The presence of VEGF and Notch2 during preantral-antral follicular transition in infantile rats: Anatomical evidence and its implications.

Folliculogenesis is a process that depends on angiogenesis, in which VEGF and Notch signaling pathway members are involved. Although this pathway is present in preantral and antral follicular structures during the second stage of folliculogenesis, this association has not been described. Therefore, this study aimed to identify VEGF and Notch2 in ovary structures of infantile rats after induction of follicular development with a gonadotropin stimulus. In order to explore this possibility we analyzed rat ovary morphology from days 10-25 after birth; subsequently, the transition from preantral follicle to an antral stage was analyzed by the induction of follicular development with equine chorionic gonadotropin (eCG) and VEGF and Notch were identified in the rat ovary by fluorescence. The histological analysis revealed that the ovary of a 10-day-old rat has the highest percentage of preantral follicles and based on this a 10IU eCG dose promoted an increase in the number of antral follicles, as well as a decrease in the number of preantral follicles, related to which there was an increase in ovary weight and size. In addition, a higher concentration of circulating estradiol was observed, proliferation of granulosa cells in both follicle groups was stimulated, and the accumulation of VEGF in granulosa and theca cells and in the antral follicle oocyte was increased (p<0.05), whereas the presence of Notch2 was limited to mural granulosa cells, in granulosa cells that formed the cumulus oophorus and in the oocyte of both groups of follicles. The multiple correspondence analysis allowed us to support an association between VEGF and Notch2 during the transition from preantral to antral follicles in the ovary of an infantile rat.

Self-regulation of eating and physical activity is lower in obese female college students as compared to their normal weight counterparts.

OBJECTIVE: Obesity is characterized, among other features, by overeating, reduced physical activity and an abnormal accumulation of body fat. These features are thought to result, at least in part, from the individual's inability to self-regulate their eating and physical activity behaviors (E&PaB). Self-regulation of the E&PaB is a three-step sequential process: self-observation, self-evaluation and self-reaction. However, it is yet unclear whether deficient self-regulation of E&PaB could predispose, facilitate and/or consolidate obesity. Unraveling this issue is fundamental in order to more precisely define the role of self-regulation of E&PaB in the management of obesity. METHODS: This research was focused on the question of whether or not self-regulation of E&PaB is related to obesity in female undergraduate students. This population segment seems especially vulnerable to developing obesity since they undergo a significant shift of their E&PaB upon their university enrollment. To address this question, a cross-sectional study with 108 female undergraduate students with normal weight (n = 80) or obesity (n = 28) was performed, in which self-regulation of eating habits and physical activity was measured by two validated scales and a personal data questionnaire. RESULTS: Female undergraduate students displaying lower E&PaB self-reactions were consistently overweight or obese. In addition, a multivariate analysis identified high levels of self-reaction towards eating habits related to a minor presence of overweight issues or obesity. CONCLUSION: Self-regulation should be an essential component in the strategies for obesity prevention as an integral approach that must include orientation about healthy eating and physical activity behaviors. In addition, further studies on the effect of self-regulation in the treatment of the obesity are needed.

Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains.

Neuroendocrine cells are present in the domestic fowl ovary.

Neuroendocrine cells are present in virtually all organs of the vertebrate body; however, it is yet uncertain whether they exist in the ovaries. Previous reports of ovarian neurons and neuron-like cells in mammals and birds might have resulted from misidentification. The aim of the present work was to determine the identity of neuron-like cells in immature ovaries of the domestic fowl. Cells immunoreactive to neurofilaments, synaptophysin, and chromogranin-A, with small, dense-core secretory granules, were consistently observed throughout the sub-cortical ovarian medulla and cortical interfollicular stroma. These cells also displayed immunoreactivity for tyrosine, tryptophan and dopamine ß-hydroxylases, as well as to aromatic L-DOPA decarboxylase, implying their ability to synthesize both catecholamines and indolamines. Our results support the argument that the ovarian cells previously reported as neuron-like in birds, are neuroendocrine cells.

Looking beyond Self-Protection: The Eyes Instruct Systemic Immune Tolerance Early in Life.

The eyes provide themselves with immune tolerance. Frequent skin inflammatory diseases in young blind people suggest, nonetheless, that the eyes instruct a systemic immune tolerance that benefits the whole body. We tested this premise by using delayed skin contact hypersensitivity (DSCH) as a tool to compare the inflammatory response developed by sighted (S) and birth-enucleated (BE) mice against oxazolone or dinitrofluorobenzene at the ages of 10, 30 and 60 days of life. Adult mice enucleated (AE) at 60 days of age were also assessed when they reached 120 days of life. BE mice displayed exacerbated DSCH at 60 but not at 10 or 30 days of age. AE mice, in contrast, show no exacerbated DSCH. Skin inflammation in 60-day-old BE mice was hapten exclusive and supported by distinct CD8+ lymphocytes. The number of intraepidermal T lymphocytes and migrating Langerhans cells was, however, similar between S and BE mice by the age of 60 days. Our observations support the idea that the eyes instruct systemic immune tolerance that benefits organs outside the eyes from an early age. The higher prevalence of inflammatory skin disorders reported in young people might then reflect reduced immune tolerance associated with the impaired functional morphology of the eyes.

Imipramine Administration in Brucella abortus 2308-Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count.

Brucellosis infection causes non-specific symptoms such as fever, chills, sweating, headaches, myalgia, arthralgia, anorexia, fatigue, and mood disorders. In mouse models, it has been associated with increased levels of IL-6, TNF-α, and IFN-γ, a decrease in serotonin and dopamine levels within the hippocampus, induced loss of muscle strength and equilibrium, and increased anxiety and hopelessness. Imipramine (ImiP), a tricyclic antidepressant, is used to alleviate neuropathic pain. This study evaluated the effects of ImiP on Balb/c mice infected with Brucella abortus 2308 (Ba) at 14- and 28-days post-infection. Serum levels of six cytokines (IFN-γ, IL-6, TNF-α, IL-12, MCP-1. and IL-10) were assessed by FACS, while the number of bacteria in the spleen was measured via CFU. Serotonin levels in the hippocampus were analyzed via HPLC, and behavioral tests were conducted to assess strength, equilibrium, and mood. Our results showed that mice infected with Brucella abortus 2308 and treated with ImiP for six days (Im6Ba14) had significantly different outcomes compared to infected mice (Ba14) at day 14 post-infection. The mood was enhanced in the forced swimming test (FST) (p < 0.01), tail suspension test (TST) (p < 0.0001), and open-field test (p < 0.0001). Additionally, there was an increase in serotonin levels in the hippocampus (p < 0.001). Furthermore, there was an improvement in equilibrium (p < 0.0001) and muscle strength (p < 0.01). Lastly, there was a decrease in IL-6 levels (p < 0.05) and CFU count in the spleen (p < 0.0001). At 28 days, infected mice that received ImiP for 20 days (Im20Ba28) showed preservation of positive effects compared to infected mice (Ba28). These effects include the following: (1) improved FST (p < 0.0001) and TST (p < 0.0001); (2) better equilibrium (p < 0.0001) and muscle strength (p < 0.0001); (3) decreased IL-6 levels (p < 0.05); and (4) reduced CFU count in the spleen (p < 0.0001). These findings suggest the potential for ImiP to be used as an adjuvant treatment for the symptoms of brucellosis, which requires future studies.

Psychological suppressive profile and autoantibodies variability in women living with breast cancer: A prospective cross-sectional study.

Breast cancer (BC) is a leading cause of women's morbimortality worldwide. Unfortunately, attempts to predict women's susceptibility to developing BC well before it becomes symptomatic, based on their genetic, family, and reproductive background have proved unsatisfactory. Here we analyze the matching of personality traits and protein serum profiles to predict women's susceptibility to developing cancer. We conducted a prospective study among 150 women (aged 18-70 years), who were distributed into three groups (n = 50): women without breast pathology and women diagnosed with BC or benign breast pathology. Psychological data were obtained through standardized psychological tests and serum protein samples were analyzed through semiquantitative protein immunoblotting. The matching for psychological and immunological profiles was constructed from these data using a mathematical generalized linear model.The model predicted that women who have stronger associations between high-intensity stress responses, emotional containment, and an increased number and reduced variability of serum proteins (detected by IgG autoantibodies) have the greatest susceptibility to develop BC before the disease has manifested clinically. Hence, the present study endorses the possibility of using psychological and biochemical tests in combination to increase the possibility of identifying women at risk of developing BC before the disease shows clinical manifestations. A longitudinal study must be instrumented to test the prediction ability of the instrument in real scenarios. Trial registration: Committee of Ethical Research of the Hospital General de México "Dr. Eduardo Liceaga," Ministry of Health (DI/12/111/03/064).

Expression of Claudin-4 in Lung Ischemia-Reperfusion Injury in Experimental Lung Transplantation.

OBJECTIVE: To assess the presence of CLDN4 in bronchoalveolar lavage fluid (BALF) and pulmonary tissue as an early indicator of LIRI and its relationship with changes in pulmonary physiology, edema formation and histology in an experimental porcine model of LTx with CIT of 50 min or 6 h. METHODS: In 12 pigs, LIRI was produced by: group I (n = 6) LTx with 50 min of CIT (LTx-50 min-CIT); and group II (n = 6) LTx with 6 h of CIT (LTx-6h-CIT). The lung function, edema formation, macroscopic and microscopic changes were assessed. CLDN4 expression in BALF and pulmonary tissue were determined. RESULTS: Both groups presented similar clinical, edema, and histological damage, as well as similar expression of CLDN4 in BALF and tissue (p > 0.05, RM-ANOVA). CONCLUSION: CLDN4 expressed in BALF and the pulmonary tissue during the first 5 h within 72 h of the PGD window are not associated by the deterioration of lung function, edema and lung histological injury, in LTx with CIT 50 min or 6 h, CLDN4 does not seem to be a valuable indicator of LIRI.

Late onset muscle plasticity in the whisker pad of enucleated rats.

Blindness leads to a major reorganization of neural pathways associated with touch. Because incoming somatosensory information influences motor output, it is plausible that motor plasticity occurs in the blind. In this work, we evaluated this issue at the peripheral level in enucleated rats. Whisker muscles in enucleated rats 160 days of age or older showed increased cytochrome oxidase activity, capillary density, motor plate size, and amplitude of evoked field potentials as compared with their control counterparts. Such differences were not observed at ages 10 and 60 days, the capillary density was the exception being greater in the enucleated rat at the latter age. Interestingly, there was a trend to increased neurotrophin-3 concentrations in the whisker pads of enucleated rats throughout postnatal development. Our results show that neonatal enucleation leads to late onset plasticity of the whisker's motor system.

Proliferation rate and differentiation potential are independent during the transition from neurogenesis to gliogenesis in the mouse embryonic spinal cord.

Neural stem cells (NSC) restrict their differentiation potential as the central nervous system develops. Experimental evidence suggests that the mechanisms governing the transition from the neurogenic to the gliogenic phase irreversibly affect the ability of NSC to generate neurons. Cell cycle regulation has been associated with cell fate in different models. In this work, we assessed the temporal correlation between the loss of the neurogenic potential and cell cycle lengthening of NSC obtained from embryonic mouse spinal cords, during the transition of the neurogenic to the gliogenic phase, using neurospheres. We also used the cell cycle inhibitor Olomoucine to increase cell cycle length by decreasing the proliferation rate. Our results show that neurospheres obtained from a neurogenic stage give rise mostly to neurons, whereas those obtained from later stages produce preferentially glial cells. During the transition from neurogenesis to gliogenesis, the proliferation rate dropped, and the cell cycle length increased 1.5 folds, as monitored by DNA BrdU incorporation. Interestingly, Olomoucine-treated neurogenic-neurospheres display a reduced proliferation rate and preserve their neurogenic potential. Our results suggest that the mechanisms that restrict the differentiation potential of NSC are independent of the proliferation control.

Behavioral and Neurochemical Shifts at the Hippocampus and Frontal Cortex Are Associated to Peripheral Inflammation in Balb/c Mice Infected with Brucella abortus 2308.

Brucellosis is a zoonosis affecting 50,000,000 people annually. Most patients progress to a chronic phase of the disease in which neuropsychiatric symptoms upsurge. The biological processes underlying the progression of these symptoms are yet unclear. Peripheral inflammation mounted against Brucella may condition neurochemical shifts and hence unchained neuropsychiatric disorders. Our work aimed at establishing whether neurological, behavioral, and neurochemical disarrays are circumstantially linked to peripheral inflammation uprise secondary to Brucella abortus 2308 infections. We then evaluated, in control and Brucella-infected mice, skeletal muscle strength, movement coordination, and balance and motivation, as well as dopamine, epinephrine, norepinephrine, and serotonin availability in the cerebellum, frontal cortex, and hippocampus. Serum levels of proinflammatory cytokines and corticosterone in vehicle-injected and -infected mice were also estimated. All estimates were gathered at the infection acute and chronic phases. Our results showed that infected mice displayed motor disabilities, muscular weakness, and reduced motivation correlated with neurochemical and peripheral immunological disturbances that tended to decrease after 21 days of infection. The present observations support that disturbed peripheral inflammation and the related neurochemical disruption might lead to mood disorders in infected mice. Future experiments must be aimed at establishing causal links and to explore whether similar concepts might explain neurological and mood disorders in humans affected by brucellosis.

Arsenic species, AS3MT amount, and AS3MT gene expression in different brain regions of mouse exposed to arsenite.

Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound. Mice received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We investigated the distribution of iAs and its metabolites as well as the mRNA and protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum, mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and pituitary of mouse brain. Our findings show that methylated As metabolites are present in all brain regions studied suggesting that AS3MT is ubiquitously expressed in the brain and it is not inducible by dose of arsenite. There is also a dose-related accumulation of As species in all brain regions, with the highest accumulation observed in the pituitary. The higher distribution of arsenicals in pituitary can help to explain the neuroendocrine effects associated with iAs exposure.

Male Ejaculatory Endophenotypes: Revealing Internal Inconsistencies of the Concept in Heterosexual Copulating Rats.

Distinct manifestations of sexual behavior are conceived as separate phenotypes. Each sexual phenotype is assumed to be associated with a characteristic brain. These notions have justified the phenotyping of heterosexual copulator males based upon their ejaculation's latencies (EL) or frequencies (i.e., cumulative ejaculation number; EN). For instance, men and male rats showing premature, normal or retarded ejaculation are assumed to be distinctive endophenotypes. This concept, nonetheless, contradicts past and recent evidence that supports that sexual behavior is highly variable within each sex, and that the brain sexual functional morphology represents an intricate sexual phenotypic mosaic. Hence, for ejaculatory male endophenotypes to be considered as a valid biological concept, it must show internal consistency at various levels of organization (including genetic architectures), after being challenged by intrinsic and/or extrinsic factors. We then judged the internal consistency of the presumed ejaculatory endophenotypes by assessing whether copulatory behavior and the expression of copulation relevant genes and brain limbic structures are specific to each of the presumed EL- or EN-ejaculatory endophenotypes. To do this, copulating male rats were first phenotyped in groups consistently displaying short, average or long ejaculation latencies or very high, high, average, low or very low EN, based in their copulatory performance. Then, the internal consistency of the presumed EL- or EN-endophenotypes was tested by introducing as covariates of phenotyping other copulatory parameters (e.g., number of intromissions) in addition to EL or EN, or by analyzing the expression levels of genes encoding for estrogen receptor alpha, progesterone receptor, androgen receptor, aromatase, DNA methyl-transferase 3a and DNA methyl-transferase 1 in the amygdala, medial preoptic area, ventromedial hypothalamus and olfactory bulb. We found that even though there were group-level differences in all the variables that were studied, these differences did not add-up to create the presumed EL- or EN-ejaculatory endophenotypes. In fact, the extensive overlapping of copulatory parameters and expression levels of copulation relevant genes in limbic structures across EL- or EN-phenotyped copulating male rats, is not consistent with the hypothesis that distinct ejaculatory endophenotypes exist and that they are associated with specific brain characteristics.

Inferring lanosterol functions in the female rabbit reproductive tract based on the immunolocalization of lanosterol 14-demethylase and farnesoid beta-receptor.

Female reproductive organs have de novo synthesis of cholesterol. Some sterol molecules, intermediaries in the cholesterol synthesis, have important paracrine/autocrine actions. Lanosterol binds to the farnesoid beta-receptor (FXRß), a molecule widely expressed in the ovaries, suggesting that it may play a role in reproduction. Up to date, we know little about lanosterol functions across female reproductive organs. We described immunolocalized lanosterol 14-demethylase (LDM or CYP51A1), responsible for catalyzing the conversion of lanosterol in cholesterol, and FXRß in the ovary, oviduct, uterus, and vagina of virgin and pregnant rabbits. In virgin rats, we found CYP51A1 and FXRß immunoreactivity was found in all ovarian follicles, epithelial cells, stroma, and Graafian follicles. Also, the epithelium and stroma, as well as the smooth muscle of the oviduct, vagina, and uterus showed CYP51A1 and FXRß immunoreactivity. In pregnant dams, we observed the presence of CYP51A1 and FXRß immunoreactivity in the corpora lutea, giant uterine cells, and trophoblastic cells. The presence of CYP51A1 and FXRß support that lanosterol participates in diverse reproductive processes, including follicular maturation, transport of gametes and zygote, implantation of blastocyst, lubrication, and contraction of the vagina, secretion of female prostate, and control of delivery mediated by pelvic muscles contraction.

Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch syndrome fibroblasts.

Recently, mutations in the RNA polymerase III subunit A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A has important roles in transcription regulation of small RNAs, including tRNA, 5S rRNA, and 7SK rRNA. We aim to describe the cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control patient were cultured in vitro. The mutation caused a decrease in the expression of wildtype POLR3A mRNA and POLR3A protein and a sharp increase in mutant protein expression. In addition, there was an increase in the nuclear localization of the mutant protein. These changes were associated with an increase in the number and area of nucleoli and to a high increase in the expression of pP53 and pH2AX. All these changes were associated with premature senescence. The present observations add to our understanding of the differences between Hutchinson-Gilford progeria syndrome and WRS and opens new alternatives to study cell senesce and human aging.

Remodelling sympathetic innervation in rat pancreatic islets ontogeny.

BACKGROUND: Pancreatic islets are not fully developed at birth and it is not clear how they are vascularised and innervated. Nerve Growth Factor (NGF) is required to guide sympathetic neurons that innervate peripheral organs and also in cardiovascular system and ovary angiogenesis. Pancreatic beta cells of a transgenic mouse that over-expressed NGF in attracts sympathetic hyper-innervation towards them. Moreover, we have previously demonstrated that adult beta cells synthesize and secrete NGF; however, we do not know how is NGF secreted during development, nor if it might be trophic for sympathetic innervation and survival in the pancreas.We analyzed sympathetic innervation and vasculature development in rat pancreatic islets at different developmental stages; foetal (F19), early postnatal (P1), weaning period (P20) and adults. We temporarily correlated these events to NGF secretion by islet cells. RESULTS: Sympathetic fibres reached pancreatic islets in the early postnatal period, apparently following blood vessels. The maximal number of sympathetic fibres (TH immunopositive) in the periphery of the islets was observed at P20, and then fibres entered the islets and reached the core where beta cells are mainly located. The number of fibres decreased from that stage to adulthood. At all stages studied, islet cells secreted NGF and also expressed the high affinity receptor TrkA. Foetal and neonatal isolated islet cells secreted more NGF than adults. TrkA receptors were expressed at all stages in pancreatic sympathetic fibres and blood vessels. These last structures were NGF-immunoreactive only at early stages (foetal and P0). CONCLUSION: The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life.

Biotin deficiency in mice is associated with decreased serum availability of insulin-like growth factor-I.

BACKGROUND: Biotin deficiency leads to decreased weight and nose-rump length in mice. AIM OF THE STUDY: The mechanisms underlying this impairment in body growth are yet unclear. Biotin restriction, however, could affect the availability of growth hormone (GH) and/or insulin like growth factor-I (IGF-I) since both hormones control body growth. We then conducted a correlative study aimed at establishing whether biotin dietary restriction is associated with decreased GH/IGF-I serum concentrations. METHODS: Levels of GH and IGF-I were measured through ELISA in serum samples of male BALB/cAnN mice fed with: 1] standard chow diet (control diet); 2] 30% egg-white biotin-deficient diet; or 3] 30% egg-white diet supplemented with 16.4 micromol biotin per kilogram (biotin sufficient diet). Relative food consumption, as adjusted per gram of body weight, was also determined. GH and IGF-I measurements were taken individually for 20 weeks beginning at the postnatal week 3, when the animals started consuming the corresponding diets. In addition, femur's weight and longitudinal growth and the organization of its growth plate were all analyzed as indicators of GH/IGF-I function. RESULTS: No differences in relative food consumption were observed among the three groups of mice along the experimental period that was evaluated. IGF-I serum levels, but not GH ones, were decreased in biotin deficient mice. These animals also showed decreased femur's longitudinal growth, speed of lengthening and weight gain, as well as shorter and disorganized growth plates. CONCLUSIONS: This study shows that biotin dietary restriction is indeed associated with decreased availability of IGF-I and diminished long bone growth and elongation. These conditions could explain the impairment of longitudinal body growth previously reported in biotin deficient mice. Although cause-effect studies are still needed, we believe our results support the notion that biotin might modulate the availability of IGF-I.

Dopamine Released from TiO2 Semicrystalline Lattice Implants Attenuates Motor Symptoms in Rats Treated with 6-Hydroxydopamine.

The motor dysfunction featured by patients aggrieved by Parkinson's disease (PD) results from the reduction of dopamine (DA) availability in the caudate nucleus (CN). Restituting CN DA levels is therefore essential to ameliorate PD motor deficits. In this regard, nanotechnology may offer solutions to restore CN DA availability. DA, however, can be rapidly oxidized into toxic compounds if made available in situ, unprotected. Then, we tested whether a semicrystalline TiO2 lattice, implanted into the CN of 6-hydroxydopamine (6-OHDA)-lesioned, hemiparkinsonian rats, was able to release DA during a time window sufficient to attenuate motor symptoms while protecting it from the ongoing oxidation. Accordingly, implanted semicrystalline TiO2 lattices released incremental amounts of DA into the CN of lesioned rats. Motor symptoms were already attenuated by the 1st month and significantly reduced 2 months after implantation. These effects were specific since TiO2 lattices alone did not modify motor symptoms in lesioned rats. DA-unloaded or -loaded TiO2 lattices did not produce obvious symptoms of systemic or neurological toxicity nor significantly increased CN lipid peroxidation in implanted, lesioned rats at the time of sacrifice. Our results thus support that loaded TiO2 lattices are capable of releasing DA while protecting it from the ongoing oxidation when implanted into the brain. Their implantation does not cause noticeable systemic or local toxicity. On the contrary, they attenuated motor symptoms in hemiparkinsonian rats.

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity.

Bilateral eye enucleation at birth (BE) leads to an expansion of the primary somatosensory cortex (S1) in rat pups. Although increased growth of the somatosensory thalamo-cortical afferents (STCAs) in part explains S1 expansion, timing mechanisms governing S1 formation are also involved. In this work, we begin the search of a developmental clock by intending to document the existence of putative clock neurons in the somatosensory thalamus (VPM) and S1 based upon changes of spontaneous spike amplitude; a biophysical property sensitive to circadian regulation; the latter known to be shifted by enucleation. In addition, we also evaluated whether STCAs growth rate and segregation timing were modified, as parameters the clock might time. We found that spontaneous spike amplitude transiently, but significantly, increased or decreased in VPM and S1 neurons of BE rat pups, respectively, as compared to their control counterparts. The growth rate and segregation timing of STCAs was, however, unaffected by BE. These results support the existence of a developmental clock that ticks differently in the VPM and S1 after BE. This observation, together with the fact that STCAs growth rate and segregation timing is unchanged, suggests that S1 expansion in BE rats may in part be controlled at the cortical level.