Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine.

Our goals were to determine whether chronic exposure to nicotine alters nitric oxide synthase (NOS)-dependent reactivity of cerebral (pial) arterioles and to identify a potential role for NADPH oxidase in impaired NOS-dependent responses during chronic exposure to nicotine. We measured in vivo diameter of pial arterioles to NOS-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in saline-treated rats and rats chronically treated with nicotine (2 mg.kg(-1).day(-1) for 2 wk via an osmotic minipump). We found that NOS-dependent, but not -independent, vasodilatation was impaired in nicotine-treated compared with saline-treated rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased in rats treated with nicotine compared with saline-treated rats. Furthermore, using Western blot analysis, we found that chronic exposure to nicotine increased p47phox protein in the parietal cortex. Finally, we found that apocynin (40 mg.kg(-1).day(-1)) in the drinking water to inhibit NADPH oxidase alleviated impaired NOS-dependent cerebral vasodilatation in nicotine treated rats but did not alter NOS-dependent responses in saline treated rats and did not alter NOS-independent reactivity in saline- or nicotine-treated rats. These findings suggest that chronic exposure to nicotine impairs NOS-dependent dilatation of pial arterioles by a mechanism that appears to be related to the formation of superoxide anion via activation of NADPH oxidase.     

Effects of Female Hormones (17β-Estradiol and Progesterone) on Nitric Oxide Production by Alveolar Macrophages in Rats

The effect of female sex hormones on nitric oxide (NO) production was studied in alveolar macrophages (AMs). Male rats were treated with endotoxin (LPS) intratracheally or saline as control. AMs were obtained by bronchoalveolar lavage 90 min later and were cultured in the presence or in the absence of LPS and 17β-estradiol or progesterone (10⁻⁹to 10⁻⁴M). NO production was assessed by measurement of nitrites in the medium. In some experiments, NO production by AMs was measured in intratracheally LPS-treated orchidectomized rats or in female control and ovariectomized rats. Both spontaneous and stimulated NO production were higher in AMs from female than from male rats, but without statistical significance. However, ovariectomy induced significant inhibition in spontaneous production of NO by AMs. In orchidectomized rats, the NO response by AMs to LPS stimulation relative to spontaneous NO production was significantly downregulated. Female sex hormones in physiological concentrations seem to be necessary for spontaneous NO production in female rats. Pharmacological doses of estradiol inhibitedin vitroLPS-stimulated NO production in AMs of both saline- and LPS-treated rats, and basal NO production only in LPS-treated male rats. Progesterone at 10⁻⁴M inhibited basal andin vitroLPS-stimulated NO generation by AMs of both saline- and LPS-treated male rats. In LPS-treated female ratsin vitroLPS-stimulated NO production was not affected by estradiol treatment. In ovariectomized LPS-treated female rats progesterone at 10⁻⁵M significantly inhibited NO production byin vitro-stimulated AMs. Thus female sex hormones may contribute to the gender-related differences in the immune response.     

Clonidine fails to reduce pressor responsiveness of conscious spontaneously hypertensive rats to vasopressin

Pressor responses and heart rate responses to intravenous injections (3.5-50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 micrograms/kg, i.v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the alpha 2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between alpha-adrenergic agonists and AVP.     

Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat

The beneficial effect of short-term (8 days) melanocortin therapy on regenerating peripheral nerves is demonstrated using functional and electrophysiological tests. Following a crush lesion of the rat sciatic nerve, recovery of sensory function is monitored by assessing the responsiveness of the rat to a small electric current applied to the footsole. Recovery of motor function is assessed by means of an analysis of walking patterns. Normalization of the walking pattern reflects reinnervation of different muscle groups. The motor and H-reflex related sensory nerve conduction velocity of the regenerated nerves are longitudinally investigated in the same rats in which the recovery of motor and sensory function had been assessed previously. Functional tests show an enhanced recovery under melanocortin therapy, but in the end both saline- and melanocortin-treated rats show 100% recovery. However, when compared to the contralateral sciatic nerve, in the peptide-treated animals motor nerve conduction in the regenerated nerves has fully recovered after about 90 days following the crush lesion and the sensory conduction after about 120 days, whereas in the saline-treated rats a deficit of 20-40% in both motor and sensory conduction remains. This difference is observed even 214 days following crush.     

Behavioral deficits induced by lead exposure are accompanied by serotonergic and cholinergic alterations in the prefrontal cortex

The effects of long-term lead (Pb) exposure producing a blood Pb concentration of lower than 20 μg/dL, i.e. below that associated with overt neurological deficits in occupationally exposed individuals, was studied in adult rats. In order to assess gender differences, we performed parallel behavioral experiments in male and female rats. Exposure to Pb acetate (50 ppm in drinking water) for 6 months induced motor and cognitive alterations, however these effects were gender- and task-dependent. Chronic lead exposure impaired spatial learning assessed in the Morris water maze test (MWM) in both genders, whereas it only induced hyperactivity in the open field and impaired motor coordination in the rotarod test, only in male rats. Hyperactivity in male rats was accompanied by an increase in extracellular level of acetylcholine in the prefrontal cortex. Extracellular dopamine concentration in the prefrontal cortex was unaffected by lead exposure whereas serotonin concentration in the same brain area was significantly decreased in both male and female rats exposed to lead. These results unveil new molecular mechanisms underlying neuropsychiatric alterations induced by chronic lead exposure.     

Distinctive stress effects on learning during puberty

Puberty is a time of significant change in preparation for adulthood. Here, we examined how stressful experience affects cognitive and related hormonal responses in male and female rats prior to, during and after puberty. Groups were exposed to an acute stressor of brief periodic tailshocks and tested 24 h later in an associative memory task of trace eyeblink conditioning. Exposure to the stressor did not alter conditioning in males or females prior to puberty but enhanced conditioning in both males and females during puberty. The enhancement occurred in pubescent females irrespective of the estrous cycle. In adulthood, sex differences in trace conditioning and the response to stress emerged: females outperformed males under unstressed conditions, but after stressor exposure, trace conditioning in females was impaired whereas that in males was enhanced. These differences were not related to changes in gross motor activity or other nonspecific measures of performance. The effects of acute stress on corticosterone, estradiol, progesterone, and testosterone were also measured. Stressor exposure increased the concentration of corticosterone in all age groups, although sex differences were only evident in adults. All reproductive hormones except estradiol increased with age in a predictable and sex dependent fashion and none were affected by stressor exposure. Estradiol decreased in male rats across age, and remained stable for female rats. Together, these data indicate that males and female respond similarly to learning opportunities and stressful experience before and during puberty; it is in adulthood that sex differences and the opposite responses to stress arise.     

Sexual experience does not compensate for the disruptive effects of zinc sulfate--lesioning of the main olfactory epithelium on sexual behavior in male mice

Recent studies point to an important role for the main olfactory epithelium (MOE) in regulating sexual behavior in male mice. We asked whether sexual experience could compensate for the disruptive effects of lesioning the MOE on sexual behavior in male mice. Male mice, which were either sexually naive or experienced, received an intranasal irrigation of either a zinc sulfate solution to destroy the MOE or saline. Sexual behavior in mating tests with an estrous female was completely abolished in zinc sulfate-treated male mice regardless of whether subjects were sexually experienced or not before the treatment. Furthermore, zinc sulfate treatment clearly disrupted olfactory investigation of both volatile and nonvolatile odors. Destruction of the MOE by zinc sulfate treatment was confirmed by a significant reduction in the expression of Fos protein in the main olfactory bulb following exposure to estrous female urine. By contrast, vomeronasal function did not seem to be affected by zinc sulfate treatment: nasal application of estrous female urine induced similar levels of Fos protein in the mitral and granule cells of the accessory olfactory bulb (AOB) of zinc sulfate- and saline-treated males. Likewise, the expression of soybean agglutinin, which stains the axons of vomeronasal organ neurons projecting to the glomerular layer of the AOB, was similar in zinc sulfate- and saline-treated male mice. These results show that the main olfactory system is essential for the expression of sexual behavior in male mice and that sexual experience does not overcome the disruptive effects of MOE lesioning on this behavior.     

Differences between properties of male and female motor units in the rat medial gastrocnemius muscle.

Differences between motor units in hindlimb locomotor muscles of male and female Wistar rats were studied. The contractile and action potential properties of various types of motor units as well as proportions of these units in the medial gastrocnemius muscle were analyzed. Experiments were based on functional isolation and electrical stimulation of axons of single motor units. Composition of motor units was different for male and female subjects, with higher number of the fast fatigable and lower number of slow type units in male animals. The contraction and the half-relaxation times were significantly longer in male motor units, what might be due to differences in muscle size. Slower contraction of male motor units likely corresponds to lower firing rates of their motoneurons. On the other hand, no significant differences between sexes were observed with respect to force parameters of motor units (the twitch and the maximum tetanus forces), except the fast resistant units (higher force values in male muscles). The mass of the muscle was approximately 1.5 time bigger in male rats. However, the mean ratio of motor unit tetanus force to the muscle mass was almost twice smaller in this group, what indirectly suggests that muscles of male rats are composed of higher number of motor units. Finally, female muscles appeared to have higher fatigue resistance as the effect of higher proportion of resistant units (slow and fast resistant) and higher values of the fatigue index in respective motor unit types. The motor unit action potentials in female rats had slightly lower amplitudes and shorter time parameters although this difference was significant only for fast resistant units.     

The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis

A possible association between glucagon-like peptide-1 (GLP-1) analogs and incidences of pancreatitis has been suggested based on clinical studies. In male and female diabetic Zucker diabetic fatty (ZDF) rats, we investigated the effects of continuous administration of liraglutide and exenatide on biochemical [lipase, pancreatic amylase (P-amylase)] and histopathological markers of pancreatitis. Male and female ZDF rats were dosed for 13 wk with liraglutide (0.4 or 1.0 mg·kg(-1)·day(-1) sc once daily) or exenatide (0.25 mg·kg(-1)·day(-1) sc, Alzet osmotic minipumps). P-amylase and lipase plasma activity were measured, and an extended histopathological and stereological (specific cell mass and proliferation rate) evaluation of the exocrine and the endocrine pancreas was performed. Expectedly, liraglutide and exenatide lowered blood glucose and Hb A(1c) in male and female ZDF rats, whereas β-cell mass and proliferation rate were increased with greatly improved blood glucose control. Whereas neither analog affected lipase activity, small increases in P-amylase activity were observed in animals treated with liraglutide and exenatide. However, concurrent or permanent increases in lipase and P-amylase activity were never observed. Triglycerides were lowered by both GLP-1 analogs. The qualitative histopathological findings did not reveal adverse effects of liraglutide. The findings were mainly minimal in severity and focal in distribution. Similarly, the quantitative stereological analyses revealed no effects of liraglutide or exenatide on overall pancreas weight or exocrine and duct cell mass or proliferation. The present study demonstrates that, in overtly diabetic male and female ZDF rats, prolonged exposure to GLP-1 receptor agonists does not affect biochemical or histopathological markers of pancreatitis, and whereas both exenatide and liraglutide increase β-cell mass, they have no effect on the exocrine pancreas. However, clinical outcome studies and studies using primate tissues and/or studies in nonhuman primates are needed to further assess human risk.     

Renal actions of endothelin during mannitol and saline expansion.

We evaluated the effects of volume expansion with saline (0.5 ml kg-1 min-1, n = 13) and with 10% mannitol in saline (0.5 ml kg-1 min-1, n = 13) on the cardiorenal actions of endothelin-1 (ET) in rats anesthetized with sodium pentobarbital. We also evaluated to what extent the calcium channel antagonist, verapamil (0.02 mg kg-1 min-1), altered the cardiorenal actions of endothelin in volume-expanded rats (n = 10 with saline and n = 10 with mannitol). In five rats from each group, renal blood flow was measured with an electromagnetic flow probe. Sixty minutes after surgery, control clearances were collected, ET (110 ng kg-1 min-1) was then infused for 30 min, and recovery clearances were collected for 60 min. ET caused a similar increase in mean arterial blood pressure and decrease in renal blood flow and the glomerular filtration rate in the saline and mannitol groups. Verapamil significantly attenuated but did not abolish the ET-induced increase in mean arterial blood pressure in both saline- and mannitol-treated rats. By contrast, the calcium channel antagonist had no effect on the ET-induced decrease in either the glomerular filtration rate or renal blood flow in saline-treated rats, but significantly attenuated these responses to ET in mannitol-expanded animals. These data demonstrate that (i) the systemic and renal responses to ET are not affected by expansion with saline or mannitol and (ii) the renal vasoconstriction prompted by endothelin is not affected by verapamil in saline-expanded rats, but is attenuated by the Ca2+ channel antagonist during expansion with mannitol. These data suggest that during volume expansion with mannitol, but not with saline, the ET-induced renal vasoconstriction occurs primarily at intrarenal resistance sites that are dependent upon extracellular Ca2+.     

Muscle reinnervation and IGF-I synthesis are affected by exposure to heparin: an effect partially antagonized by anti-growth hormone-releasing hormone

Sciatic nerve crush was performed in 2-day-old rats, then reinnervation of the extensor digitorum longus muscle, motor neuron survival, and muscle IGF-I production were monitored. In saline-treated rats, the extent of reinnervation was around 50% and the number of EDL reinnervating motor neurons was significantly reduced. In heparin-treated rats the extent of muscle reinnervation, the recovery of nerve-evoked muscle twitch tension, and the number of motor neurons reinnervating the extensor digitorum longus muscle were greatly enhanced compared to saline-treated rats. In addition, treatment with heparin increased markedly insulin-like growth factor-I levels in denervated muscles. The concomitant exposure to anti-growth hormone releasing hormone partially abolished the stimulatory action of heparin on muscle reinnervation and prevented the increase of insulin-like growth factor-I muscle levels.     

Neonatal fluoxetine exposure alters motor performances of adolescent rats

Growing evidence from human and animal studies has shown adverse consequences of maternal usage of antidepressants in their newborn babies. To study the effects of early antidepressant exposure on motor function later in life, we treated neonatal rat pups with fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI)-type antidepressant, from the day of birth to postnatal day 4 and examined motor performance during adolescence. FLX-treated rats had reduced locomotor activities in an open field and poorer motor performance on an accelerating rotarod compared to the control group of saline-treated animals. Nevertheless, the poorer motor performance largely improved after repetitive practices. To elucidate the structural alterations in the motor system, we examined the structure of neurons in motor-related brain regions. The shape, density, and soma size of cerebellar Purkinje cells were comparable in the two groups, however, density of dendritic spine in medial spiny neurons of striatum and Layer 5 pyramidal neurons in the primary motor cortex (M1) were reduced in FLX-rats. Furthermore, the basilar dendrites in M1 Layer 5 neurons had reduced dendritic complexity than those of the control animals. The impaired dendritic structure in striatal and cortical neurons in FLX-treated rats might account for their poorer motor performances. Together, the structure and function of the motor system are affected by early FLX exposure, the long-term effects of early exposure to SSRI-type antidepressants should be concerned.     

Studies on feminine sexual behavior in the male rat: Influence of olfactory stimuli

The aim of this study was to determine if the display of lordosis behavior in the male rat could be influenced by the olfactory environment. Unexperienced adult male rats were orchidectomized (ORCH). They were primed with 75 μg estradiol benzoate and 1 mg progesterone was injected at an interval of 39 hr following long-term (LT = 3 weeks) or short-term (SHT = 8 hr 30 min) exposure to the odor of male or female urine. For 10 min they were placed in the presence of a “stimulus” male of proven sexual vigor 9 hr 30 min ± 1 hr after progesterone injection. Both LT and SHT exposure to the odor of male urine caused a significant increase in the number of ORCH rats which showed lordosis response to male mounts compared to either the ORCH rats exposed to the odor of female urine or to the controls. Following complete olfactory bulb removal (COBR), no difference was observed in the occurrence of lordosis behavior between the ORCH rats whether or not exposed to the odor of urine. For the ORCH-COBR rats exposed to male urine the proportion of animals responding to mounts did not differ from that of their nonbulbectomized counterparts. In comparing the effects of COBR vs anterior olfactory bulb removal (AOBR) lordosis behavior occurred more frequently in COBR than in AOBR-ORCH rats. The lordosis quotient (LQ) was not affected by exposure to the odor of male urine in the nonbulbectomized ORCH rats. In contrast, it appeared to be higher in both COBR and AOBR animals than in their nonbulbectomized counterparts. The olfactory bulbs were then concluded to inhibit the display of lordosis behavior in the male rat. It was also thought that the olfactory stimuli originating from male urine were capable of releasing the hypothalamic structures involved in the control of lordosis behavior of the male rat from an olfactory inhibitory influence.     

A study on specific behavioral effects of formaldehyde in the rat

It has been reported that single exposure of rats of low-level formaldehyde vapor concentrations causes significant alteration in their motor activity in the inhalation chamber. In this study, we determined the effects of formaldehyde on the locomotor activity and behavior of adult male and female Lew. 1K rats in an open field two hours after termination of a single two hours lasting inhalative exposure to approximately 0.1, 0.5, or 5 ppm. Following behavioral parameters were quantitatively examined: numbers of crossed floor squares, occurrence frequencies of air and floor sniffing, grooming, rearing, and wall climbing, as well as the incidence of fecal boli. In the open field situation, the males of all formaldehyde groups crossed significantly lower numbers of floor squares. Furthermore, significant decrease in the occurrence frequencies of floor sniffing, rearing, and wall climbing were observed. Within the female rat groups exposed to 0.5 or 5 ppm formaldehyde, a significantly decreased numbers of crossed squares were registered, while this parameter remained unchanged in the 0.1 ppm group. Other parameters were also affected by the formaldehyde inhalation (e.g. significant increase in the occurrence frequencies of air sniffing in the 0.1 and 0.5 ppm groups and significant decrease in the numbers of floor sniffing in the 0.5 and 5 ppm groups, respectively). The incidence of fecal boli was not affected in any exposure group neither in males nor in females. It is concluded from the results obtained that formaldehyde significantly affects the locomotor behavior of adult male and female rats in the open field after a single inhalative exposure to the above mentioned concentrations.     

Gender-dependent differences in serum profiles of insulin and leptin in caloric restricted rats

In the present study, we have investigated whether differences between male and female rats described in response to 40% caloric restriction (CR) were influenced by circulating level variations of sex hormones and/or insulin and leptin. Body weights (BW), organ weights, and adipose depot weights (ADW) were also measured. The most affected tissues by CR were the fat depots. Metabolically active organs were the least affected, especially more in females than in males (male weight lost: 24.3% vs. female: 17.3%). Testosterone and estradiol circulating levels did not show changes by CR. Insulin levels were decreased by CR in both genders, but was more evident in female rats than males. Leptin serum levels were higher in male rats than in females, and CR caused a circulating leptin level reduction only in males. In conclusion, our results indicate that leptin and insulin could be one of the keys of the different hormonal control of energy homeostasis in response to CR between female and male rats. In this sense, leptin serum levels correlated statistically with BW and with individual ADW only in male rats, whereas insulin serum levels correlated statistically with BW and with any of the ADW studied only in females.     

Estrogen treatment during development alters adult partner preference and reproductive behavior in female laboratory rats

There is broad acceptance for the idea that during development estradiol ‘organizes’ many aspects of reproductive behavior including partner preferences in the laboratory rat. With respect to partner preference, this idea is drawn from studies where estrogen action was in someway blocked, either through aromatase or estrogen receptor inhibition, during development in male rats. The lack of estrogens neonatally results in a decrease in the male rat's preference for females. In this study, the effect of early postnatal estradiol treatment on the partner preferences of female rats was examined as a further test of the hypothesis that male-typical partner preference is dependent upon early exposure to estrogens. Our principal finding was that increased postnatal estradiol exposure during development affected partner preference in the expected direction, and this effect was seen under several adult hormonal and behavioral testing conditions. Female rats that received exogenous estradiol during development spent more time with an estrous female and less time with a sexually active male than did cholesterol treated females. The estradiol treatment also disrupted normal female sexual behavior, receptivity, and proceptivity.     

Synergistic inhibitory effect of nicotine plus oral contraceptive on mitochondrial complex-IV is mediated by estrogen receptor-β in female rats

Chronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membrane-bound estrogen receptor-beta (ER-β) in female rats compared with exposure to nicotine alone. Mitochondrial ER-β regulates estrogen-mediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ER-β and its function could help delineate the harmful synergism between nicotine and OC. In this study, we tested the hypothesis that NOC-induced loss of mitochondrial ER-β alters the oxidative phosphorylation system protein levels and mitochondrial respiratory function. This hypothesis was tested in hippocampal mitochondria isolated from female rats exposed to saline, nicotine, OC or NOC for 16 days. NOC decreased the mitochondrial ER-β protein levels and reduced oxygen consumption and complex IV (CIV) activity by 34% and 26% compared with saline- or nicotine-administered groups, respectively. We also observed significantly low protein levels of all mitochondrial-encoded CIV subunits after NOC as compared with the nicotine or saline groups. Similarly, the silencing of ER-β reduced the phosphorylation of cyclic-AMP response element binding protein, and also reduced levels of CIV mitochondrial-encoded subunits after estrogen stimulation. Overall, these results suggest that mitochondrial ER-β loss is responsible for mitochondrial malfunction after NOC.     

Effect of the acclimation to high environmental temperature on the activity of hepatic glycogen phosphorylase (a+b and a), liver glycogen content and blood glucose level in rats

(1) Changes in the activity of hepatic glycogen phosphorylase a+b and a (GPh-ase a+b and a), liver glycogen content and blood glucose level during acclimation to moderate high environmental temperature (35±1 °C) were studied. (2) Experiments were carried out on adult fed Wistar rats of both sexes, previously given either short-term (1, 4 and 7 days) or long-term (14, 21, 30 and 60 days) exposure to high environmental temperature. The controls were continuously kept at room temperature (20±2 °C). (3) The results obtained showed that in the period of short-term exposure the liver glycogen content was decreased significantly (after the first and fourth days in male rats and after first day in female rats) and the GPh-ase a activity increased (after first day in male rats and after first, fourth and seventh day in female rats). Long-term exposure caused significant increased liver glycogen content (beginning from the 14th day in male rats and the 21st day in female rats) until the end of the acclimation period (60 days). The elevated activity of GPh-ase a persists after 14th day of exposure only in female rats while there are no significant changes over the rest of the acclimation period in both sexes. There were no significant changes in total GPh-ase activity during the whole period of exposure. Blood glucose level was significantly decreased throughout the whole period of acclimation to high environmental temperature, in both sexes (except in the 1 day exposed groups). (4) The increased activity of hepatic GPh-ase a and decreased glycogen content suggested that the short-term exposure to heat stimulates the glycogenolytical processes. Decreased blood glucose level, and elevated liver glycogen content (r=-0.7467 in male and r=-0.6548 in female rats) suggested that prolonged exposure to high environmental temperature stimulated glycogenogenesis, without changes in the GPh-ase activity.     

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28–35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.     

Follicle-stimulating hormone secretion in monosodium glutamate-lesioned rats: response to unilateral gonadectomy or porcine follicular fluid (inhibin)

The purpose of this study is to determine the acute response of pituitary FSH and LH release to unilateral gonadectomy in the MSG-treated rat, and to determine whether pFF (inhibin) can act effectively on pituitary FSH secretion in the MSG-lesioned rat. MSG (4 mg/kg B.W.) or saline was injected subcutaneously on postnatal days 2, 4, 6, 8, and 10 to male and female littermates which were used in the experiments after postnatal day 60. In the first experiment male and female littermates were bilaterally gonadectomized and bled serially for the next 72 h. At 0 h plasma FSH concentrations in MSG-treated rats were lower (p less than 0.05) than those in saline-treated controls, and for the 72 h immediately following bilateral gonadectomy FSH levels increased parallel to those of the controls, but after a significant delay. In the second experiment, MSG-treated male and female littermates were injected with 0.5 ml of pFF at several intervals following bilateral gonadectomy and decapitated 6 hours later. Injection of pFF significantly suppressed circulating FSH titers in all groups without affecting LH levels. In a third experiment, rats were unilaterally gonadectomized and blood samples were obtained at various intervals for 48 h. Following unilateral gonadectomy there was a significant transient increase in FSH levels in male or female MSG-treated rats as compared to their 0 h values; however, the absolute levels attained were barely equal to the basal concentrations observed in the saline-treated control rats. The conclusions from these data are: insufficient FSH secretion in response to unilateral gonadectomy may be responsible for the lack of compensatory gonadal hypertrophy in MSG-lesioned rats, pituitary response to inhibin is apparently unaltered by MSG toxicity, and the MSG-lesioned rat is a useful model to study the differential control mechanisms of FSH and LH secretion.