Luffa operculata fruit aqueous extract induces motor impairments, anxiety-like behavior, and testis damage in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Luffa operculata (L.) Cogn., Cucurbitaceae (buchinha-do-norte), aqueous extract (EBN) is popularly used to relieve symptoms of sinusitis and as abortive. AIM OF THE STUDY: As neurotoxicity and toxicity studies on the male reproductive system are scarce, the present study aimed at quantitatively addressing the question. MATERIALS AND METHODS: Male adult rats were observed in the open field (OF) and in the light-dark box test (LDB) to evaluate locomotion and anxiety. Macroscopical and microscopical alterations on the rats' testes were also studied. The rats were divided into two groups, control (GC) and experimental (GE). GE received 1.0 mg/kg per day of EBN, orally, for five consecutive days, whereas GC received water. On the 6th day, each animal was evaluated in OF and in LDB for 3 min in each apparatus. After that, the left testicles were studied. RESULTS: In the OF, GE showed decreased locomotion, increased immobility time and decreased grooming and remained for less time in the center of the apparatus. In LDB, GE showed significant difficulty in moving into the light side of the device and remained longer in the dark side, exhibiting less displacement on both sides and less transitions between sides. Testicle weights, relative weights, testicular volume, cranial-caudal and lateral-lateral axes presented an increase in relation to the GC. Microscopic changes were observed in parenchyma, lumen and diameter of seminiferous tubules. Leydig cell numbers were decreased in GE. CONCLUSIONS: The administration of EBN induced anxiety-like behavior, impaired locomotion and altered the testes morphology of rats.

Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies.

Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors.

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

AIMS: Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 µg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. MAIN METHODS: We prenatally exposed Wistar rats to LPS (100 µg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. KEY FINDINGS: Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. SIGNIFICANCE: Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation.

Single early prenatal lipopolysaccharide exposure impairs striatal monoamines and maternal care in female rats.

AIMS: Environmental information received by a mother can induce a phenotype change in her offspring, commonly known as a maternal effect (trans-generational effect). The present work verified the effects of lipopolysaccharide (LPS), which mimics bacterial infection, on maternal care and on the activity of related brain areas in F1 offspring, i.e., female rats that were prenatally exposed to LPS. MAIN METHODS: Pregnant rats received 100µg/kg of LPS intraperitoneally on gestational day (GD) 9.5. Female offspring of the F1 generation were mated to naïve males and were evaluated during their lactation period for open field, maternal and aggressive behaviors. Striatal and hypothalamic dopamine and serotonin levels and turnover were also evaluated. Furthermore, astrocyte protein expression in the nucleus accumbens (NA) was analyzed in F1 females to assess LPS-induced neuroinflammation. KEY FINDINGS: Prenatal LPS did not change open field behavior but impaired both maternal and maternal aggressive behaviors in the F1 generation. LPS exposure also reduced both striatal levels of dopamine and serotonin and its metabolites, but induced no changes in NA astrocyte expression. SIGNIFICANCE: We suggested that the observed impairments in the F1 females were a consequence of a motivational change induced by prenatal LPS, as (1) no changes in motor activity were observed, (2) prenatal LPS-exposure was reported by our group to induce motivational impairments in males, and (3) the existence of a strong connection between striatal dopaminergic activity and motivation-oriented activities. The present findings strongly indicate a maternal effect for prenatal LPS, at least for the F1 generation.