Function In Adult Rats Research Articles

Effects of Neonatal Antiepileptic Drug Exposure on Cognitive, Emotional, and Motor Function in Adult Rats

Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13 resulted in adult deficits in spatial learning in the Morris water maze and decreased social exploration for all drugs tested. Phenobarbital exposure led to deficits in cued fear conditioning, risk assessment in the elevated plus maze, and sensorimotor gating as measured by prepulse inhibition, but it did not affect motor coordination on the rotorod task. In contrast, phenytoin and lamotrigine exposure led to impaired rotorod performance, but no deficits in sensorimotor gating. Phenytoin, but not lamotrigine or phenobarbital, increased exploration in the open field. Phenytoin and phenobarbital, but not lamotrigine, disrupted cued fear conditioning. These results indicate that AED administration during a limited sensitive postnatal period is sufficient to cause a range of behavioral deficits later in life, and the specific profile of behavioral deficits varies across drugs. The differences in the long-term outcomes associated with the three AEDs examined are not predicted by either the mechanism of AED action or the proapoptotic effect of the drugs. Our findings suggest that a history of AED therapy during development must be considered as a variable when assessing later-life cognitive and psychiatric outcomes.

Perinatal citalopram exposure selectively increases locus ceruleus circuit function in male rats.

Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (CTM), have been widely prescribed for major depressive disorder, not only for adult populations, but also for children and pregnant mothers. Recent evidence suggests that chronic SSRI exposure in adults increases serotonin (5-HT) levels in the raphe system and decreases norepinephrine (NE) locus ceruleus (LC) neural activity, suggesting a robust opposing interaction between these two monoamines. In contrast, perinatal SSRI exposure induces a long-lasting downregulation of the 5-HT-raphe system, which is opposite to that seen with chronic adult treatment. Therefore, the goal of the present investigation was to test the hypothesis that perinatal CTM exposure (20 mg/kg/d) from postnatal day 1 (PN1) to PN10 leads to hyperexcited NE-LC circuit function in adult rats (>PN90). Our single-neuron LC electrophysiological data demonstrated an increase in spontaneous and stimulus-driven neural activity, including an increase in phasic bursts in CTM-exposed animals. In addition, we demonstrated a corresponding immunoreactive increase in the rate-limiting catalyzing catecholamine enzyme (tyrosine hydroxylase) within the LC and their neocortical target sites compared to saline controls. Moreover, these effects were only evident in male exposed rats, suggesting a sexual dimorphism in neural development after SSRI exposure. Together, these results indicate that administration of SSRIs during a sensitive period of brain development results in long-lasting alterations in NE-LC circuit function in adults and may be useful in understanding the etiology of pervasive developmental disorders such as autism spectrum disorder.

The immunomodulatory effects of Ipomoea carnea in rats vary depending on life stage

Ipomoea carnea Jacq. ssp. fistulosa (Mart. Ex Choisy; Convolvulaceae; I. carnea) possesses a toxic component: an indolizidine alkaloid swainsonine (SW) that has immunomodulatory effects due to its inhibition of glycoprotein metabolism. It is also known that SW is excreted into both the amniotic fluid and milk of female rats exposed to I. carnea. Thus, the aim of this study was to determine whether SW exposure, either in utero or from the milk of dams treated with I. carnea, modulates offspring immune function into adulthood. In addition, adult (70 days old) and juvenile rats (21 days old) were exposed to I. carnea in order to evaluate several other immune parameters: lymphoid organs relative weight and cellularity, humoral and cellular immune responses. Offspring exposed to I. carnea during lactation developed rheumatoid arthritis (RA) in adulthood after an immunogenic challenge. In addition, both adult and juvenile rats exposed to I. carnea showed discrepancies in several immune parameters, but did not exhibit any decrease in humoral immune response, which was enhanced at both ages. These findings indicate that SW modulates immune function in adult rats exposed to SW during lactation and in juvenile and adult rats exposed to SW as juveniles and adults, respectively.

Heat stress-induced hepatotoxicity and its prevention by resveratrol in rats

The high ambient temperature beyond the range of comfort zone or thermoneutral zone causes environmental heat stress (HST). It causes serious physiological dysfunction that may result in heat-related diseases and even death. The underlying mechanism in the pathogenesis of hepatic dysfunction following hyperthermic challenge and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions in adult rats are investigated in this study. Cellular damage was assessed in terms of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histology of liver. The effect of hyperthermia in altering the oxidative stress was evaluated on the basis of its influence on hepatic lipid peroxidation and antioxidant status—superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity. The current study demonstrated that HST is associated with a complex set of integrated alterations in liver, time-dependent rise in oxidative stress followed by distinct pattern of liver injury in animals. Heat-induced hepatotoxicity was assessed by increased lipid peroxidation, depletion of antioxidant enzyme activities such as SOD, CAT, GPx and tissue damages revealed by hepatic vacuolization, and widespread necrosis. The study also revealed that pretreatment with resveratrol resulted in normalizing these parameters appreciably, emphasizing the therapeutic potentials of this polyphenol. Taken together, the results suggest that an increase in free radical formation relative to loss of the antioxidant defense system during heat stress may render liver more susceptible to oxidative damage, leading to their functional inactivation. However, resveratrol supplementation can be an effective antidote in the treatment of HST-induced malfunction.

Sexual Experience Promotes Adult Neurogenesis in the Hippocampus Despite an Initial Elevation in Stress Hormones

Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute) or once daily for 14 consecutive days (chronic) and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated glucocorticoids but actually promotes neuronal growth and reduces anxiety.

Prolactin Inhibition at Mid-lactation Influences Adiposity and Thyroid Function in Adult Rats

Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition model) on milk leptin transfer, leptinemia, body composition, and thyroid function. Lactating rats were treated with bromocryptine (BRO, 1 mg/twice daily) or saline on days 7, 8, and 9 of lactation. Offspring were sacrificed 10, 21, and 90 days after birth. After treatment, BRO-treated dams showed hypoprolactinemia and hyperleptinemia, and produced less milk with lower levels of lactose and higher milk triglycerides. Milk leptin levels were lower at weaning. Offspring of BRO-treated dams had lower body weight and length as well as less visceral fat during lactation and adulthood. Total fat was also lower at weaning and adult life, whereas total protein was higher at 90 days-old. BRO offspring presented lower serum T4 and TSH at 10 days-old and weaning, respectively. When adults, these rats exhibited hypoleptinemia, lower levels of thyroid hormones, and higher TSH. Early inhibition of PRL therefore leads to offspring malnutrition and affects subsequent growth. Also, inhibition of PRL during lactation predisposes offspring to hypothyroidism; however, when the inhibition occurs during late lactation, the hypothyroidism is secondary, whereas when it is restricted to mid-lactation, the thyroid hypofunction is primary. The programming effect of milk suppression thus depends on the developmental stage of offspring.

Long-term consequences of early maternal deprivation in serotonergic activity and HPA function in adult rat

Increasing body of evidence indicates that early life stressful events may induce permanent alterations in neurodevelopment, which in turn, could lead to the development of psychopathologies in adulthood. In particular, maternal deprivation (MD) for 24 h in rats has been associated with several abnormalities in brain and behaviour during adulthood, relevant to the neurobiological substrate of anxiety disorders. The aim of the present study was to clarify the long-term effects of MD, on hypothalamo–pituitary–adrenal (HPA) axis activity and serotonergic (5-HT) function, in adulthood, subjects that have not been yet thoroughly investigated. For this purpose, Wistar rat pups were deprived from their mothers for a 24-h single period at postnatal day 9 (pnd 9) and were examined when aged 69–90 days. Plasma corticosterone and ACTH levels along with the animal's behaviour in an open field were used as indices of stress. Moreover, serotonergic activity was estimated in hypothalamus and hippocampus, key structures in the coordination of neuroendocrine and behavioural responses to stress. Interestingly, in adulthood, MD rats compared to controls, displayed decreased body weight, increased serotonergic activity and “anxiety” related behaviour, as well as elevated plasma corticosterone and ACTH levels. The findings of this study showed that MD results in long-term modifications in HPA axis and serotonergic activity indicating a clear relationship between early life stressful events and the development of anxiety-like disorders later in adulthood.

Exposure to zinc deficiency in fetal and postnatal life determines nitric oxide system activity and arterial blood pressure levels in adult rats

We had previously shown that prenatal exposure to Zn-deficient diets induces an increase in blood pressure and impairs renal function in adult rats. The aim of the present study was to investigate if moderate Zn restriction during early growth periods, fetal life and lactation would induce impairment in the vascular and renal NO system and alterations in plasma lipid profile. We also investigated if these effects persisted into adult life, even when a Zn-replete diet was provided after weaning. Pregnant rats were fed control (30 parts per million (ppm)) or low (8 ppm) Zn diets throughout gestation up to weaning. Afterwards, male offspring from low-Zn mothers were assigned to low- or control-Zn diets during 60 d. Male offspring from control mothers were fed a control diet. Animals exposed to Zn restriction showed low birth weight, increased systolic blood pressure and serum TAG levels, and decreased glomerular filtration rate in adulthood. Zn restriction induced a decrease in vascular and renal NO synthase activity and a reduced expression of the endothelial NO synthase isoform in aorta. A control-Zn diet during post-weaning growth returned TAG levels to normal but was unsuccessful in normalising systolic blood pressure, glomerular filtration rate or NO system activity in Zn-deficient offspring. Zn restriction during fetal life, lactation and/or post-weaning growth induced alterations in the vascular and renal NO system and in lipid metabolism that could contribute to the programming of hypertension and renal dysfunction in adulthood.

Morphologic and Bony Structural Changes in the Mandible After a Unilateral Injection of Botulinum Neurotoxin in Adult Rats

Previous animal experiments showed how reduced masticatory function plays an important role in the craniofacial and mandibular regions in the growing period. However, articles focusing on the effects of reduced masticatory function in adult animals are quite scarce. The purpose of this study was to evaluate the effects of reduced masticatory muscle activity on the jaw bones of adult rats. Botulinum neurotoxin type A (BTX-A) was injected into the left masseter muscle to reduce masticatory muscle function, and sequential changes in the jaw bones were investigated. Ten male 60-day-old Sprague-Dawley rats with a mean body weight of about 300 g were used. The following procedures were performed on each sample: 25 U/mL (0.3 mL) of BTX-A was injected into the left masseter muscle, whereas the right masseter muscle received an equal amount of sterilized saline solution. Ninety days after the procedure, the rats were sacrificed, and the weights of the masseter muscles were recorded. Meanwhile, direct anthropometric measurements were taken, and the cortical thickness, trabecular thickness, and bone mineral content of the skull and mandible were measured. All measurements were evaluated with statistical software. There were significant differences in all measurements on the BTX-A side compared with those on the control side. The differences included a decreased ramus height, increased gonial angle, and increased crown height of the posterior teeth on the injection side. Significant decreases in the muscle weight, bone mineral content, cortical thickness, and trabecular thickness were also seen on the paralyzed side compared with the non-injection side. We found that reduced masticatory function in adult rats affected the weight of the masseter muscle and the bony structure and dentition.

Fetal development and renal function in adult rats prenatally subjected to sodium overload

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P < 0.05). Prenatally sodium-overloaded pups showed increased U(Prot24 h) (45%, P < 0.05) but unchanged MAP, renal hemodynamics, NN and kidney Ox. Prenatally and postnatally sodium-overloaded rats showed increased U(Prot24 h) (27%, P < 0.05) and kidney Ox (44%, P < 0.05), reduced GFR (12%, P < 0.05), increased PV (26%, P < 0.05) and unchanged MAP and NN. The TG increased in both groups of treated offspring (21%, P < 0.05), whereas Chol increased only in the postnatally sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Testicular toxicity in mercuric chloride treated rats: Association with oxidative stress

Mercury has been recognized as an industrial hazard that adversely affects male reproductive systems of humans and animals. However, less information is available concerning the underlying mechanism in the pathogenesis of male reproductive dysfunction. The present study investigated the possible involvement of oxidative stress to induce oxidative deterioration of testicular functions in adult rats. Wistar male rats ( n = 132) were continuously exposed to HgCl 2 at 0, 50 and 100 ppm during 90 days through oral administration in the drinking water. Mercury exposure for 90 days resulted in an increase in the absolute and relative wet weight of the testis and a decrease in the absolute and relative wet weight of the accessory sex glands, with respect to the matched control. Marked perturbation in testosterone serum level was also detected during the treatment for the treated groups. Cauda epididymal sperm count/motility decreased significantly in the mercury-treated group and qualitative examination of testicular sections revealed a fewer mature luminal spermatozoa in comparison to the control. When the mercury-treated males were mated with normal cyclic females, mercury exposure resulted in a decline of the reproductive performance of male rats. These effects were associated with a significant increase in mercury content of testes and blood in time-dependent and dose-dependent fashion, respectively. The HgCl 2 treatment was associated with oxidative stress. Evidence of induction of oxidative stress was obtained in terms of perturbations in antioxidant defense and a significant dose-dependent increase in the testicular lipid peroxidation as a consequence of pro-oxidant exposure. Taken together, the results suggest that an increase in free radical formation relative to loss of antioxidant defense system after mercury exposure may render testis more susceptible to oxidative damage leading to their functional inactivation.

Growth Changes in Craniofacial Morphology after Reducing Masticatory Muscle Activity in Adult Rats

The purpose of this study was to evaluate the effects of reduced masticatory muscle activity on the growth of craniofacial bones in adult rats. In this study, botulinum neurotoxin type A (BTX-A) was injected into the masseter muscle to reduce adult rats' masticatory muscle function, and changes in the craniofacial bony form were investigated. Ten male Sprague-Dawley rats, with a body weight of about 300g at 60 days old, were used. The masseter muscles of the rats were injected with the following formula: 25 U/ml (0.3 ml) Botox in the left-side masseter muscle, and an equal amount of sterilized saline in the right-side masseter muscle. Ninety days after the injections, the rats were sacrificed, and the weight of masseter muscle was measured. Direct anthropometric measurements of the skull and mandible were made. All measurements were calculated using statistical software. The results showed significant changes in muscle weight and anthropometric measurements in the Botox-injected side. The changes included a decreased ramus height, and an increased gonial angle and teeth crown height. Changes in the vertical measurements were obvious. According to the present results, reduced masticatory function in adult rats affected not only the weight of the muscle, but also the craniofacial bony structure and dentition.

Cognitive dysfunction after experimental febrile seizures

While the majority of children with febrile seizures have an excellent prognosis, a small percentage are later discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures.

The Functional Role of Some Tomato Products on Lipid Profile and Liver Function in Adult Rats

This study was carried out to investigate the functional role of lycopene obtained from powder prepared from fresh tomato, tomato paste, and ketchup that contained equal amounts of lycopene based on levels of intake on body weight gain (BWG), feed intake, feed efficiency ratio (FER), lipid profiles, atherogenic index, and liver enzymes of hyperlipidemic rats. Forty-eight male albino rats were divided into two main groups: the first group (n = 6 rats) was kept on the basal diet as a normal control, while the second group (n = 42 rats) was fed a hyperlipidemic diet for 5 weeks to induce hyperlipidemia. The latter group was divided into seven subgroups: the first subgroup was the positive control group, while the others were supplemented with one of the tomato products at one of two levels (10 or 20 mg of lycopene/kg of diet). BWG, feed intake, and FER were calculated, and blood samples were collected to determine total lipids, total cholesterol, triglycerides, lipoprotein fractions, atherogenic index, and liver function in sera. Relative organ weights were also calculated. Results revealed that administration of various tomato products produced a significant reduction in feed intake except for the hyperlipidemic group that supplemented with the lower lycopene level from tomato paste. In addition, BWG and FER were not influenced by addition of tomato products at any level of intake. Hyperlipidemic rats supplemented with tomato powder, tomato paste, or ketchup showed significant improvement in almost all the parameters studied compared to the positive control group. Results showed that the higher lycopene level from tomato paste produced significant improvement in all lipid parameters, followed by 10 mg of lycopene/kg from tomato paste, which caused significant elevation in high-density lipoprotein cholesterol comparable to that of the negative control group. The lowest atherogenic index was achieved by addition of the lower lycopene level from tomato paste followed by the higher lycopene level from the same source. So, because of the positive effect of tomato products on the tested parameters an increase in consumption of tomato and its products in the diet is recommended. Nutrition education programs should be encouraged to inform the public of the importance of tomato and its products, especially tomato paste and ketchup, in decreasing the risk of hyperlipidemia.

A Comprehensive Analysis of Gait Impairment after Experimental Stroke and the Therapeutic Effect of Environmental Enrichment in Rats

Although gait changes are considered as reliable indices of stroke severity and efficacy of rehabilitative therapies in humans, data from animal models of focal ischemia are lacking. To determine the effect of stroke on gait function in adult rats with distal middle cerebral artery occlusion (MCAO), we assessed the longitudinal changes in gait using an automated computer-assisted gait analysis system. Four days after MCAO, intensity, maximal area of contact, and paw angle were significantly decreased in the affected forepaw whereas the double support time using ipsilateral paws increased. Relative print positions between the fore and hindpaws and limb coupling were also altered, suggesting that stroke affected sensorimotor status and reduced limb coordination. Except for paw angle, these impairments persisted for at least 5 weeks. However, unlike human stroke patients, stride length and stance were not affected in rats with MCAO. Environmental enrichment for 4 weeks improved paw contact area and relative print position of the affected limb and reduced double support time in ischemic rats compared with controls. Our results indicate that gait analysis provides great insight into various aspects of motor function changes in ischemic quadrupeds, and that environmental enrichment is beneficial in reducing a variety of poststroke gait impairments possibly through enhanced structural plasticity mechanisms within injured cortical neuronal networks underlying locomotor function.

Effects of autoimmunity on recovery of function in adult rats following spinal cord injury

The central nervous system (CNS) is considered to be an immune-privileged site. For a long time, autoimmunity-induced inflammation has been viewed as an important mediator of secondary damage in the CNS following injury. However, other studies also suggest that autoimmunity is protective and beneficial. To investigate whether protective autoimmunity is present following spinal cord injury (SCI), we employed neonatally thymectomized (Tx) rats which contain few T lymphocytes in their peripheral blood, and passively immunized them with T lymphocytes activated by myelin basic protein (MBP) or spinal cord homogenate (SCH). Here we report that, among Tx, sham-Tx (sTx) and normal rats that received a contusive SCI, no significant histological and behavioral differences were found, suggesting that the endogenous T lymphocytes had no significant influence on the pathogenesis of secondary SCI. In rats passively immunized with MBP- or SCH-activated T cells (MBP-T or SCH-T, respectively), similar numbers of CD4 + T cells were found to infiltrate into the injured spinal cords. However, only the MBP-T immunization showed neuroprotection, evidenced by the reduction of post-traumatic neuronal losses and improvement of functional recovery. These results collectively suggest that not all T lymphocytes against CNS antigens are neuroprotective and that a subpopulation of them, such as those of MBP-T cells, could be beneficial for SCI repair.

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes.

In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 microg/day) on postnatal days (PD) 1-21. On PD 90, dopamine transporter (DAT) immunoreactivity and [3H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to measure dopamine efflux in the same brain regions. The effects of postnatal Mn exposure on nigrostriatal functioning were evaluated by assessing rotorod performance and amphetamine-induced stereotypy in adulthood. In terms of associative processes, both cocaine-induced conditioned place preference (CPP) and sucrose-reinforced operant responding were examined. Results showed that postnatal Mn exposure caused persistent declines in DAT protein expression and [3H]dopamine uptake in the striatum and nucleus accumbens, as well as long-term reductions in striatal dopamine efflux. Rotorod performance did not differ according to exposure condition, however Mn-exposed rats did exhibit substantially more amphetamine-induced stereotypy than vehicle controls. Mn exposure did not alter performance on any aspect of the CPP task (preference, extinction, or reinstatement testing), nor did Mn affect progressive ratio responding (a measure of motivation). Interestingly, acquisition of a fixed ratio task was impaired in Mn-exposed rats, suggesting a deficit in procedural learning. In sum, these results indicate that postnatal Mn exposure causes persistent declines in various indices of presynaptic dopaminergic functioning. Mn-induced alterations in striatal functioning may have long-term impact on associative and nonassociative behavior.

Delayed Transplantation with Exogenous Neurotrophin Administration Enhances Plasticity of Corticofugal Projections after Spinal Cord Injury

Functional deficits following spinal cord injury (SCI) result from a disruption of corticofugal projections at the lesion site. Not only direct regeneration of the severed axons but also anatomical re-organization of spared corticofugal pathways can reestablish connections between the supraspinal and spinal motor centers. We have previously shown that delayed transplantation of fetal spinal cord tissue and neurotrophin administration by two weeks after SCI supported recovery of forelimb function in adult rats. The current study determined whether the same intervention enhances plasticity of corticofugal fibers at the midbrain and spinal cord level. Anterograde tracing of the left corticorubral fibers revealed that the animals with transplants and neurotrophins (BDNF or NT-3) increased the extent of the traced fibers crossing to the right red nucleus (RN), of which the axons are spared by a right cervical overhemisection lesion. More neurons in the left motor cortex were recruited by the treatment to establish connections with the right RN. The right corticorubral projections also increased the density of midline crossing fibers to the axotomized left RN in response to transplants and neurotrophins. Transplants plus NT-3, but not BDNF, significantly increased the amount of spared corticospinal fibers in the left dorsolateral funiculus at the spinal level both rostral and caudal to the lesion. These results suggest that corticofugal projections retain the capacity until at least two weeks after injury to undergo extensive reorganization along the entire neuraxis in response to transplants and neurotrophins. Targeting anatomical plasticity of corticofugal projections may be a promising strategy to enhance functional recovery following incomplete SCI.

Effects of vanadate on male rat reproductive tract histology, oxidative stress markers and androgenic enzyme activities

Vanadium has been recognized as industrial hazards that adversely affect male reproductive systems of humans and animals. However, less information is available concerning the underlying mechanism in the pathogenesis of male reproductive dysfunction. The present study investigated the possible involvement of oxidative stress to induce oxidative deterioration of testicular functions in adult rats. The results of in vitro and in vivo studies demonstrate that vanadium treatment resulted in a significant dose- and time-dependent increase in the testicular lipid peroxidation, marked inhibition in the level of superoxide dismutase and catalase activities, decreased sperm counts, and substantially inhibited the activities of Δ 53β- and 17β-hydroxysteroid dehydrogenase as well as serum testosterone level. Histopathological examination revealed inhibition of spermatogenesis and the preferential loss of maturing and elongated spermatids along with increased percent of abnormal sperm. Taken together, the results suggest that an increase in free radical formation relative to loss of antioxidant defense system during vanadium exposure may render testis more susceptible to oxidative damage leading to their functional inactivation. Thus the toxic effects of vanadium are cumulative and that vanadium produced damages in testes are dose- and time-dependent.

Effect of streptozotocin-induced diabetes on left ventricular function in adult rats: an in vivo Pinhole Gated SPECT study

BackgroundRecent studies have suggested that diabetes mellitus (DM) may cause left ventricular (LV) dysfunction directly resulting in increased susceptibility to heart failure. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The present study was aimed to assess this new imaging technique for quantifying LV function and remodeling from the Streptozotocin (STZ) rat model compared to controls.MethodsTwenty one rats were randomly assigned to control or diabetic group. Six months after the induction of diabetes by STZ, Pinhole 99 m Tc-sestamibi gated SPECT was performed for determining rat LV volumes and function. Post-mortem histopathologic analysis was performed to evaluate the determinant of LV remodeling in this model.ResultsAfter six months, the normalized to body weight LV End-systolic volume was significantly different in diabetic rats compared to controls (0.46 ± 0.02 vs 0.33 ± 0.03 μL/g; p = 0.01). The normalized LV End-diastolic volume was also different in both groups (1.51 ± 0.03 vs 0.88 ± 0.05 μL/g; p = 0.001) and the normalized stroke volume was significantly higher in STZ-rats (1.05 ± 0.02 vs 0.54 ± 0.06 μL/g; p = 0.001). The muscular fibers were thinner at histology in the diabetic rats (0.44 ± 0.07 vs 0.32 ± 0.06 AU; p = 0.01).ConclusionPinhole 99 m Tc-sestamibi gated SPECT can successfully be applied for the evaluation of cardiac function and remodeling in STZ-induced diabetic rats. In this model, LV volumes were significantly changed compared to a control population, leading to a LV dysfunction. These findings were consistent with the histopathological abnormalities. Finally, these data further suggest the presence of diabetes cardiomyopathy.