Morphine Perinatal Exposure Induces Long-Lasting Negative Emotional States in Adult Offspring Rodents.

Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This study aimed to evaluate the long-lasting neurobehavioral and nociceptive consequences in adult offspring rats and mice exposed to morphine during intrauterine/lactation periods. Pregnant rats and mice were exposed subcutaneously to morphine (10 mg/kg/day) during 42 consecutive days (from the first day of pregnancy until the last day of lactation). Offspring were weighed on post-natal days (PND) 1, 5, 10, 15, 20, 30, and 60, and behavioral tasks (experiment 1) or nociceptive responses (experiment 2) were assessed at 75 days of age (adult life). Morphine-exposed female rats displayed increased spontaneous locomotor activity. More importantly, both males and female rats perinatally exposed to morphine displayed anxiety- and depressive-like behaviors. Morphine-exposed mice presented alterations in the nociceptive responses on the writhing test. This study showed that sex difference plays a role in pain threshold and that deleterious effects of morphine during pre/perinatal periods are nonrepairable in adulthood, which highlights the long-lasting clinical consequences related to anxiety, depression, and nociceptive disorders in adulthood followed by intrauterine and lactation morphine exposure.

Aniba canelilla (Kunth) Mez (Lauraceae): A Review of Ethnobotany, Phytochemical, Antioxidant, Anti-Inflammatory, Cardiovascular, and Neurological Properties.

Aniba canelilla (Kunth) Mez, popularly known as "casca preciosa" (precious bark), falsa canela (cinnamon-scented) Casca-do-maranhão (bark of maranhão), and Folha-preciosa (precious leaf), is an aromatic species of the Lauraceae family, widely distributed in the Amazon region. In traditional medicine, it is indicated for the treatment of a great diversity of diseases, including digestive, respiratory, inflam]matory, painful, and central nervous system disorders, it is administered mainly in the form of tea or decoction orally. Its essential oil is referred to as a natural antioxidant for food preservation and disease control, showing great potential for use in the cosmetics, perfumery, and pharmaceutical products sector. The present review aimed to discuss critically and comprehensively the ethnobotanical characteristics, phytochemical constitution, and scientifically tested biological properties of A. canelilla, systematizing the knowledge about the species and proposing new perspectives for research and development. The chemical composition of A. canelilla includes 1-nitro-2-phenylethane, metyleugenol, eugenol, safrol, anabasin, anbin, tannin, α-pinene, b-pinene, b-felandren, b-caryophyllene, b-sesquifelandren, p-cymene, linalool, α-copaene, and spatulenol. Researches with ethanolic extracts, essential oils, and major constituents (1-nitro-2-phenylethane and metyleugenol) have revealed antioxidant, antinociceptive, anti-inflammatory, cardio-modulating, hypotensive (vasorelaxant), hypnotic, anxiolytic, anticholinesterase, and antibiotic properties (trypanomicidal, leishmanicidal, and antifungal). Some of these effects are potentially beneficial for aging-related diseases treatment, such as cardio and cerebrovascular, chronic inflammatory, neurological, and degenerative diseases. However, it is necessary to advance in the research of its clinical use and development of therapeutic products.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats.

Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Repeated cycles of binge-like ethanol exposure induce immediate and delayed neurobehavioral changes and hippocampal dysfunction in adolescent female rats.

Binge-like ethanol intake (BEI) is a socioeconomical problem among adolescents and increasingly affects women. BEI can leave a long-term imprint in the brain, but it is unknown if its effect on cognition and anxiety is cumulative on repeated binge-ethanol episodes. We now submitted female Wistar rats to repeated cycles of binge-like ethanol treatment by intragastrically administering ethanol (3.0 g/kg/day, 20% w/v ethanol; 3 days on/4 days off) starting at postnatal day 35 (PND35). To investigate the short-term effects of BEI during adolescence, rats underwent 1 or 4 cycles of BEI, being evaluated at PND37 and PND58, respectively: both groups displayed anxiety-like behavior in the open field and elevated plus-maze tests, as well as short-term memory deficits in the object recognition task; this was associated with transient decreases of BDNF levels and increases of GFAP levels in the hippocampus. To evaluate the short- and long-lasting effects of BEI in adulthood, rats were subjected to 8 cycles of BEI and evaluated after 7.5 h (PND86) or after 14 days of ethanol withdrawal (PND100). This caused a persistent anxiogenic profile whereas recognition memory was impaired on the short-term, but not 14 days post-administration. The reduced BDNF level observed shortly after BEI recovered upon withdrawal, whereas increased GFAP immunoreactivity was persistent up to 14 days post-administration in adulthood. These findings show that repeated binge-like ethanol episodes from adolescence to adulthood in female rats cause consistent and long-term alterations of anxiety and hippocampal astrogliosis, whereas they trigger a recognition memory deficit paralleled by lower hippocampal BDNF levels, both recovering upon ethanol withdrawal.

Neurodegeneration and Glial Response after Acute Striatal Stroke: Histological Basis for Neuroprotective Studies.

Stroke is a leading cause of death and neurological disability worldwide and striatal ischemic stroke is frequent in humans due to obstruction of middle cerebral artery. Several pathological events underlie damage progression and a comprehensive description of the pathological features following experimental stroke in both acute and chronic survival times is a necessary step for further functional studies. Here, we explored the patterns of microglial activation, astrocytosis, oligodendrocyte damage, myelin impairment, and Nogo-A immunoreactivity between 3 and 30 postlesion days (PLDs) after experimental striatal stroke in adult rats induced by microinjections of endothelin-1 (ET-1). The focal ischemia induced tissue loss concomitant with intense microglia activation between 3 and 14 PLDs (maximum at 7 PLDs), decreasing afterward. Astrocytosis was maximum around 7 PLDs. Oligodendrocyte damage and Nogo-A upregulation were higher at 3 PLDs. Myelin impairment was maximum between 7 and 14 PLDs. Nogo-A expression was higher in the first week in comparison to control. The results add important histopathological features of ET-1 induced stroke in subacute and chronic survival times. In addition, the establishment of the temporal evolution of these neuropathological events is an important step for future studies seeking suitable neuroprotective drugs targeting neuroinflammation and white matter damage.

Evaluation of the effects of chronic intoxication with inorganic mercury on memory and motor control in rats.

The aims of this study were to evaluate whether chronic intoxication with mercury chloride (HgCl2), in a low concentration over a long time, can be deposited in the central nervous tissue and to determine if this exposure induces motor and cognitive impairments. Twenty animals were intoxicated for 45 days at a dose of 0.375 mg/kg/day. After this period, the animals underwent a battery of behavioral tests, in a sequence of open field, social recognition, elevated T maze and rotarod tests. They were then sacrificed, their brains collected and the motor cortex and hippocampus dissected for quantification of mercury deposited. This study demonstrates that long-term chronic HgCl2 intoxication in rats promotes functional damage. Exposure to HgCl2 induced anxiety-related responses, short- and long-term memory impairments and motor deficits. Additionally, HgCl2 accumulated in both the hippocampus and cortex of the brain with a higher affinity for the cortex.