO concentration in the evaluated cerebral regions at older ages. At E15, taurine plays a pivotal role in the excitatory/inhibitory neuromodulation, presumably by acting as an excitatory neurotransmitter during the GABA-switch [4]. The increase in the taurine concentration during the embryonic period might cause excitotoxicity in healthy brains, which might lead to impairments in the motor development of the offspring. Therefore, the present datasets can be valuable for researchers who attempt to use the taurine supplement on healthy animal models at gestational stages; and explore the relation with taurine intake during pregnancy in human patients. These datasets are related to the article "Long-term taurine administration improves motor skills in a tubulinopathy rat model by decreasing oxidative stress and promoting myelination" [5].

Comparative analysis of maternal care in the high-yawning (HY) and low-yawning (LY) sublines from Sprague-Dawley rats.

High- and low-yawning rats (HY and LY) were selectively bred as a function of their spontaneous yawning frequency with the LY subline about 2 yawns/hr and the HY 20 yawns/hr. The HY rats have more grooming bouts and travel longer distances in an open field. HY dams spent less time in the nest, retrieved their pups faster, and show a longer latency to licking and mouthing the pups than the LY or outbred Sprague-Dawley (SD) animals. The percentage of HY dams that had atypical retrieving was higher, with a lower nest quality, and produced offspring whose weights were lower than those from the LY subline. We also showed that the pregnant HY dams have fewer pups and the percentage that had lost at least three pups during lactation was higher than the SD and LY dams. In conclusion, HY dams are motivated to take care of their pups, but the "fine tuning" of maternal care is disturbed.

Yawning and Penile Erection Frequencies Are Resilient to Maternal Care Manipulation in the High-Yawning Subline of Sprague-Dawley Rats.

Yawning is a stereotyped behavioral pattern characterized by wide opening of the mouth associated with deep inspiration followed by short expiration. All vertebrate species yawn, but with low frequencies. We obtained two sublines of Sprague-Dawley (SD) rats by a strict inbreeding process: one with a high-yawning frequency (HY) of 20 yawns/h, which is one order of magnitude higher with respect to the low-yawning frequency (LY) subline, with 2 yawns/h. Outbred SD rats had a yawning frequency of 1 yawn/h. HY dams had a different organization of maternal care with respect to that displayed by LY and SD dams because HY dams constructed lower quality nests and had more re-retrieving and atypical retrieving. The aim of this study was to analyze the changes in maternal care using in- and cross-fostering between the sublines and SD dams and to measure spontaneous and dopaminergic-induced yawning, penile erections, grooming and scratching bouts. We also measured the expression of dopamine D2 receptors in the striatum using Western blot analysis. Our results showed that HY male rats reared by SD or LY dams did not significantly differ in yawning frequencies with respect to HY male rats reared by mothers of their own phenotype. Maternal care did not differ between sublines and SD dams independent of the litter they reared. However, LY rats reared by HY dams showed a significant increase in the number of spontaneous penile erections. Importantly, in-fostered HY male rats had the highest number of yawns induced by systemic administration of (-)-quinpirole supporting that higher maternal care display can influence the frequency of dopaminergic-induced yawning. In fact HY male rats in all conditions yawned more than did LY and SD male rats independent of the dam that raised them supporting a strong influence of genetic background. However SD male rats raised by LY dams showed significantly increased the dopamine D2 receptor expression. In conclusion, maternal care and the environmental nest conditions during the lactation period did not change the phenotypic characteristics of the yawning sublines supporting that their genetic background is fundamental for the expression of spontaneous or dopaminergic-induced yawning.

Genetic and littermate influences on yawning in two selectively bred strains of rats.

This study was made to separate genetic from postnatal maternal influences on yawning in two strains of Sprague-Dawley rats selected for high- (HY) and low-yawning frequency (LY). Foster mothers of the two strains reared litters of pups in the four possible combinations and yawning was recorded in a novel environment when the adult offspring were 75-day-old. Yawning frequency of males and females was affected by pup strain but not by the strain of the foster mothers, when litter size was made constant; HY adult offspring yawned more than LY adult offspring. Yawning frequency was higher in HY male offspring than in HY female offspring. An interaction term between pup sex and the strain of the foster mothers revealed that while males reared by LY mothers yawned more than males reared by HY mothers, females reared by HY mothers yawned more than females reared by LY mothers. Mean frequency of yawning increased with the sex ratio of HY litters. These findings indicate that genetic and genotype-correlated littermate effects influence yawning frequency of adult offspring in response to a novel environment.

Increased nitric oxide levels and nitric oxide synthase isoform expression in the cerebellum of the taiep rat during its severe demyelination stage.

We have previously reported progressive reactive astrocytes in the cerebellum of taiep rats, one of the most regions affected by demyelination, and activation of cerebellar glial cells in vitro. Based on the hypothesis that activated glial cells produce high levels of reactive nitrogen intermediates, we assessed the production of nitric oxide (NO) and the expression of the three NO synthases (NOS) in the cerebellum of 6-month-old taiep rats. A significant 40% increase of NO levels was measured in taiep rats when compared with controls. The protein and mRNA levels of the three NOS isoforms were also significantly increased. In contrast to controls, immunostaining assays against nNOS or iNOS showed an increased number of immunoreactive glial cells in the granular layer (nNOS) and Purkinje layer (iNOS) of cerebellum of taiep rats. Microglia-macrophages and both CD4- and CD8-immunoreactive cells were observed in cerebellar white matter of taiep rats only, thus suggesting other possible cell sources of those NOSs. Differences in the cellular location for eNOS immunoreactivity were not observed. The enhanced levels of NO, NOS proteins, mRNAs, and NOS immunoreactivities in glial cells and microglia strongly suggest glial activation together with the professional immune cells can aggravate the demyelination of aged taiep rats.

Analysis of chemokines and receptors expression profile in the myelin mutant taiep rat.

Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat.

Evidence in vitro of glial cell priming in the taiep rat.

Cultured glial cells from the cerebellum of 15-day-old taiep rats produced NO, increased iNOS levels, up-regulated iNOS expression and promoted TNF release when stimulated with LPS and IFNgamma. These responses were much greater than in control cells. In taiep glial cells, NO production and iNOS levels and expression induced by the co-stimulatory signal were resistant to the inhibitory effect of TGFbeta1. The glial cell priming might have been generated by oligodendrocyte alteration in taiep rats.

Subacute zinc administration and L-NAME caused an increase of NO, zinc, lipoperoxidation, and caspase-3 during a cerebral hypoxia-ischemia process in the rat.

Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc.