The Effects of Carvacrol on Transient Receptor Potential (TRP) Channels in an Animal Model of Parkinson's Disease.

In this study, we aimed to investigate the effects of carvacrol (CA), a widely used phytochemical having anti-oxidant and neuroprotective effects, on transient receptor potential (TRP) channels in an animal model of Parkinson's disease (PD). A total of 64 adult male Spraque-Dawley rats were divided into four groups: sham-operated, PD animal model (unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA), 6 µg/µl), PD + vehicle (dimethyl sulfoxide (DMSO)) treatment, and PD + CA treatment (10 mg/kg, every other day, for 14 days). Half of the brain samples of substantia nigra pars compacta (SNpc) and striatum (CPu) were collected for immunohistochemistry and the remaining half were used for molecular analyses. CA treatment significantly increased the density of dopaminergic neurons immunolabeled with tyrosine hydroxylase and transient receptor potential canonical 1 (TRPC1) channel in the SNpc of PD animals. In contrast, the density of astrocytes immunolabeled with glial fibrillary acetic acid and transient receptor potential ankyrin 1 (TRPA1) channel significantly decreased following CA treatment in the CPu of PD animals. RT-PCR and western blot analyses showed that 6-OHDA administration significantly reduced TRPA1 and TPRPC1 mRNA expression and protein levels in both SNpc and CPu. CA treatment significantly upregulated TRPA1 expression in PD group, while TRPC1 levels did not display an alteration. Based on this data it was concluded that CA treatment might protect the number of dopaminergic neurons by reducing the reactive astrogliosis and modulating the expression of TRP channels in both neurons and astrocytes in an animal model of PD.

Behavioral and hormonal effects of prenatal and maternal separation stresses in postpartum rats.

The aim of this study was to evaluate the hormone and anxiety levels of rat dams who were exposed to prenatal and maternal separation stress paradigms. Sprague-Dawley rat dams were divided into Prenatal Stress (PS), Maternal Separation (MS), Prenatal Stress and Maternal Separation (PS+MS), and Control (C) groups. All animals were subjected to the open field test on the 21st postnatal day. Same-day blood samples were obtained from the tail vein in order to examine corticotrophin-releasing hormone (CRH), estradiol, oxytocin, epinephrine, norepinephrine, prolactin, progesterone, brain-derived neurotrophic factor (BDNF), endorphin, and vasopressin levels of animals via enzyme-linked immunosorbent assay (ELISA). Oxytocin levels were the highest in the control group and the lowest in the MS group. CRH levels in the MS group were significantly higher than in the PS group (p < .05). Intriguingly, the BDNF level was the lowest in the control and highest in the MS group. While there was a strong correlation in the CRH, vasopressin, BDNF levels in the control group, various relations were observed in the stress groups. Stressed animals exhibited several behavioral anomalies including decreased fear responses such as freezing, enhanced duration, and increased number of entries into the central zone of the open field test apparatus. PS dams exhibited reductions in estradiol and norepinephrine levels relative to control or MS dams.

Protective effects of anandamide against cisplatin-induced peripheral neuropathy in rats

Background/aim: Cisplatin (CIS) is an effective antineoplastic agent used in the treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in CIS therapy. Cannabinoids may alleviate this painful side effect. This study investigated the analgesic effects of anandamide (AN) on CIS-induced peripheral neuropathy, in vitro effects of AN in CIS neurotoxicity, and the contribution of nitric oxide (NO) in this effect. Materials and methods: This is an experimental animal study. Primary dorsal root ganglion (DRG) cultures were prepared from one-day-old rats for in vitro investigations. DRG cells were incubated with CIS (100­300 M), and AN (10, 50, 100, and 500 µM) was administered with the submaximal concentration of CIS. Female Sprague Dawley rats were divided into control, CIS, CIS+AN, CIS+AN+L-NG-nitro arginine methyl ester (LNAME). CIS was administered 3 mg/kg i.p once weekly for 5 weeks. AN (1 mg/kg i.p) or in combination with 10 mg/kg i.p LNAME was administrated 30 min before CIS injection. Mechanical allodynia, thermal hyperalgesia, and tail clip tests were performed. After intracardiac perfusion, sciatic nerves (SN), and DRGs were isolated and semi-thin sections were stained with toluidine blue and investigated histologically. SPSS v. 21.0 and Sigma STAT 3.5 were used for statistical analysis. One/two way ANOVA, Kruskal­Wallis, and Wilcoxon signed ranks tests were used. A p-value of 0.05 was accepted as significant. Results: CIS caused significant mechanical allodynia. AN and AN+LNAME significantly increased hind paw withdrawal latency in mechanical allodynia test. The degenerated axons significantly increased in CIS group, while decreased in AN group. The frequency of larger neurons seemed to be higher in CIS+AN group. Conclusion: AN may be a therapeutic alternative for the treatment of CIS-induced peripheral neuropathy. However, its central adverse effects must be considered.

Stress caused by environmental effects on the birth process and some of the labor hormones at rats: ideal birth environment and hormones.

OBJECTIVE: The aim of this study was to compare the effect of environmental conditions on the birth hormones and the labor of rats. MATERIALS AND METHODS: This Study is animal experiment. A total of of 18 pregnant Sprague Dawley rats were divided into control, stress and enriched groups. Animals in the stress group were exposed to unexpected variable stress paradigm three times a day during the third trimester of their pregnancies. Whereas animals raised in the enriched environment were kept in larger cages equipped with various toys. They were subjected to open field test for 5 minutes in the last trimester. Blood samples were taken from the tail vein at the beginning of birth, and 10 parameters (including corticotropin-releasing hormone, oxytocin, endorphin, epinephrine, norepinephrine, prolactin, estrogen, progesterone, vasopressin, and brain-derived neurotrophic factor) involved in labor were assessed. Kruskal Wallis, Mann Whitney U, and Spearman's rho correlation analysis were used to compare data. RESULTS: Interactions of hormones were significantly different among the groups. While hormonal interactions in the control group were similar to the physiological parameters, other groups displayed various results. There were significant (p < .05) differences in the values of corticotropin-releasing hormone (CRH) and vasopressin hormone levels. In the open Field test, standing distribution scores of animals displayed differences among control, stress and enriched environment groups (p < .05). CONCLUSION: These results showed that labor environment diversely affects physiology aspects of birth. It is known that many factors such as procedures in a hospital environment, birth environment, noise, and birth position affect the hormones at birth. Therefore, the birth environment, either at home or at the hospital, needs to be well-organized accordingly.

Antiamnesic effects of tofisopam against scopolamine-induced cognitive impairments in rats.

In this study, we investigated the potential therapeutic effects of tofisopam, a 2,3-benzodiazepine derivative anxiolytic, on cognitive deficits in rats with scopolamine-induced amnesia. Cognitive performance of the rats was investigated by using the Morris water maze and passive avoidance tests. Changes in motor activity were assessed by using the activity cage and Rota-rod tests and then morphological changes in the hippocampus were assessed via immunohistochemical stainings. The results indicated that scopolamine impaired learning and memory parameters in rats. Worsened cognitive performance, neuronal loss, and decreased hippocampal synaptophysin, Ki-67, and glial fibrillary acidic protein density were observed. Tofisopam administration at a dose of 50 mg/kg for seven days improved the impaired cognitive performance, enhanced the attenuated synaptic transmission in the hippocampus, increased proliferation in subgranular zones, and improved the decrease in astrocytes in amnesic rats. These findings point out the anti-amnesic effects of tofisopam with concomitant improvements in the hippocampal synaptogenesis, neurogenesis, and glial plasticity, for the first time. Presented beneficial effects of tofisopam on cognitive dysfunctions may have a notable clinical value considering the fact that one of the most important side effects of 1,4-benzodiazepines, which are classical anxiolytic drugs, is amnesia. However, these preclinical results need to be confirmed with further clinical studies, first.

Effects of maternal and postweaning high-fat diet exposure on the hippocampal functions and morphology / Efectos de la exposición de la dieta alta en grasa materna y pos lactancia en la función del hipocampo y la morfología

Unbalanced nutrition during perinatal period causes varying degrees of perturbations in the metabolism and cognitive functions of offspring. The aim of this study was to investigate effects of maternal and postweaning high-fat diet (HFD) exposure on the growth parameters, hippocampal functions and morphology of offspring in a sex-dependent manner. Spraque-Dawley rats were fed either standard (10 % fat) or saturated-fat (65 % fat) diet during their gestation and lactation period. After weaning, pups were sustained in same diet for 6 more weeks. Body mass index (BMI) of pups were monitored weekly, then spontaneous locomotor activities were recorded. Spatial learning and memory functions were analyzed by Morris Water Maze (MWM) test. Total volumetric changes of hippocampal subfields were estimated by Cavalieri method. HFD exposure produced sex-dependent alterations in BMI, serum lipid and activity levels. MWM results showed no significant difference among groups. However, retrieval indexes were higher in HFD-fed males. Total volumetric analysis of the dentate gyrus was comparable, but the pyramidal cell layer volume of HFD-fed males was lower than those of SD-fed males. Despite alterations in some growth and lipid parameters, maternal and perinatal exposure to HFD did not markedly affect cognitive functions and hippocampal morphology of offspring.

La nutrición desequilibrada durante el período perinatal causa diversos grados de perturbaciones en el metabolismo y las funciones cognitivas en neonatos. El objetivo de este estudio fue investigar los efectos de la exposición a una dieta alta en grasas (HFD) materna y posdestete en los parámetros de crecimiento, las funciones del hipocampo y la morfología de neonatos de una manera dependiente del sexo. Ratas SpragueDawley fueron alimentadas con dieta estándar (10 % grasa) o grasa saturada (65 % grasa) durante su período de gestación y lactancia. Después del destete, las crías se mantuvieron en la misma dieta durante 6 semanas. El índice de masa corporal (IMC) de las crías se controló semanalmente, luego se registraron las actividades locomotoras espontáneas. El aprendizaje espacial y las funciones de memoria se analizaron mediante la prueba Morris Water Maze (MWM). Los cambios volumétricos totales de los subcampos del hipocampo se estimaron mediante el método de Cavalieri. La exposición a HFD produjo alteraciones dependientes del sexo en el IMC, los niveles de lípidos séricos y los niveles de actividad. Los resultados de MWM no mostraron diferencias significativas entre los grupos. Sin embargo, los índices de recuperación fueron más altos en machos alimentados con HFD. El análisis volumétrico total del giro dentado fue comparable, pero el volumen de la capa de células piramidales de los machos alimentados con HFD fue menor que el de los machos alimentados con SD. A pesar de las alteraciones en algunos parámetros lipídicos y de crecimiento, la exposición materna y perinatal a HFD no afectó marcadamente las funciones cognitivas y la morfología del hipocampo de la descendencia.

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers.

Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1⁻3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.

Agmatine co-treatment attenuates allodynia and structural abnormalities in cisplatin-induced neuropathy in rats.

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 µm). Then, agmatine (10, 100, 500 µm) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration-dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin-induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L-NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L-NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, thermal hyperalgesia [corrected], and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L-NAME combination attenuated CIS-induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L-NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co-administration ameliorates cisplatin-induced neuropathy and may be a therapeutic alternative.

Modulation of Corpus Striatal Neurochemistry by Astrocytes and Vasoactive Intestinal Peptide (VIP) in Parkinsonian Rats.

The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used in animal models of Parkinson's disease. In various neurodegenerative diseases, astrocytes play direct, active, and critical roles in mediating neuronal survival and functions. Vasoactive intestinal peptide (VIP) has neurotrophic actions and modulates a number of astrocytic activities. In this study, the effects of VIP on the striatal neurochemistry were investigated in parkinsonian rats. Adult Sprague-Dawley rats were divided into sham-operated, unilaterally 6-OHDA-lesioned, and lesioned + VIP-administered (25 ng/kg i.p.) groups. VIP was first injected 1 h after the intrastriatal 6-OHDA microinjection and then every 2 days throughout 15 days. Extracellular striatal concentration of glutathione (GSH), gamma-aminobutyric acid (GABA), glutamate (GLU), and lactate were measured in microdialysates by high-performance liquid chromatography (HPLC). Quantification of GABA and activity dependent neuroprotective protein (ADNP)-expressing cells were determined by glutamic acid decarboxylase (GAD)/ADNP + glial fibrillary acidic protein (GFAP) double immunohistochemistry. Our results demonstrated that a 6-OHDA lesion significantly increased the density of astrocytes in the striatum and VIP treatment slightly reduced the gliosis. Extracellular concentration of GABA, GLU, and lactate levels did not change, but GSH level significantly increased in the striatum of parkinsonian rats. VIP treatment reduced GSH level comparable to sham-operated groups, but enhanced GABA and GLU levels. Our double labeling results showed that VIP primarily acts on neurons to increase ADNP and GAD expression for protection. These results suggest that, in the 6-OHDA-induced neurodegeneration model, astrocytes were possibly activated for forefront defensiveness by modulating striatal neurochemistry.

Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex.

Early life stress leads to psychopathological processes correlated with the predisposition of individuals. Prolonged development of the prefrontal cortex (PFC), playing a critical role in the cognition, personality and social behavior, makes it susceptible to adverse conditions. In this study, we evaluated the dendritic morphology of medial PFC neurons in rats subjected to perinatal stress exposure. Unbiased stereological counting methods showed that total number estimation of c-Fos (+) nuclei, indicating the neuronal activation upon stressful challenge, significantly increased in high anxious animals compared with low anxious and control groups, in both gender. Golgi-Cox staining of neurons displayed anxiety level- and sex-dependent reduction in the dendritic complexity and spine density of pyramidal neurons, especially in the stressed males. While the total length of dendrites were not correlational; density of spines, specifically the mushroom subtypes, showed a negative correlation with the anxiety level of stressed animals. These results suggest that medial PFC is a critical site of neural plasticity within the stressor controllability paradigm. Outcomes of early life stress might be predicted by analyzing the density and morphology of spines in the apical dendrites of pyramidal neurons in correlation with the anxiety-like behavior of animals.

Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats.

Agomelatine is an antidepressant with a distinct pharmacological mechanism of action as an MT1 and MT2 receptor agonist and as a 5-HT2C receptor antagonist. We evaluated the chronic effects of agomelatine administration (40 mg/kg, 20 weeks) on the cognitive performance of rats in the Morris water maze task. We applied unbiased stereological quantification methods to estimate the total numbers of granular and pyramidal neurons located in the dorsal hippocampus. We also analyzed the dendritic spines of pyramidal neurons in the CA1 region using the Golgi-Cox impregnation method. The agomelatine-treated group found the hidden platform more quickly than did the control group and spent significantly more time in the target quadrant. Agomelatine administration caused significant volumetric and numerical enhancements in granular and pyramidal neurons in the dentate gyrus and CA1-3 subregions, respectively. Increased densities of the mushroom and stubby types of spines, with no alteration in the thin-shaped spines, were observed in the agomelatine-treated group. These results showed that long-term agomelatine administration induced a nootropic effect supported by structural changes. Enhancement of the more stable types of dendritic spines might indicate improved adaptive capacity in hippocampal neurons. Future studies will provide a better understanding of the effect of this drug on synaptic plasticity.

Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function.

Corticospinal motor neurons (CSMN) receive, integrate, and relay cerebral cortex's input toward spinal targets to initiate and modulate voluntary movement. CSMN degeneration is central for numerous motor neuron disorders and neurodegenerative diseases. Previously, 5 patients with mutations in the ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) gene were reported to have neurodegeneration and motor neuron dysfunction with upper motor neuron involvement. To investigate the role of UCHL1 on CSMN health and stability, we used both in vivo and in vitro approaches, and took advantage of the Uchl1(nm3419) (UCHL1(-/-)) mice, which lack all UCHL1 function. We report a unique role of UCHL1 in maintaining CSMN viability and cellular integrity. CSMN show early, selective, progressive, and profound cell loss in the absence of UCHL1. CSMN degeneration, evident even at pre-symptomatic stages by disintegration of the apical dendrite and spine loss, is mediated via increased ER stress. These findings bring a novel understanding to the basis of CSMN vulnerability, and suggest UCHL1(-/-) mice as a tool to study CSMN pathology.

Rearing conditions differently affect the motor performance and cerebellar morphology of prenatally stressed juvenile rats.

The cerebellum is one of the most vulnerable parts of the brain to environmental changes. In this study, the effect of diverse environmental rearing conditions on the motor performances of prenatally stressed juvenile rats and its reflection to the cerebellar morphology were investigated. Prenatally stressed Wistar rats were grouped according to different rearing conditions (Enriched=EC, Standard=SC and Isolated=IC) after weaning. Six weeks later, male and female offspring from different litters were tested behaviorally. In rotarod and string suspension tests, females gained better scores than males. Significant gender and housing effects were observed especially on the motor functions requiring fine skills with the best performance by enriched females, but the worst by enriched males. The susceptibility of cerebellar macro- and micro-neurons to environmental conditions was compared using stereological methods. In female groups, no differences were observed in the volume proportions of cerebellar layers, soma sizes and the numerical densities of granule or Purkinje cells. However, a significant interaction between housing and gender was observed in the granule to Purkinje cell ratio of males, due to the increased numerical densities of the granule cells in enriched males. These data imply that proper functioning of the cerebellum relies on its well organized and evolutionarily conserved structure and circuitry. Although early life stress leads to long term behavioral and neurobiological consequences in the offspring, diverse rearing conditions can alter the motor skills of animals and synaptic connectivity between Purkinje and granular cells in a gender dependent manner.

The effect of simvastatin treatment on behavioral parameters, cognitive performance, and hippocampal morphology in rats fed a standard or a high-fat diet.

The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles.

Vasoactive intestinal peptide enhances striatal plasticity and prevents dopaminergic cell loss in Parkinsonian rats.

Destruction of the nigrostriatal dopaminergic pathway by the administration of 6-OHDA generates an animal model of Parkinson's disease. The main characteristic of this progressive neurological disorder is the loss of the dopaminergic neurons located in the substantia nigra pars compacta (SNc). Dopaminergic inputs from the SNc innervate the medium spiny neurons of the striatum and modulate the spontaneous activity of the primary output nuclei of the basal ganglia, globus pallidus interna, and substantia nigra pars reticulata. In our previous studies, we showed that systematically administered vasoactive intestinal peptide (VIP) is effective at reversing motor deficits, decreasing neuronal cell death, and repairing the myelin sheet in parkinsonian rats. In the current study, the effects of VIP on the dendritic morphology of the striatal neurons and the number of dopaminergic neurons in the SNc were examined in 6-OHDA-lesioned rats using Golgi-Cox staining and design-based stereological methods, respectively. Adult Sprague-Dawley rats were separated into sham-operated, bilaterally 6-OHDA lesioned and lesioned + i.p. VIP-injected (25 ng/kg) groups. VIP was first injected 1 h after the intrastriatal 6-OHDA microinjection (every 2 days for 15 days). The 6-OHDA significantly decreased the total number of dopaminergic neurons, branching, and spine density of the medium spiny neurons in the striatum. VIP significantly increased the number of neurons immunostained with tyrosine hydroxylase and the density of spines without altering the branching and the total length of dendrites. In conclusion, VIP might display synaptogenetic activity by enhancing the spine density in the striatum of the parkinsonian rats.

Effects of sertraline on behavioral alterations caused by environmental enrichment and social isolation.

Environmental conditions are known to play a critical role in the pathogenesis of affective disorders. In this study, the effects of sertraline, a selective serotonin (5-HT) reuptake inhibitor, on anxiety- and depression-like behaviors were investigated in rats reared in different housing conditions. Wistar rats of both sexes were divided into three groups according to their rearing conditions (Enriched = EC, Isolated = IC and Standard = SC), after weaning at postnatal day 21. While animals in control conditions were housed as a group of 4 rats in regular size plexiglass cages, social isolation groups were housed individually in metal cages. Animals in enriched conditions were housed as a group of 12 rats in specially designed cages equipped with different stimulating objects. Six weeks later, activitymeter, elevated plus maze, rotarod, grip, forced swimming and sucrose preference tests were applied to all animals and all of the tests were repeated after i.p. injection of sertraline (10 mg/kg/day) for 7 days. Environmental enrichment reduced the stereotypic behavior, improved the motor coordination and facilitated the learning skills in animals. However, housing conditions affected depression-like parameters, but not anxiety-like parameters. Sertraline treatment reduced the depression-like effect in EC and SC, but not in IC. It decreased anxiety-like behavior in IC while increased in EC. Socially isolated animals preferentially consumed more sucrose and water than the other groups, and interestingly, these differences became more significant following sertraline treatment. These results show that the responses of animals to anti-depressive drugs could be differentially affected by the behavioral consequences of the diverse housing conditions. Thus, to improve the treatment of depression; behavioral consequences of diverse housing conditions should be taken into consideration.

Lesion-induced synaptic plasticity in the somatosensory cortex of prenatally stressed rats.

Prenatal stress exposure causes long-lasting impairments of the behavioral and neuroendocrine responses to later stressors of the offspring. Although mechanisms underlying these effects remain largely unknown, abnormalities in the neuronal plasticity might be responsible for neurobiological alterations. This study used the whisker-to-barrel pathway as a model system to investigate the effects of prenatal stress on lesion-induced plasticity of neurons. Pregnant rats were subjected to immobilization stress during the trigeminal neurogenesis period, corresponding to gestational days 12 to 17, for three hours a day. After birth, the middle row (C) whisker follicles of pups from the control and stressed groups were electrocauterized. Ten days later, tangentially sectioned cortical hemispheres were stained with cytochrome oxidase histochemistry to calculate the volumes of each barrel row (A-E) in both lesioned and intact sides of the cortex, using stereological methods. The adrenal to body weight ratios were significantly increased in stressed animals, when compared to the controls. The pattern and total volume of the barrel subfield remained unaltered, but the lesion-induced map plasticity index, calculated as the D/C ratio, decreased in stressed animals. In addition, the BDNF (Brain Derived Neurotrophic Factor), NT-3 (neurotrophin-3) and the cyclic AMP response element binding protein (CREB) phosphorylation levels in tissue homogenates of the barrel cortices were measured using the ELISA method. In prenatally stressed animals, the BDNF and NT-3 levels were reduced on the lesioned side, but significant CREB activation was observed on the intact side of the barrel cortex. Taken together, the results show that prenatal stress exposure negatively affects critical period plasticity by reducing the expansion of active barrels following peripheral whisker lesion. These changes arise independent of CREB phosphorylation and appear to be mediated by reduced levels of neurotrophins.

Pyridoxine might not have a preventive effect on the retinyl palmitate-induced viscerocranial anomalies.

Viscerocranial anomalies are induced in the presence of various teratogens. Vitamin A-induced cleft palate formation is one of the most frequently used experimental models in these studies. However, the underlying mechanisms are not yet fully understood. Several studies have shown that exogenous vitamin A disrupts the fusion of the palatal shelves by increasing the expression of epidermal growth factor receptor (EGFR). More recently, pyridoxine (vitamin B6) has been reported to have a potentially protective effect in regard to viscerocranial malformations. Therefore, in this study, we aimed to investigate whether pyridoxine has a preventive effect on retinyl palmitate-induced viscerocranial anomalies. The frequency of gross malformations induced by retinyl palmitate, the natural form of vitamin A, has been studied in a dose dependent manner. Low doses of retinyl palmitate (100 mg/kg) exposure on embryonic day (ED) 10 caused no gross anomalies in the rat fetuses. Teratogenic effects were observed only after exposure to higher dosages (1000 mg/kg) and primarily targeted the developing eyes and palates. On the other hand, co-administration of 10mg/kg pyridoxine, at ED 9 and 10, significantly increased the frequencies of anomalies, even in the moderate dosage (500 mg/kg) group. In all cleft palates, sustained expression of EGFR in the medial edge epithelium was detected by immunohistochemistry. These results show that co-administration of pyridoxine has an inductive rather than protective effect on the formation of viscerocranial malformations after exposure to hypervitaminosis-A.

A forensic case of Munchausen's syndrome.

The case of a 37-year-old cleaning worker, who applied to the court with a claim of being fired from her job due to permanent functional loss of her left arm triggered by a stroke following a work accident, is presented. The court has forwarded the case to the forensic medicine department for further evaluation and documentation of the judicial report. Examination of the medical files has revealed that the person applied to our and other hospitals with various symptoms simulating urologic, neurological, musculoskeletal, cardiovascular, and pulmonary disorders. The person had been hospitalized for extensive, costly, and often invasive medical examinations and/or treatment, and deceived the physicians into carry out unnecessary diagnostic procedures. No objective signs or evidence related to a work accident or stroke was obtained from the medical records. She has been followed up with the diagnosis of lymphangitis, thrombophlebitis and repeated cellulities since 2001, and the infection had been caused by intentional insertion of glass pieces into her left arm. The reason why she was unable to use her left arm was because of contraction related to the repeated soft tissue infection rather than the claimed work accident. This case was not only trying the medical personnel to make errors and confusion, but also attempting to mislead the judgment. Therefore, in forensic cases, medical history of patient must be evaluated carefully.

The effects of prenatal stress on the Purkinje cell neurogenesis.

In the developing cerebellum, generation times of macroneurons and microneurons occur during pre- and postnatal period, respectively. In this study, to investigate the effects of prenatal stress exposure on cerebellar neuronal development, the granule-to-Purkinje cell ratio of stressed animals was compared with their age-matched controls. In the experimental group, pregnant dams were immobilized on their gestational day 7 and 14, for 6 h. The cerebella of the offspring were removed at postnatal day (P) 30, and granule-to-Purkinje cell ratios, obtained by dividing the numerical density of granule cells (NVg) by that of Purkinje cells (NVP), were found significantly reduced (24%) in the stressed animals. Since volume fraction of granular to molecular layer or white matter to whole cortex was not affected from stress exposure, the deficit seen in this ratio reflects an existent increase in the numerical density of Purkinje cells, rather than a decrease in the number of granule cells. In parallel, the linear density of Purkinje cells (NBP) and the percentage of proliferating cells, immunolabeled with BrdU, were also found significantly higher in stressed animals. Taken together, our results demonstrate that intrauterine stress changes the morphology and numerical density of cerebellar neurons by primarily affecting the actively dividing cells during the selected stress period.