Early and transitory hypoactivity and olfactory alterations after chronic atrazine exposure in female Sprague-Dawley rats.

Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure.

Anorexia disrupts glutamate-glutamine homeostasis associated with astroglia in the prefrontal cortex of young female rats.

Anorexia nervosa (AN) is an eating disorder characterized by self-starvation and excessive weight loss with a notorious prevalence in young women. The neurobiology of AN is unknown but murine models, like dehydration induced anorexia (DIA), reproduce weight loss and avoidance of food despite its availability. Astrocytes are known to provide homeostatic support to neurons, but it is little explored if anorexia affects this function. In this study, we tested if DIA disrupts glutamate-glutamine homeostasis associated with astrocytes in the prefrontal cortex (PFC) of young female rats. Our results showed that anorexia reduced the redox state, as well as endogenous glutamate and glutamine. These effects correlated with a reduced expression of the glutamate transporters (GLT-1 and GLAST) and glutamine synthetase, all of them are preferentially expressed by astrocytes. Accordingly, the expression of GFAP was reduced. Anorexia reduced the astrocyte density, promoted a de-ramified morphology, and augmented the de-ramified/ramified astrocyte ratio in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), but not in the motor cortex (M2). The increase of a de-ramified phenotype correlated with increased expression of vimentin and nestin. Based on these results, we conclude that anorexia disrupts glutamate-glutamine homeostasis and the redox state associated with astrocyte dysfunction.

Infant Robot-assisted Laparoscopic Pyeloplasty: Outcomes at a Single Institution, and Tips for Safety and Success.

BACKGROUND: Since its first description, multiple reports proved efficacy and safety of the robotic platform. Further progress has been made allowing for the application of robotic surgery to smaller patients, including infants. Despite the early favorable results, the use of robot surgery in infants is still controversial and more studies are needed to confirm its benefits. OBJECTIVE: To our knowledge, we present the largest single-institution case series of robot-assisted laparoscopic pyeloplasty (RAL-P) in infants, aiming to contribute to the current literature with a guide for key technical steps and safety tips for infant RAL-P. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of a prospectively maintained database. The study protocol was approved by the institutional review board. SURGICAL PROCEDURE: Only infants (≤12 mo of age) with a diagnosis of congenital ureteropelvic junction obstruction (UPJO) undergoing primary robotic dismembered pyeloplasty were included in the study. MEASUREMENTS: We critically reviewed the clinical outcomes, described the main steps of the operation, and shared tips for a safe approach. RESULTS AND LIMITATIONS: From January 2012 to August 2019, 44 infants underwent RAL-P for UPJO--33 (75%) males and 11 (25%) females. All robotic cases were completed successfully, with no laparotomic conversions. The median age and weight were 4 (1-12) mo and 6.8 (3.8-10.5) kg, respectively. The mean operative time was 142 (±25) min. The mean estimated blood loss was 7 (±3.6) ml, and no intraoperative complications occurred. The mean length of hospital stay (LOS) was 1.4 (±0.7) d. Seven (15.6%) patients had postoperative complications-one (2%) ileus (Clavien-Dindo grade [CDG] I), four (9%) urinary tract infections (CDG II), and two (4.5%) port-site hernias (CDG III). At a median follow-up of 19 mo, the success rate was 100%. CONCLUSIONS: Given the successful outcomes, benefits of decreased LOS, and improved cosmesis, RAL-P is an appealing management option for UPJO in infants. Market release of new systems, further miniaturization of instruments, and more affordable costs will hopefully be shedding light on more complex applications. PATIENT SUMMARY: Infants (≤12 mo of age) diagnosed with ureteropelvic junction obstruction undergoing primary robotic dismembered pyeloplasty were selected and included in this study. No intraoperative complications or conversion to an open approach occurred. Seven patients (16%) developed postoperative complications-one (2%) postoperative ileus, four (9%) urinary tract infections, and two (4.5%) port-site hernias. At a median follow-up of 19 (7-66) mo, the success rate was 100%.

Raised without a father: monoparental care effects over development, sexual behavior, sexual reward, and pair bonding in prairie voles.

Around 5 % of mammals are socially monogamous and both parents provide care to the pups (biparental, BP). Prairie voles are socially monogamous rodents extensively used to understand the neurobiological basis of pair bond formation and the consequences that the absence of one parent has in the offspring. Pair bonding, characterized by selective affiliation with a sexual partner, is facilitated in prairie voles by mating for 6 h or cohabitation without mating for 24 h. It was previously shown that prairie voles raised by their mother alone (monoparental, MP) show delayed pair bond formation upon reaching adulthood. In this study we evaluated the effects of BP and MP care provided on the offspring's development, ability to detect olfactory cues, preference for sexually relevant odors, display of sexual behavior, as well as the rewarding effects of mating. We also measured dopamine and serotonin concentration in the nucleus accumbens (ventral striatum) and dorsal striatum after cohabitation and mating (CM) to determine if differences in these neurotransmitters could underlie the delay in pair bond formation in MP voles. Our data showed that MP voles received less licking/grooming than BP voles, but no developmental differences between groups were found. No differences were found in the detection and discrimination of olfactory cues or preference for sexually relevant odors, as all groups innately preferred opposite sex odors. No differences were found in the display of sexual behavior. However, CM induced reinforcing properties only in BP males, followed by a preference for their sexual partner in BP but not MP males. BP males showed an increase in dopamine turnover (DOPAC/DA and HVA/DA) in the nucleus accumbens in comparison to MP voles. No differences in dopamine, serotonin or their metabolites were found in the dorsal striatum. Our results indicate that MP voles that received less licking behavior exhibit a delay in pair bond formation possibly because the sexual interaction is not rewarding enough.

Metal brain bioaccumulation and neurobehavioral effects on the wild rodent Liomys irroratus inhabiting mine tailing areas.

Ecotoxicological studies are necessary in order to evaluate the effects of environmental exposure of chemicals on wild animals and their ecological consequences. Particularly, neurobehavioral effects of heavy metal elements on wild rodents have been scarcely investigated. In the present study, we analyzed the effect of metal bioaccumulation (Pb, As, Mg, Ni, and Zn) in the brain and in the liver on exploratory activity, learning, memory, and on some dopaminergic markers in the wild rodent Liomys irroratus living inside mine tailings, at Huautla, Morelos, Mexico. We found higher Pb concentration but lower Zn in striatum, nucleus accumbens, midbrain, and hippocampus in exposed animals in comparison to rodents from the reference site. Exposed rodents exhibited anxious behavior evaluated in the open field, while no alterations in learning were found. However, they displayed slight changes in the memory test in comparison to reference group. The neurochemical evaluation showed higher levels of dopamine and 5-hydroxyindolacetic acid in midbrain, while lower levels of metabolites dihydroxyphenyl acetic acid and homovanillic acid in striatum of exposed rodents. In addition, mRNA expression levels of dopaminergic D2 receptors in nucleus accumbens were lower in animals from the mining zone than in animals from the reference zone. This is the first study that shows that chronic environmental exposure to metals results in behavioral and neurochemical alterations in the wild rodent L. irroratus, a fact that may comprise the survival of the individuals resulting in long-term effects at the population level. Finally, we suggest the use of L. irroratus as a sentinel species for environmental biomonitoring of mining sites.

Anorexia induces a microglial associated pro-inflammatory environment and correlates with neurodegeneration in the prefrontal cortex of young female rats.

Dehydration-Induced Anorexia (DIA) is a murine model that reproduces weight loss and avoidance of food, despite its availability. The prefrontal cortex (PFC) integrates sensory inputs and updates associative learning to promote (hunger) or inhibit (satiety) food-seeking behavior. In this study we tested if anorexia induces a pro-inflammatory environment associated with microglia in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), specific subregions of the PFC involved in appetite. Our results showed that anorexia increased microglial density, promoted a de-ramified morphology and augmented the de-ramified/ramified ratio in the mPFC and OFC but not in the motor cortex. Anorexia also increased the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß. This pro-inflammatory environment associated with microglia activation correlates with neuronal damage as revealed by Fluoro Jade C (FJC) and NeuN immunolabeling. We conclude that anorexia triggers a pro-inflammatory environment associated with microglia that correlates with neurodegeneration in the mPFC and OFC.

Tryptophan supplementation helps totoaba (Totoaba macdonaldi) juveniles to regain homeostasis in high-density culture conditions.

High-density culture brings with it chronic stress situations that affect fish welfare. In order to evaluate the effect of tryptophan (Trp) levels on the response to stress, Totoaba macdonaldi juveniles were stocked at low (13.5 kg m-3) and high (27.0 kg m-3) densities (32.5 and 56.4 kg m-3, respectively, at the end of the experiment) in 100-L tanks and fed for 63 days with experimental diets containing different Trp levels: control diet CD0.42 (0.42%) and three supplemented diets with 0.99, 1.55 and 2.19% (0.99Trp, 1.55Trp and 2.19Trp, respectively) (three tanks × density × diet). The high-density stocking fed with CD0.42 diets showed significantly increased blood parameters. Trp decreased catalase (CAT) activity in low- and high-density stocking, while the superoxide dismutase (SOD) activity showed no difference. Serotonin (5-hydroxytryptamine, 5-HT) content decreased, and the serotonin turnover ratio (5-HIAA:5-HT) increased in the brains of fish fed with the CD0.42 diet. Indeed, Trp-supplemented diets helped to restore homeostasis in high-density growth conditions as evaluated by the hematological and plasma parameters as well as the serotonergic activity. When the fish were provided a diet containing moderate Trp levels, plasma cortisol increased under high-density conditions. However, no differences were observed among stock densities when totoaba were fed with the 2.19Trp diet. Notably, survival was unaffected by both Trp or densities, but weight gain (WG) decreased with the dietary Trp levels in the high density culture. In sum, Trp supplementation decreased the parameter values linked to stress response on totoaba juveniles cultured at high stock densities.

Impact and Outcomes of a Pediatric Robotic Urology Mini-Fellowship.

Introduction: In order to support practicing pediatric surgeons and urologists to safely and effectively incorporate robotic surgery into their practice, we established a 5-day mini-fellowship program with a mentor, preceptor and proctor at our institution. This study was designed to report our experience with the pediatric robotic mini-fellowship (PRM) and to evaluate the impact this course had on the participants' practice. Methods: The mini-fellowship training at our institution is provided in two modules, including upper and lower urinary tract surgery, over a 5-day period. The one to one teacher-to-attendee experience included tutorial sessions, hands-on inanimate, and animate skills training, clinical case observations and video discussions. Participants were asked to complete a detailed questionnaire on their practice patterns before and after the PRM. Results: Between 2012 and 2018, a total of 29 national and international pediatric surgeons and urologists underwent robotic renal and bladder surgery training. Twenty-six fellows (90%) completed the surveys, all of which were included for analysis. The median age at the time of fellowship was 43 years (32-63), and participants had practiced urology for a median of 76 months (3-372). All of them had a laparoscopic background, with a median experience of 120 months (12-372), and an average of 454 (± 703) laparoscopic procedures performed, including the years of training. The most common primary goals of participants were to understand the concept of robotic surgery and its applications (38.5%), and to practice in the wet lab to shorten their learning curve (38.5%). After PRM completion, 24 graduates (92%) felt likely to incorporate robotic surgery into their practice, of which 15 (58%) actually started a robotic program at their home institution. At 24 months after PRM completion, the overall number of surgeries performed with a robotic approach (RA) by these 15 participants was 478 with an average of 32 (± 44) procedures per fellow, of which 109 (23%) were extirpative (nephrectomy, partial nephrectomy, etc.), and 369 (77%) reconstructive procedures (pyeloplasty, ureteral reimplantation, etc.). Before PRM, the same 15 participants performed 844 procedures with a laparoscopic approach (LA), of which 527 (62.4%) were extirpative, and 317 (37.6%) were reconstructive surgeries. These data mark a significant switch in indications for minimally invasive surgery (MIS) in pediatric urology. The rise in the number of reconstructive procedures (37.6% LA vs. 77% RA) has shown that robotic surgery has undoubtedly facilitated the performance of more challenging procedures in a minimally invasive fashion. Conclusion: The success of a mini-fellowship program relies on the commitment of expert faculty to serve as tutorial instructors and proctors. In addition, a completely outfitted robotic laboratory with access to dry and wet lab is indispensable. A 5-day intensive PRM appears to enable postgraduate surgeons to successfully incorporate the robotic platform into their practice and to advance the complexity of minimally invasive procedures, allowing for more challenging surgeries, such as reconstructive urology.

Gestational exposure to inorganic arsenic (iAs3+) alters glutamate disposition in the mouse hippocampus and ionotropic glutamate receptor expression leading to memory impairment.

Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes. Here, we used the same gestational iAs exposure model to investigate whether the up-regulation of xCT and down-regulation of GLT-1 transporters were associated with higher levels of extracellular glutamate and changes in the expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor, responsible for excitatory fast synaptic transmission. The induction of LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also studied, as well as learning and memory formation using the water maze test. Changes in GSH levels were also tested in the hippocampus of animals exposed to iAs. Results showed increased GSH synthesis (p < 0.05), associated with significantly higher extracellular glutamate levels in iAs exposed mice. Exposure was also significantly associated with AMPA subunits down-regulation, deficient LTP induction, and lower excitability of the PP-DG pathway. In addition, animals showed deficient learning and memory in the Morris Water Maze test.

The Hypoactivity Associated with the Repeated Exposure to Atrazine Is Related to Decreases in the Specific Binding to D1-DA Receptors in the Striatum of Rats.

The herbicide atrazine (ATR) has a potential toxic effect on the neuronal circuits of the brain, specifically on two major dopaminergic pathways: the nigrostriatal and mesolimbic circuits. In this work, we repeatedly exposed adult male Sprague-Dawley rats to 6 injections of 100 mg ATR/kg of body weight (for two weeks) and one saline injection two days after ATR administration. Locomotor activity was assessed for 15 minutes and/or 2 hours after ATR or saline injection and 2 months after the final ATR administration. The specific binding of [3H]-SCH23390 to D1-DA receptors and that of [3H]-Spiperone to D2-DA receptors in the dorsal and ventral striatum were assessed 2 days and 2 months after ATR treatment. ATR administration resulted in immediate, short- and long-term hypoactivity and reduced specific binding of [3H]-SCH23390 in the dorsal striatum of rats evaluated 2 months after the last ATR injection. The specific binding of [3H]-SCH23390 in the ventral striatum and the specific binding of [3H]-Spiperone in the dorsal and ventral striatum remained unchanged at 2 days or 2 months after ATR treatment. These results, together with previous findings of our group, indicate that the nigrostriatal system is a preferential target for ATR exposure.

Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice.

Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system.

The herbicide glyphosate causes behavioral changes and alterations in dopaminergic markers in male Sprague-Dawley rat.

Glyphosate (Glyph) is the active ingredient of several herbicide formulations. Reports of Glyph exposure in humans and animal models suggest that it may be neurotoxic. To evaluate the effects of Glyph on the nervous system, male Sprague-Dawley rats were given six intraperitoneal injections of 50, 100, or 150 mg Glyph/kg BW over 2 weeks (three injections/week). We assessed dopaminergic markers and their association with locomotor activity. Repeated exposure to Glyph caused hypoactivity immediately after each injection, and it was also apparent 2 days after the last injection in rats exposed to the highest dose. Glyph did not decrease monoamines, tyrosine hydroxylase (TH), or mesencephalic TH+ cells when measured 2 or 16 days after the last Glyph injection. In contrast, Glyph decreased specific binding to D1 dopamine (DA) receptors in the nucleus accumbens (NAcc) when measured 2 days after the last Glyph injection. Microdialysis experiments showed that a systemic injection of 150 mg Glyph/kg BW decreased basal extracellular DA levels and high-potassium-induced DA release in striatum. Glyph did not affect the extracellular concentrations of 3,4-dihydroxyphenylacetic acid or homovanillic acid. These results indicate that repeated Glyph exposure results in hypoactivity accompanied by decreases in specific binding to D1-DA receptors in the NAcc, and that acute exposure to Glyph has evident effects on striatal DA levels. Additional experiments are necessary in order to unveil the specific targets of Glyph on dopaminergic system, and whether Glyph could be affecting other neurotransmitter systems involved in motor control.

Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat.

Atrazine (ATR) is used as a pre- and post-emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world. A recent study in rats has shown that chronic, daily exposure to 10 mg ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain. In order to evaluate the short-term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague-Dawley rats received six IP injections of 100 mg ATR/kg BW or vehicle over two weeks. After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D(1), or DAR-D(2). In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down-regulation of Trx-1 expression was detected shortly after the ATR treatment. Moreover, in the ventral midbrain, we found that ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression. Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge (1 mg/kg) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems. These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed.

Chronic atrazine exposure causes disruption of the spontaneous locomotor activity and alters the striatal dopaminergic system of the male Sprague-Dawley rat.

The herbicide atrazine (ATR) is widely used around the world, and is a potential toxicant of the dopaminergic systems. Nigrostriatal and mesolimbic systems are the two major dopaminergic pathways of the central nervous system; they play key roles mediating a wide array of critical motor and cognitive functions. We evaluated the effects of exposing male rats for one year to 10 mg ATR/kg B.W. on these systems using motor and cognitive tasks and measuring monoamine content in the striatum, nucleus accumbens, prefrontal cortex, and hypothalamus. ATR administration resulted in impaired motor coordination and greater spontaneous locomotor activity only after 10 to 12 months of exposure. Chronic exposure to 10 mg ATR decreased striatal dopamine, but had no effect on accumbal, hypothalamic or cortical monoamine content. Chronic ATR exposure caused discrete changes in learning tasks that involve either the striatum or the nucleus accumbens. These results indicate that chronic exposure to ATR preferentially targets the nigrostriatal dopaminergic pathway, in comparison to the other dopaminergic pathways evaluated in this study, inducing behavioral and neurochemical alterations. In order to unveil the full extent of atrazine's effects on the nervous system, other neurochemical systems should be considered in future studies.

Sustained exposure to the widely used herbicide atrazine: altered function and loss of neurons in brain monoamine systems.

The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH+) and -negative (TH-) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks.

Un método para la evaluación de riesgos para la salud en zonas mineras / Health risk assessment of minig sites

Objetivo. En este trabajo se propone un esquema de tres fases para evaluar el riesgo en salud en las zonas mineras. La validación del esquema se efectuó en una zona de San Luis Potosí, México. Material y métodos. El monitoreo incluyó análisis de metales en suelo superficial, polvo residencial y agua de pozos. La biodisponibilidad se midió como el nivel de arsénico urinario en niños de las áreas contaminadas. La evaluación toxicológica consistió en análisis de la hepatotoxicidad (niveles de aspartato transaminasa) y neurotoxicidad (niveles de dopamina y de sus metabolitos) en ratas tratadas con residuos mineros. Resultados. Se encontró contaminación por arsénico y plomo en suelo y polvo. La biodisponibilidad fue positiva: 71 por ciento de los niños analizados tuvieron niveles urinarios de arsénico por arriba del valor normal. Los estudios de toxicidad mostraron daño hepático y alteraciones neuroquímicas en las ratas tratadas con el residuo. Conclusiones. El método fue útil para demostrar el riesgo en salud y para que las autoridades decidieran instrumentar un programa de restauración en la zona