Intracerebroventricular Cutibacterium acnes Generates Manifestations of Alzheimer's Disease-like Pathology in the Rat Hippocampus.

The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid ß (Aß) deposits in the hippocampus; Aß aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology.

Effects of the Alpha, Beta, and Gamma Binaural Beat Brain Stimulation and Short-Term Training on Simultaneously Assessed Visuospatial and Verbal Working Memories, Signal Detection Measures, Response Times, and Intrasubject Response Time Variabilities: A Within-Subject Randomized Placebo-Controlled Clinical Trial.

Introduction: Binaural beats (BBs) are phantom sound illusions perceived when two sounds of slightly different frequencies are separately transmitted to the ears. It is suggested that some BB frequencies might entrain the brain and enhance certain cognitive functions such as working memory or attention. Nevertheless, studies in this regard are very scarce, quite controversial, and merely covering a very small portion of this vast field of research (e.g., testing only a few BB frequencies), not to mention adopting some limited methodologies (e.g., no assessment of the loudness of the BB sound, adopting only between-subject analyses, and testing only one perceptual modality). Hence, we aimed to assess the potential effects of alpha, beta, and gamma BBs on cognitive-behavioral parameters of working memory and attention examined simultaneously in two different modalities (visuospatial and auditory-verbal). Methods: This within-subject five-arm randomized placebo-controlled clinical trial included 155 trials in 31 healthy right-handed subjects (17 women, 14 men, 30.84 ± 6.16 years old). Each subject listened to 8-minute sessions of 10 Hz, 16 Hz, and 40 Hz binaural beats versus 240 Hz pure tone and silence (in random orders). In each 8-minute block, they played a dual 2-back task with feedback enabled. Their cognitive-behavioral parameters (working memory capacities, signal detection measures (hit rate, false alarm rate, sensitivity, and response bias), and reaction speed measures (response time and intrasubject response time variability)) were calculated. The effects of the sound interventions and short-term training on these working memory and attention measures were assessed statistically using mixed-model linear regressions, repeated-measures ANOVAs and ANCOVAs, Bonferroni post hoc tests, and one-sample t-tests (α = 0.05). Results: The following are some major statistically significant findings (P ≤ 0.05): In the visuospatial modality, the 10 Hz BB reduced the response time and intrasubject response time variability and reduced the extent of decline over time in the case of visuospatial working memory, sensitivity, and hit rate. In the auditory-verbal modality, the 10 Hz intervention reduced the hit rate, false alarm rate, and sensitivity. The 10 Hz intervention also caused the lowest intermodality discrepancies in hit rates and false alarm rates, the highest response time discrepancies, and negative discrepancies in working memories and sensitivities (indicating the superiority of the visuospatial modality). The response biases tended to be liberal-to-neutral in the verbal modality and rather conservative in the visuospatial modality. Reactions were faster in the visuospatial modality than the auditory-verbal one, while the intrasubject variability of reaction times was smaller in the auditory-verbal modality. Short-term training can increase the hit rate, working memory, and sensitivity and can decrease the false alarm rate and response time. Aging and reduced sound intervention volume may slow down responses and increase the intrasubject variability of response time. Faster reactions might be correlated with greater hit rates, working memories, and sensitivities and also with lower false alarm rates. Conclusions: The 8-minute alpha-band binaural beat entrainment may have a few, slight enhancing effects within the visuospatial modality, but not in both modalities combined. Short-term training can improve working memory and some cognitive parameters of attention. Some BB interventions can affect the intermodality discrepancies. There may be differences between the two modalities in terms of the response speeds and intrasubject response time variabilities. Aging can slow down the response, while increasing the volume of audio interventions may accelerate it.

Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats.

AIM OF THE STUDY: In this study, we investigated the effect of long-term administration of orexin receptor 1 (OXR1) antagonist on naloxone-precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine-dependent rats. MATERIALS AND METHODS: Wistar rats received subcutaneous (s.c.) injections of morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. In chronic groups, the OXR1 antagonist, SB-334867 (20 mg/kg, i.p.), or its vehicle, was injected repetitively from postnatal day 1 (PND1)-PND23 and then for the following seven days before each morphine injection. Meanwhile, in acute groups, SB-334867, or its vehicle, was administered before each morphine injection. In groups of rats that were designated for withdrawal experiments, naloxone (2.5 mg/kg, i.p.) was administered after the last injection of morphine. In the formalin-induced pain, the effect of OXR1 inhibition on the antinociceptive effects of morphine was measured by injecting formalin after the final morphine injection. RESULTS: Animals that received long-term SB-334867 administration before morphine injection demonstrated a significant reduction in chewing, defecation, diarrhea, grooming, teeth chattering, wet-dog shake, and writhing. Inhibiting OXR1 for a long time increased formalin-induced nociceptive behaviors in interphase and phase II of the formalin-induced pain. CONCLUSIONS: Our results indicated that the inhibition of OXR1 significantly reduces the development of morphine dependence and behavioral signs elicited by the administration of naloxone in morphine-dependent rats. Furthermore, the prolonged blockade of OXR1 might be involved in formalin-induced nociceptive behaviors.

Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus.

Maternal diabetes during pregnancy affects the development of hippocampus in the offspring. Brain-derived neurotrophic factor (BDNF) has received increasing attention for its role in regulating the survival and differentiation of neuronal cells in developing and adult brain. In the current study, we evaluated the effects of maternal diabetes and insulin treatment on expression and distribution pattern of BDNF in the hippocampus of neonatal rats at the first two postnatal weeks. We found no differences in hippocampal expression of BDNF between diabetics with normal control or insulin treated neonatal rats at postnatal day (P0) (P > 0.05 each). Nevertheless, there was a marked BDNF downregulation in both sides' hippocampi of male/female diabetic group in two-week-old offspring (P ≤ 0.05 each). Furthermore, the numerical density of BDNF+ cells was significantly reduced in the right/left dentate gyrus (DG) of male and female newborns born to diabetic animals at all studied postnatal days (P ≤ 0.05 each). In addition, a lower number of reactive cells have shown in the all hippocampal subareas in the diabetic pups at P14 (P ≤ 0.05 each). Our results have demonstrated that the insulin-treatment improves some of the negative impacts of diabetes on the expression of hippocampal BDNF in the newborns. We conclude that diabetes in pregnancy bilaterally disrupts the expression of BDNF in the hippocampus of the both male and female newborns at early postnatal days. In addition, good glycemic control by insulin in the most cases is sufficient to prevent the alterations in expression of BDNF protein in developing hippocampus.

PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury.

The significant consequences of spinal cord injury (SCI) include sensory and motor disability resulting from the death of neuronal cells and axon degeneration. In this respect, overcoming the consequences of SCI including the recovery of sensory and motor functions is considered to be a difficult tasks that requires attention to multiple aspects of treatment. The breakthrough in tissue engineering through the integration of biomaterial scaffolds and stem cells has brought a new hope for the treatment of SCI. In the present study, human endometrial stem cells (hEnSCs) were cultured with human Schwann cells (hSC) in transwells, their differentiation into nerve-like cells was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry techniques. The differentiated cells (co-hEnSC) were then seeded on the poly ε-caprolactone (PCL)/gelatin scaffolds. The SEM images displayed the favorable seeding and survival of the cells on the scaffolds. The seeded scaffolds were then transplanted into hemisected SCI rats. The growth of neuronal cells was confirmed with immunohistochemical study using NF-H as a neuronal marker. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions. The results suggested that combination therapy using the differentiated hEnSC seeded on PCL/gelatin scaffolds has the potential to heal the injured spinal cord and to limit the secondary damage.

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. RESULTS: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. CONCLUSIONS: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

The Modulatory Effect of Metabotropic Glutamate Receptor Type-1α on Spike-Wave Discharges in WAG/Rij Rats.

Modulatory function of metabotropic glutamate type 1 (mGlu1) receptors plays a crucial role in the pathophysiology of some neurological disorders, including schizophrenia and epilepsy. In this study, the expression of mGlu1α receptors in the thalamic nuclei was assessed during development of absence seizures in the WAG/Rij rats, a valid genetic animal model of absence epilepsy. In addition, the effect of pharmacological modulation of mGlu1α receptors in the laterodorsal (LD) nucleus of the thalamus on the characteristic features of bioelectrical brain activities in the WAG/Rij rats was assessed. The expression of mGlu1α receptors in the LD was assessed in four experimental groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. Agonist and antagonist of mGlu1α receptors were infused in LD in the six months old WAG/Rij (epileptic) rats. The protein level of mGlu1α receptors in the thalamus of the 6-month-old WAG/Rij rats was lower than non-epileptic animals. In addition, the distribution of mGlu1α receptors in different thalamic nuclei was lower in the 6-month-old WAG/Rij compared to age-matched Wistar rats. The gene expression of mGlu1α receptor was also significantly lower in 6-month-old WAG/Rij rats in the LD compared to other animal groups. The microinjection of mGlu1α receptors agonist and antagonist in the LD reduced the duration of spike-wave discharges (SWDs) and increased the amplitude and duration of SWDs, respectively, in 6-month-old WAG/Rij rats. The alterations of mGlu1α receptors expression in the thalamus of epileptic WAG/Rij rats as well as its modulatory effects in the generation of SWDs suggest the potential of mGlu1 receptors as a therapeutic target in absence epilepsy.

Association Between Neuregulin-1 Gene Variant (rs2439272) and Schizophrenia and Its Negative Symptoms in an Iranian Population.

Objective: Although the etiology of schizophrenia is unknown, it has a significant genetic component. A number of studies have indicated that neuregulin-1 (NRG1) gene may play a role in the pathogenesis of schizophrenia. In this study, we examined whether the rs2439272 of NRG1 is associated with schizophrenia and its negative symptoms in an Iranian population. Method: Rs2439272 was genotyped in 469 participants including 276 unrelated patients with schizophrenia and 193 healthy controls. The association of genetic risk with negative symptoms (by using panss) was examined in the total, male and female samples. COCAPHASE and CLUMP22 programs were used to compare the allele and genotype frequencies, and general linear regression was used to analyze the quantitative dependent variables by the selected variant. Results: In this study, it was revealed that the G allele of rs2439272 might be an allele with the increased risk of developing schizophrenia, especially in the male participants. In addition, significant differences were found between the G allele and GG genotype frequencies, and negative symptoms in the total and male participants. Conclusion: Our results supported the association between rs2439272 in NRG1 gene and risk of schizophrenia and its negative symptoms in an Iranian population. .

Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.

Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively. We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P = 0.032), DRD4 (P = 0.05), MB-COMT (P = 0.009), and AKT1 (P = 0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P = 0.022, P = 0.034, P = 0.035, P = 0.038, respectively), and to a lesser degree in some of the candidate genes in non-psychotic patients versus the control subjects. In general, methamphetamine dependency is associated with reduced DNA methylation and corresponding increase in expression of several key genes involved in the pathogenesis of psychotic disorders. While these epigenetic changes can be useful diagnostic biomarkers for psychosis in methamphetamine abusers, it is also consistent with the use of methyl rich diet for prevention or suppression of psychosis in these patients. However, this needs to be confirmed in future studies. © 2016 Wiley Periodicals, Inc.

Brain Derived Neurotrophic Factor Modification of Epileptiform Burst Discharges in a Temporal Lobe Epilepsy Model.

INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-ß1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-ß1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-ß1 and susceptibility to IS. METHODS: Male Wistar rats were divided into sham (receiving phosphate buffered saline within dorsal hippocampus), pilocarpine (epileptic model of TLE), single injection BDNF (epileptic rats which received single high dose of BDBF within dorsal hippocampus), and multiple injections BDNF (epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE) groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes were evaluated. RESULTS: Amplitude and frequency of epileptiform burst discharges were significantly decreased in animals treated with BDNF compared to pilocarpine group. CONCLUSION: Our findings suggested that BDNF may modulate the epileptic activity in the animal model of TLE. In addition, it may have therapeutic effect for epilepsy. More studies are necessary to clarify the exact mechanisms of BDNF effects.

Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model.

Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1ß) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex termed inflammasome. Using an SCI rat model, we found improved functional long-term recovery which is paralleled by a reduction of apoptosis after intrathecal treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of neuroinflammatory cells in the damaged area. We further examined the cellular localization and sequential expression of several inflammasomes during SCI at 6 h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was applied at the thoracic segment 9, and animals were subsequently treated with SDF-1a via intrathecal application through an osmotic pump. SCI temporally increased the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1ß) and IL-18. SDF-1a significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase-1. Immunofluorescence double-labeling demonstrated that microglia and neurons are major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence that SCI stimulates a complex scenario of inflammasome activation at the injured site and that SDF-1a-mediated neuroprotection presumably depends on the attenuation of the inflammasome complex.

Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms.

Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aß) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aß-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Aß-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aß-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aß-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway.

Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

Genistein inhibits aggregation of exogenous amyloid-beta1₋40 and alleviates astrogliosis in the hippocampus of rats.

We addressed the question of whether injection of Amyloid beta (Aß)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aß(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Aß)(1-40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aß(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Aß(1-40) inhibited the formation of Aß(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Aß(1-40)-injected hippocampus to a level similar to that observed in sham-operated rats. We conclude that the neurons in the DGlb are most sensitive to Aß(1-40), and a single dose of genistein can ameliorate Aß(1-40) induced pathology.

The role of marital status, literacy, and urbanity in suicidal behavior by burns in the province of Khorasan, Iran.

A prospective study of all suicidal behaviors by burns requiring hospitalization was conducted in the province of Khorasan, Iran, from March 21, 2005 to March 20, 2006, to examine marital status, urbanity and literacy among these patients. Data were obtained through interviews during the course of hospitalization. A total of 130 patients with suicidal behavior by burns were identified (incidence rate of 2.9 per 100,000). Females had a higher rate of suicidal behavior by burns than males (4.2 vs. 1.6 per 100,000, P < 0.001). The rate of suicidal behavior by burns was higher among single persons than married persons (4.3 vs. 3.5 per 100,000). The rate of suicidal behavior by burns among the rural population was slightly higher than the urban population (3.2 vs. 2.7 per 100,000). The high rate of suicidal behavior by burns among young, married women in Khorasan is a social tragedy.

A prospective population-based study of suicidal behavior by burns in the province of Ilam, Iran.

OBJECTIVE: The aim of this study was to examine epidemiologic characteristics of suicidal behavior by burns requiring hospitalization in the province of Ilam, Iran. METHODS: A prospective population-based study of all suicidal behaviors by burns requiring hospitalization was conducted in the province of Ilam, Iran, from March 21, 2005 to March 20, 2006. Data were obtained from patients, family members, and/or significant others through interviews during the course of hospitalization. RESULTS: A total of 51 patients with suicidal behavior by burns requiring hospitalization were identified during the study period, representing an overall incidence rate of 12.5 per 100,000 person-years (P-Y) (95% confidence interval [CI]: 9.1-16.0 per 100,000 P-Y). Women had a higher rate of suicidal behavior by burns than men (18.0 vs. 7.2 per 100,000 P-Y) (P < 0.001). The age-specific rate of suicidal behavior by burns peaked at age group 20-29 years (19.3 per 100,000 P-Y). The rate of suicidal behavior by burns was slightly higher among married persons than single persons, although not statistically significant (13.5 vs. 9.8 per 100,000 P-Y) (P = 0.25). The rate of suicidal behavior by burns among the rural population was significantly higher than the urban population (17.9 vs. 9.3 per 100,000 P-Y) (P = 0.02). The most frequent precipitating factor for suicidal behavior was marital conflicts. CONCLUSIONS: The high rate of suicidal behavior by burns among young, married women in Ilam is an alarming social tragedy. Despite substantial efforts toward improving health and human rights, persistent conditions allow violence against women in Iran and these women continue to turn to the desperate remedy of self-burning. Findings of this study highlight the need for the implementation of a well-organized approach to reduce the incidence of suicide by burns.

Genistein ameliorates learning and memory deficits in amyloid ß(1-40) rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased ß-amyloid (Aß) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aß(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aß-lesioned rats. The Aß-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aß-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aß-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress.

Suicidal behavior by burns in the province of Fars, Iran.

BACKGROUND: While suicide by burns is a relatively uncommon form of suicide in developed countries, it is one of the most common methods of suicide in the Middle East region including Iran. AIMS: To describe epidemiologic characteristics of suicidal behaviors by burns in the province of Fars, Iran. METHODS: A prospective population-based study of all suicidal behaviors by burns requiring hospitalization was conducted in the province of Fars, Iran, from March 21, 2005 to March 20, 2006. Data were obtained from patients, family members, and/or significant others through interviews during the course of hospitalization. RESULTS: A total of 125 patients with suicidal behavior by burns requiring hospitalization were identified during the study period, representing an overall incidence rate of 4.3 per 100,000 (95% Confidence Interval [CI]: 3.6-5.1). Females (6.2 per 100,000) had a higher rate of suicidal behavior by burns than males (2.4 per 100,000; p < .001). The age-specific rate of suicidal behavior by burns peaked at age 20-29 years (10.1 per 100,000). The rate of suicidal behavior by burns was higher among single (7.2 per 100,000) vs. married persons (4.2 per 100,000; p = 0.03). Single males aged 20-39 years and young married women aged 15-29 years were at greatest risk of suicidal behavior by burns. The most common precipitating factor (74.4%) for suicidal behavior was a quarrel with a family member, a relative, and/or a friend. CONCLUSIONS: The high rate of suicidal behavior by burns among young/married women in Fars is of concern. Social, cultural, and economic factors may contribute to suicidal behavior and need to be addressed through education, support, and commitment.