Behavioural alterations induced by intermittent ethanol intake and noise exposure in adolescent rats.

Alcohol intake and exposure to noise are common activities of human adolescents performed in entertainment contexts worldwide that can induce behavioural disturbances. Therefore, the aim of the present work was to investigate in an experimental model of adolescent animals whether noise exposure and intermittent ethanol intake, when present individually or sequentially, might be able to modify different behaviours. Adolescent Wistar rats of both sexes were subjected to voluntary intermittent ethanol intake for 1 week followed by exposure to noise for 2 h and tested in a battery of behavioural tasks. Data show that males exposed to noise experienced a deficit in associative memory (AM), increase in anxiety-like behaviours (ALB) and altered reaction to novelty (RN) when compared with sham animals, whereas females also showed an increase in risk assessment behaviours (RABs) and a decrease in exploratory activity (EA). In contrast, ethanol intake induced an increase in RAB and RN in males and females, whereas females also showed a deficit in AM and EA as well as an increase in ALB. When ethanol was ingested before noise exposure, most parameters were counteracted both in male and females, but differed among sexes. In consequence, it could be hypothesized that an environmental acute stressor like noise might trigger a behavioural counteracting induced by a previous repeated exposure to a chemical agent such as ethanol, leading to a compensation of a non-adaptive behaviour and reaching a better adjustment to the environment.

Effects of early noise exposure on hippocampal-dependent behaviors during adolescence in male rats: influence of different housing conditions.

Central nervous system (CNS) development is a very complex process that can be altered by environmental stimuli such as noise, which can generate long-term auditory and/or extra-auditory impairments. We have previously reported that early noise exposure can induce hippocampus-related behavioral alterations in postnatal day (PND) 28 adolescent rats. Furthermore, we recently found biochemical modifications in the hippocampus (HC) of these animals that seemed to endure even in more mature animals (i.e. PND35) and that have not been studied along with behavioral correlates. Thus, the aim of this work was to reveal novel data about the effects of early noise exposure on hippocampal-dependent behaviors in more mature animals. Additionally, extended enriched environment (EE) housing was evaluated to determine its capacity to induce behavioral modifications, either by its neuroprotective ability or the greater stimulation that it generates. Male Wistar rats were exposed to different noise schemes at PND7 or PND15. Upon weaning, some animals were transferred to EE whereas others were kept in standard cages. At PND35, different hippocampal-dependent behavioral assessments were performed. Results showed noise-induced behavioral changes that differed according to the scheme and age of exposure used. In addition, housing in an EE was effective either in preventing some of these changes or in inducing the appearance of new behavioral modifications. These findings suggest that CNS development would be sensitive to the effects of different type of environmental stimuli such as noise or enriched housing, leading to maladaptive behavioral changes that last even until adolescence.

Noise-induced hippocampal oxidative imbalance and aminoacidergic neurotransmitters alterations in developing male rats: Influence of enriched environment during adolescence.

Living in big cities might involuntarily expose people to high levels of noise causing auditory and/or extra-auditory impairments, including adverse effects on central nervous system (CNS) areas such as the hippocampus. In particular, CNS development is a very complex process that can be altered by environmental stimuli. We have previously shown that noise exposure of developing rats can induce hippocampal-related behavioral alterations. However, noise-induced biochemical alterations had not been studied yet. Thus, the aim of this work was to assess whether early noise exposure can affect rat hippocampal oxidative state and aminoacidergic neurotransmission tone. Additionally, the effectiveness of an enriched environment (EE) as a neuroprotective strategy was evaluated. Male Wistar rats were exposed to different noise schemes at 7 or 15 days after birth. Upon weaning, some animals were transferred to an EE whereas others were kept in standard cages. Short- and long-term measurements were performed to evaluate reactive oxygen species, thioredoxins levels and catalase activity as indicators of hippocampal oxidative status as well as glutamic acid decarboxylase and a subtype of glutamate transporter to evaluate aminoacidergic neurotransmission tone. Results showed noise-induced changes in hippocampal oxidative state and aminoacidergic neurotransmission markers that lasted until adolescence and differed according to the scheme and the age of exposure. Finally, EE housing was effective in preventing some of these changes. These findings suggest that CNS development seems to be sensitive to the effects of stressors such as noise, as well as those of an environmental stimulation, favoring prompt and lasting molecular changes.

Reducing Allostatic Load in Depression and Anxiety Disorders: Physical Activity and Yoga Practice as Add-On Therapies.

The allostatic load (AL) index constitutes a useful tool to objectively assess the biological aspects of chronic stress in clinical practice. AL index has been positively correlated with cumulative chronic stress (physical and psychosocial stressors) and with a high risk to develop pathological conditions (e.g., metabolic syndrome, cardiovascular pathology, inflammatory disorders) and the so-called stress-related psychiatric disorders, including anxiety and depressive disorders. Chronic stress has negative effects on brain neuroplasticity, especially on hippocampal neurogenesis and these effects may be reversed by antidepressant treatments. Several evidences indicate that non-pharmacological interventions based on physical activity and yoga practice may add synergizing benefits to classical treatments (antidepressant and benzodiazepines) for depression and anxiety, reducing the negative effects of chronic stress. The aim of this review is to provide a general overview of current knowledge on AL and chronic stress in relation to depression and anxiety, physical activity and yoga practice.

Exposure of Developing Male Rats to One or Multiple Noise Sessions and Different Housing Conditions: Hippocampal Thioredoxin Changes and Behavioral Alterations.

Exposure of developing rats to noise has shown to induce hippocampal-related behavioral alterations that were prevented after a week of housing in an enriched environment. However, neither the effect of repeated exposures nor its impact on key endogenous antioxidants had been studied yet. Thus, the aim of the present work was to reveal novel data about hippocampal oxidative state through the measurement of possible age-related differences in the levels of hippocampal thioredoxins in rats exposed to noise at different developmental ages and subjected to different schemes and housing conditions. In addition, the possibility that oxidative changes could underlie hippocampal-related behavioral changes was also analyzed. Developing male Wistar rats were exposed to noise for 2 h, either once or for 5 days. Upon weaning, some animals were transferred to an enriched cage for 1 week, whereas others were kept in standard cages. One week later, auditory and behavioral assessments, as well as measurement of hippocampal thioredoxin, were performed. Whereas no changes in the auditory function were observed, significant behavioral differences were found, that varied according to the age, scheme of exposure and housing condition. In addition, a significant increase in Trx-1 levels was found in all noise-exposed groups housed in standard cages. Housing animals in an enriched environment for 1 week was effective in preventing most of these changes. These findings suggest that animals become less susceptible to undergo behavioral alterations after repeated exposure to an environmental challenge, probably due to the ability of adaptation to an unfavorable condition. Moreover, it could be hypothesized that damage to younger individuals could be more easily prevented by a housing manipulation.

El LSD y su impacto en el movimiento hippie: a 105 años del nacimiento de su descubridor, el químico Dr. Albert Hofmann / LSD and Its Impact on the Hippie Movement: 105th Anniversary of the Birth of Its Finder, Dr. Albert Hofmann

Durante la mitad de la década de 1960 surgieron en San Francisco, California, USA, las primeras comunidades del movimiento hippie. La ideología hippie nació como una oposición al materialismo, al conformismo, a la burocracia, a las prohibiciones, a la discriminación racial. La droga que se puso “de moda” en aquellos años fue el LSD, sustancia descubierta accidentalmente por el químico Albert Hofmann cuando investigaba los alcaloides de un hongo que atacaba al cornezuelo del centeno. Esta droga, que es capaz de inducir estados alterados de conciencia, comparados en ocasiones con los de la esquizofrenia o la experiencia mística, forma parte de las llamadas “drogas psicodélicas”. Si bien durante los primeros años a partir de su descubrimiento el LSD se empleó casi exclusivamente con fines médicos en psiquiatría, psicoterapia e investigaciones sobre el cerebro, su consumo masivo politizó la droga, transformándola en un acto de resistencia antiestablishment. Más aún, tuvo un fuerte impacto en las distintas disciplinas del arte: la pintura, la escultura, la vestimenta y la música. En conclusión, una sustancia química inadvertidamente absorbida por su descubridor adquirió posteriormente, una masividad tal que llegó a tener influencias muy profundas sobre distintos aspectos de la vida del ciudadano común ya que, en poco tiempo, tanto la vestimenta como la música de estilo hippie, así como las distintas formas del arte, se extendieron más allá del movimiento y llegaron a todos los grupos sociales

During the mid 1960's the first communities of the hippie movement arouse in San Francisco, California, U.S.A. The hippie ideology emerged in opposition to materialism, conformism, bureaucracy, prohibitions and racial discrimination. The drug "in fashion" at that time was LSD, a substance which was accidentally discovered by the Chemist, Albert Hofmann, while conducting research on the alkaloids of the ergot fungus that grows on rye. This substance, which is capable of inducing an altered state of consciousness, as occacionally opposed to shizophrenia and mystical exprience, is part of the so called "psychedelic drugs". Although during the first years following its discovery, LSD was almost exclusively used for medical purposes in Psychiatry, Psychotherapy, and research conducted on the brain, its massive consumpltion has caused this substance to become politicized, turning into an act of resistance known as "anti-establishment". It is so much so that it has had a strong impact on the different disciplines of art: painting and sculpture, clothing and music. To sum up, LSD, a chemical substance which was inadvertently discovered by its finder became so widespread that caused very deep impact on the different aspects of life of the regular citizen since in a very short lapse, both the hippie clothing and music, as well as the different forms of art, went beyond the movement to reach every social group

El LSD y su impacto en el movimiento hippie: a 105 años del nacimiento de su descubridor, el químico Dr. Albert Hofmann / LSD and Its Impact on the Hippie Movement: 105th Anniversary of the Birth of Its Finder, Dr. Albert Hofmann

Durante la mitad de la década de 1960 surgieron en San Francisco, California, USA, las primeras comunidades del movimiento hippie. La ideología hippie nació como una oposición al materialismo, al conformismo, a la burocracia, a las prohibiciones, a la discriminación racial. La droga que se puso ôde modaö en aquellos años fue el LSD, sustancia descubierta accidentalmente por el químico Albert Hofmann cuando investigaba los alcaloides de un hongo que atacaba al cornezuelo del centeno. Esta droga, que es capaz de inducir estados alterados de conciencia, comparados en ocasiones con los de la esquizofrenia o la experiencia mística, forma parte de las llamadas ôdrogas psicodélicasö. Si bien durante los primeros años a partir de su descubrimiento el LSD se empleó casi exclusivamente con fines médicos en psiquiatría, psicoterapia e investigaciones sobre el cerebro, su consumo masivo politizó la droga, transformándola en un acto de resistencia antiestablishment. Más aún, tuvo un fuerte impacto en las distintas disciplinas del arte: la pintura, la escultura, la vestimenta y la música. En conclusión, una sustancia química inadvertidamente absorbida por su descubridor adquirió posteriormente, una masividad tal que llegó a tener influencias muy profundas sobre distintos aspectos de la vida del ciudadano común ya que, en poco tiempo, tanto la vestimenta como la música de estilo hippie, así como las distintas formas del arte, se extendieron más allá del movimiento y llegaron a todos los grupos sociales (AU)

During the mid 1960s the first communities of the hippie movement arouse in San Francisco, California, U.S.A. The hippie ideology emerged in opposition to materialism, conformism, bureaucracy, prohibitions and racial discrimination. The drug "in fashion" at that time was LSD, a substance which was accidentally discovered by the Chemist, Albert Hofmann, while conducting research on the alkaloids of the ergot fungus that grows on rye. This substance, which is capable of inducing an altered state of consciousness, as occacionally opposed to shizophrenia and mystical exprience, is part of the so called "psychedelic drugs". Although during the first years following its discovery, LSD was almost exclusively used for medical purposes in Psychiatry, Psychotherapy, and research conducted on the brain, its massive consumpltion has caused this substance to become politicized, turning into an act of resistance known as "anti-establishment". It is so much so that it has had a strong impact on the different disciplines of art: painting and sculpture, clothing and music. To sum up, LSD, a chemical substance which was inadvertently discovered by its finder became so widespread that caused very deep impact on the different aspects of life of the regular citizen since in a very short lapse, both the hippie clothing and music, as well as the different forms of art, went beyond the movement to reach every social group (AU)

Hippocampal-related memory deficits and histological damage induced by neonatal ionizing radiation exposure. Role of oxidative status.

Ionizing radiations induce oxidative stress on target tissues, mainly through the generation of reactive oxygen species (ROS). However, there are few data available on the behavioral effects of moderate doses of ionizing radiation. The aim of the present work was to evaluate the performance of adult rats irradiated at birth in different hippocampal-dependent behavioral tasks and to establish a relationship with the oxidative status and histological changes in rat hippocampus (Hip). Male Wistar rats were irradiated with 5 Gy of X rays between 24 and 48 h after birth. Thirty days later, rats were subjected to open field, object recognition and inhibitory avoidance tasks. In addition, oxidative status markers as well as protein kinase C (PKC) activity and histological changes were assessed in control and irradiated Hip. Results show an impairment in recognition and habituation memories in 30-day-old animals exposed to neonatal ionizing radiation, both at short- (ST) and at long-term (LT), whereas an improvement in associative memory was observed at ST. In addition, histological alterations were observed in irradiated Hip. Although an increase in ROS levels and PKC activity were found in irradiated Hip, no changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were observed. Taken together, our results support the hypothesis that an increased PKC activity, induced by neonatal ionizing radiation on rat Hip, could play a role in the generation of an imbalance between ROS levels and antioxidant systems and might underlie radiation-induced hippocampal histological damage as well as the Hip-dependent behavioral changes found in irradiated rats.

Long-lasting effects of neonatal ionizing radiation exposure on spatial memory and anxiety-like behavior.

Neonatal ionizing radiation exposure has been shown to induce a cerebellar cytoarchitecture disarrangement. Since cerebellar abnormalities have been linked to an impairment of behavioral functions, the aim of the present work was to investigate whether exposure of developing rats to ionizing radiations can produce behavioral deficits in the adult. Male Wistar rats were X-irradiated with 5Gy within 48h after birth and were tested in a radial maze and in an open field at 30 and 90 days post irradiation. Irradiated rats showed significative changes in spatial, exploratory, and procedural parameters in the radial maze, as well as a significative decrease in anxiety-like behavior, assessed in the open field. These results suggest that ionizing radiations can induce long-lasting spatial memory and anxiety-related changes. A relationship with radiation-induced cerebellar cytoarchitecture abnormalities supports the hypothesis that cerebellar integrity seems to be critical to achieve spatial performance and emotional behavior establishment.

Loss of hippocampal neuronal nitric oxide synthase contributes to the stress-related deficit in learning and memory.

Nitric oxide (NO) has been involved in many pathophysiological brain processes. However, the exact role of NO in the cognitive deficit associated to chronic stress exposure has not been elucidated. In this study, we investigated the participation of hippocampal NO production and their regulation by protein kinase C (PKC) in the memory impairment induced in mice subjected to chronic mild stress model (CMS). CMS mice showed a poor learning performance in both open field and passive avoidance inhibitory task respect to control mice. Histological studies showed a morphological alteration in the hippocampus of CMS mice. On the other hand, chronic stress induced a diminished NO production by neuronal nitric oxide synthase (nNOS) correlated with an increment in gamma and zeta PKC isoenzymes. Partial restoration of nNOS activity was obtained after PKC activity blockade. NO production by inducible nitric oxide synthase isoform was not detected. The magnitude of oxidative stress, evaluated by reactive oxygen species production, after excitotoxic levels of NMDA was increased in hippocampus of CMS mice. Moreover, ROS formation was higher in the presence of nNOS inhibitor in both control and CMS mice. Finally, treatment of mice with nNOS inhibitors results in behavioural alterations similar to those observed in CMS animals. These findings suggest a novel role for nNOS showing protective activity against insults that trigger tissue toxicity leading to memory impairments.

Altered nitric oxide synthase and PKC activities in cerebellum of gamma-irradiated neonatal rats.

In this study, we show that one single dose of gamma-irradiation at birth induces an inhibition of the cerebellar calcium dependent nitric oxide synthase (NOS) activity, probably correlated to the motor abnormalities and the disarrangement in the cerebellar cytoarchitecture observed in adult rats. This decrease in calcium dependent NOS activity could be associated with an increased protein kinase C (PKC) activity. PKC inhibition partially restores calcium dependent NOS activity, indicating that PKC activity could be negatively modulating the catalytic activity of calcium dependent NOS. These findings suggest that a decrease in nitric oxide (NO) production and the related increase in PKC activity could be intracellular events that participate in the onset of motor and cerebellar abnormalities induced by postnatal gamma-irradiation at early stages of life.

Ionizing radiation-induced damage on developing cerebellar granule cells cultures can be prevented by an early amifostine post-treatment.

Developing central nervous system (CNS) is highly sensitive to ionizing radiation due, in part, to reactive oxygen species (ROS) damage. A variety of compounds able to protect brain cells essentially by decreasing ROS production have been widely used to confirm ROS participation in different mechanisms of brain injury, as well as to evaluate them as therapeutic tools. To test if ionizing radiation-induced damage on immature cerebellar granule cells is mainly mediated by ROS accumulation, a free radical scavenger--amifostine (amf)--was used in an in vitro model. Moreover, the amf therapeutic effect was investigated. Results show that only an early (20-30 min) post-treatment with amf, acting through an antioxidant mechanism, has been effective in preventing cerebellar granule cell loss observed after ionizing radiation exposure in vitro. These data suggest that immature cerebellar granule cells grown in vitro are highly vulnerable to ROS damage and that a therapeutic intervention could be effective in a narrow temporal window. Moreover, radiation-induced cell death can be partially prevented by a complete limitation of ROS generation, suggesting that other mechanisms besides oxidative stress would also be responsible for the cellular damage found in this model.

Deferoxamine antioxidant activity on cerebellar granule cells gamma-irradiated in vitro.

Oxidative stress has been implicated in the pathogenesis of many neurodegenerative and neurological disorders, with reactive oxygen species (ROS) as part of the intracellular effectors of damage formed in the presence of an excess of iron. Ionizing radiation induces tissue damage on developing CNS through different simultaneous mechanisms, including ROS-induced oxidative damage; therefore, exogenously added iron chelators might contribute to protect cells from free-radical injury. Cerebellar granule cells grown in vitro were exposed to 0.3 Gy of gamma radiation, and 30-60 min before irradiation, deferoxamine (Dfx), an iron chelator, was added at different nontoxic concentrations. When cell viability and ROS levels were evaluated in Dfx-treated cultures, a partial prevention of radiation-induced cell death and ROS increase were found, being this prevention concentration independent. These data support the involvement of an iron-driven hydroxyl radical formation pathway in the acute toxic mechanism of radiation in cultures of cerebellar granule cells, being ROS-induced oxidative damage one of the mechanisms through which radiation might induce cell death. Therefore, blocking ROS production through the use of a chelating agent, such as Dfx, would be a useful therapeutic tool in different experimental models.