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.

Taste association capabilities differ in high- and low-yawning rats versus outbred Sprague-Dawley rats after prolonged sugar consumption.

Yawning is a stereotypical behavior pattern commonly associated with other behaviors such as grooming, sleepiness, and arousal. Several differences in behavioral and neurochemical characteristics have been described in high-yawning (HY) and low-yawning (LY) sublines from Sprague-Dawley (SD) rats that support they had changes in the neural mechanism between sublines. Differences in behavior and neurochemistry observed in yawning sublines could also overlap in processes needed during taste learning, particularly during conditioned taste aversion (CTA) and its latent inhibition. Therefore, the aim of this study was to analyze taste memory differences, after familiarization to novel or highly sweet stimuli, between yawning sublines and compare them with outbred SD rats. First, we evaluated changes in appetitive response during long-term sugar consumption for 14 days. Then, we evaluated the latent inhibition of CTA strength induced by this long pre-exposure, and we also measured aversive memory extinction rate. The results showed that SD rats and the two sublines developed similar CTA for novel sugar and significantly stronger appetitive memory after long-term sugar exposure. However, after 14 days of sugar exposure, HY and LY sublines were unable to develop latent inhibition of CTA after two acquisition trials and had a slower aversive memory extinction rate than outbreed rats. Thus, the inability of the HY and LY sublines to develop latent inhibition of CTA after long-term sugar exposure could be related to the time/context processes involved in long-term appetitive re-learning, and in the strong inbreeding that characterizes the behavioral traits of these sublines, suggesting that inbreeding affects associative learning, particularly after long-term exposure to sweet stimuli which reflects high familiarization.

Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities.

Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model.

Yawning reduces facial temperature in the high-yawning subline of Sprague-Dawley rats.

BACKGROUND: Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counterflow has been hypothesized as a mechanism for brain cooling. Studies have shown that yawns are strongly associated with physiological and pathological conditions that increase brain temperature, and that they are followed by equivalent decreases in brain temperature. However, measured reductions in cranial or facial temperatures following yawning have yet to be reported, to our knowledge. To accomplish this, we used a subline of Sprague-Dawley rats that yawn at a much greater rate (20 yawns/h) than do outbred Sprague-Dawley rats (2 yawns/h). RESULTS: Using an infrared camera, we effectively evaluated thermal changes in the cornea and concha of these rats before, during, and after yawns. The maximum temperature in both regions significantly decreased 10 s following yawns (concha: -0.3 °C, cornea: -0.4 °C), with a return to basal temperatures after 20 s. CONCLUSIONS: This study is the first clear demonstration of yawning-induced thermal cooling on the surface of the face, providing convergent evidence that this behavior plays a functional role in thermoregulation. As other studies have demonstrated that yawning is capable of reducing cortical brain temperature, our current data support the idea that yawning functions as a thermoregulator, affecting all structures within the head.

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.

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum.

The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

Label-Free Non-Linear Optics for the Study of Tubulin-Dependent Defects in Central Myelin.

The satisfactory visualization of cytoskeletal components in the brain is challenging. The ubiquitous distribution of the networks of microtubules, microfilaments, and intermediate filaments in all the neural tissues, together with the variability in the outcomes of fluorescent protein fusion strategies and their limited applicability to dynamic studies of antibodies and drugs as chromophore vehicles, make classical optical approaches not as effective as for other proteins. When tubulin needs to be studied, the label-free generation of second harmonics is a very suitable option due to the non-centrosymmetric organization of the molecule. This technique, when conjugated to microscopy, can qualitatively describe the volumetric distribution of parallel bundles of microtubules in biological samples, with the additional advantage of working with fresh tissues that are unfixed and unpermeabilized. This work describes how to image tubulin with a commercial second harmonic generation microscopy setup to highlight microtubules in the tubulin-enriched structures of the oligodendrocytes, as in hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) tubulinopathy, a recently described myelin disorder.

H-ABC tubulinopathy revealed by label-free second harmonic generation microscopy.

Hypomyelination with atrophy of the basal ganglia and cerebellum is a recently described tubulinopathy caused by a mutation in the tubulin beta 4a isoform, expressed in oligodendrocytes. The taiep rat is the only spontaneous tubulin beta 4a mutant available for the study of this pathology. We aimed to identify the effects of the tubulin mutation on freshly collected, unstained samples of the central white matter of taiep rats using second harmonic generation microscopy. Cytoskeletal differences between the central white matter of taiep rats and control animals were found. Nonlinear emissions from the processes and somata of oligodendrocytes in tubulin beta 4a mutant rats were consistently detected, in the shape of elongated structures and cell-like bodies, which were never detected in the controls. This signal represents the second harmonic trademark of the disease. The tissue was also fluorescently labeled and analyzed to corroborate the origin of the nonlinear signal. Besides enabling the description of structural and molecular aspects of H-ABC, our data open the door to the diagnostic use of nonlinear optics in the study of neurodegenerative diseases, with the additional advantage of a label-free approach that preserves tissue morphology and vitality.

Testicular androgens determining the incidence of spike-wave discharges in taiep rats: A model of H-ABC leukodystrophy.

Absence seizures are characterized as a generalized type of epilepsy that occurs during childhood. Importantly, absence seizures in children often discontinue after puberty. There is limited availability of animal models in which electroencephalography (EEG) can be performed in the long term; however, two absence seizure models, GAERS and WAG/Rij albino rats, are available. The taiep rat is a myelin mutant rat with tubulinopathy due to a tubulin ß 4A gene mutation and characteristic spike-wave discharges (SWDs) that mimic absence seizure epilepsy in humans and the above rat models. This study aimed to analyze spike-wave discharges after an orchiectomy was performed on postnatal day (PND) 2 or PND 90 in adult rats; and SWDs was recorded in both groups on PND 104. The results suggest that androgens play a critical role in susceptibility to SWDs. In fact, orchiectomy during the neonatal period significantly reduced the frequency of spike-wave discharges. However, if an orchiectomy was performed in adulthood, then SWDs were significantly increased. The mean duration of spike-wave discharges did not differ among the groups tested. Acute administration of testosterone (1 mg/kg) did not change the frequency or duration of spike-wave discharges in the control group or both orchiectomized groups. Overall, this study is the first to show a dichotomic influence of testicular androgens on spike-wave discharges. These findings will have implications in children with this type of generalized epilepsy and may explain the disappearance of absence epilepsy in two-thirds of patients after puberty.

Mating-induced analgesia is dependent of copulatory male pattern in high- and low- yawning male rats.

Mating behavior in rodents can modulate pain sensations in both sexes. In males, the execution of mounts, intromissions, and ejaculations induced a progressive increase in their vocalization thresholds induced by tail shocks and other types of noxious stimuli. We selectively inbred two sublines from Sprague-Dawley (SD) rats that differed in their spontaneous yawning frequency. The high-yawning (HY) subline had a mean of 20 yawns/h and a different pattern of sexual behavior characterized by longer interintromission intervals and more sexual bouts that delayed ejaculation. The low-yawning (LY) subline and SD rats yawned as a mean 2 and 1 yawns/h, respectively. So, we determine mating-induced analgesia in HY, LY, and SD male rats by measuring vocalization thresholds in response to noxious electric tail shocks. Our results showed that the magnitude of mating-induced analgesia was lower in HY and LY rats with respect to SD rats. When the rats performed different components of male sexual pattern, both sublines exhibited a significantly lower increase in their vocalization thresholds with respect to SD rats-being sublines less responsive regarding mating-induced analgesia. Pain modulation mechanisms depend on responses to stress, so the low levels of analgesia obtained in the yawning sublines may be due either to differences in their response to stress in other paradigms, or to atypical performance of male sexual behavior during mating, an event which as a stressful event in rats. Therefore, the yawning sublines are a suitable model for analyzing how a different temporal pattern in the display of male sexual behavior affects analgesia mechanisms. Our results concur with Wistar rats with different endophenotypes that could apply to humans as well.

Sex-specific hypothalamic expression of kisspeptin, gonadotropin releasing hormone, and kisspeptin receptor in progressive demyelination model.

Demyelinating diseases, such as multiple sclerosis, decrease the quality of life of patients and can affect reproduction. Assisted reproductive therapies are available, which although effective, aggravate motor symptoms. For this reason, it is important to determine how the control of the hypothalamus-pituitary-gonadal axis is affected in order to develop better strategies for these patients. One way to determine this is using animal models such as the taiep rat, which shows progressive demyelination of the central nervous system, and was used in the present study to characterize the expression of gonadotrophin-releasing hormone (GnRH), Kisspeptin, and kisspeptin receptor (Kiss1R) and luteinizing hormone (LH) secretion. The expression of kisspeptin, GnRH, and Kiss1R was determined at the hypothalamic level by immunofluorescence and serum LH levels were determined by ELISA. The expression of kisspeptin at the hypothalamic level showed sexual dimorphism, where there was an increase in males and a decrease in females during oestrus. There was no change in the expression of GnRH or kisspeptin receptor, regardless of sex. However, a decrease in serum LH concentration was observed in both sexes. The taiep rat showed changes in the expression of kisspeptin at the hypothalamic level. These changes are different from those reported in the literature with the use of animals with experimental allergic encephalomyelitis, this is because both animal models represent different degrees of progression of multiple sclerosis. Our results suggest that the effects on the hypothalamus-pituitary-gonadal axis depend on the differences between the demyelinating processes, their progression, and even individual factors, and it is thus important that fertility treatments are individualized to maximize therapeutic effects.

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.

Longitudinal Evaluation of Cerebellar Signs of H-ABC Tubulinopathy in a Patient and in the taiep Model.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a central neurodegenerative disease due to mutations in the tubulin beta-4A (TUBB4A) gene, characterized by motor development delay, abnormal movements, ataxia, spasticity, dysarthria, and cognitive deficits. Diagnosis is made by integrating clinical data and radiological signs. Differences in MRIs have been reported in patients that carry the same mutation; however, a quantitative study has not been performed so far. Our study aimed to provide a longitudinal analysis of the changes in the cerebellum (Cb), corpus callosum (CC), ventricular system, and striatum in a patient suffering from H-ABC and in the taiep rat. We correlated the MRI signs of the patient with the results of immunofluorescence, gait analysis, segmentation of cerebellum, CC, and ventricular system, performed in the taiep rat. We found that cerebellar and callosal changes, suggesting a potential hypomyelination, worsened with age, in concomitance with the emergence of ataxic gait. We also observed a progressive lateral ventriculomegaly in both patient and taiep, possibly secondary to the atrophy of the white matter. These white matter changes are progressive and can be involved in the clinical deterioration. Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) gives rise to a spectrum of clinical signs whose pathophysiology still needs to be understood.

Auditory impairment in H-ABC tubulinopathy.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H-ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H-ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II-IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H-ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies.

[Absence epilepsy models in rodents]. / Modelos de crisis de ausencia en roedores.

Animal models are a useful tool because it is possible to perform neuroanatomical, electrophysiological and pharmacological studies throughout their development. The most common models for experimental studies of absence seizures are the GAERS (Genetic Absence Epilepsy rat from Strasbourg) and the WAG/Rij (Wistar Absence Glaxo from Rijswik) rats. In WAG/RU rats it has been demonstrated that the perioral region in the somatosensorial cortex shows a zone with hyperexcitability which is the origin of spike wave discharges (SWD). In fact, this cortical area shows modifications in sodium channels which increase the excitability of cortical neurons; for this reason, local application of phenytoin or lidocaine, which block sodium channels, reduce SWD. Ethosuximide decreases and pentylenetetrazol increases SWD in GAERS and WAG/Rij rats. At the Institute of Physiology in the Benemérita Autonomous University of Puebla we have obtained a myelin mutant rat called "taiep", which is the acronym of tremor, ataxia, immobility episodes, epilepsy, and paralysis. This model shows a SWD with higher frequency during awaking periods; the SWD increases with systemic administration of pentylenetetrazol and decreases with ethosuximide. All these findings in animal models are susceptible to be tested in human beings through magneto- and electro-encephalographic recording techniques to discern the source of this type of epilepsy. Thus, in biomedical research, animal models are useful tools to discern the neural and network alterations responsible for the absence seizures, and allow to design of more specific therapeutic options with fewer side effects.

[The myelin mutant taiep as a model for abscence crisis]. / El mutante de mielina taiep como un modelo de crisis de ausencia.

BACKGROUND: Taiep rat is a myelin mutant rat with hypomyelination followed by progressive demyelination. This mutant presents cortical discharges with a spindle form, with an ascending and descending phases similar to absence epilepsy. METHODS: Taiep rats were maintained under standard animal room conditions with free access to balanced rodent pellets and tap water. Rats were anesthetized with chloral hydrate under aseptic conditions; three stainless steel screws and a bipolar electrode were implanted in the hippocampus. The signals were amplified, filtered and recorded using a video-EEG Harmonie system (Canada). All data were analyzed using Sensa and Luna modules. RESULTS: Our results showed that taiep rats have spike-wave discharges (SWD) during wake, slow wake sleep (SWS) and rapid eye movement (REM), being statistically higher and longer during awake period than SWS or REM sleep. The systemic administration of pilocarpine, a cholinergic agonist, increased dramatically the cortical discharges with five characteristic seizures patterns and concomitantly decreased the frequency and duration of absence crisis. However, only 80% of the taiep rats tested showed this paroxysm. On the other hand, 100% of control Sprague-Dawley rats showed tonic clonic seizures, indicating some type of resistance to this muscarinic cholinergic drug in taiep rats. CONCLUSIONS: These results showed that the taiep rat, a myelin mutant, is a good model for the electrophysiological and pharmacological study of absence epilepsy, particularly considering its resistance to pilocarpine-induced seizures.

Brain Processing of Complex Geometric Forms in a Visual Memory Task Increases P2 Amplitude.

We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain's processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological modality. We use complex geometric polygons to assess visual working memory in a modified change detection task. Three different types of backgrounds were used to manipulate memory loading and 18 complex geometric polygons to manipulate stimuli configuration. The goal of our study was to test whether the memory load and configuration affect the correct-recall ratios. We expected that increasing visual items loading and changing configuration of items would induce differences in working memory performance. Brain activity related to the task was assessed through event-related potentials (ERP), during the test phase of each trial. Our results showed that visual items loading and changing of item configuration affect working memory on test phase on ERP component P2, but does not affect performance. However frontal related ERP component-P3-was minimally affected by visual memory loading or configuration changing, supporting that working memory is related to a filtering processing in posterior brain regions.

MRI Features in a Rat Model of H-ABC Tubulinopathy.

Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.