Haim Cohen

DJ-1 Protects Against Dopamine Toxicity: Implications for Parkinson’s Disease and Aging

Parkinsons disease (PD) is a common age-related neurodegenerative disorder. Dopamine neurotoxicity, mediated through oxidative stress, is implicated in disease pathogenesis. The vesicular monoamine transporter-2 (VMAT2) transfers dopamine into synaptic vesicles preparing it for exocytotic release and preventing its cytoplasmic oxidation. DJ-1 mutations cause early-onset familial PD. Here, we show that DJ-1 protects dopaminergic neurons and controls the vesicular sequestration of dopamine by upregulating VMAT2. Overexpression of DJ-1 protected cells against dopamine toxicity, reduced oxidative stress, and increased VMAT2 expression and function. Reduced DJ-1 levels resulted in opposite effects. Dopamine vesicular sequestration and its release upon depolarization were dependent on DJ-1 levels. Transcriptional regulation of VMAT2 expression by DJ-1 was confirmed by chromatin immunoprecipitation assay. The results were corroborated in vivo using 6-hydroxydopamine hemiparkinsonian mouse model and transgenic DJ-1 knockout mice. Our experimental data point to a novel potential protective function of DJ-1, which could be used as a therapeutic tool.

Facet joints arthrosis in normal and stenotic lumbar spines.

ABSTRACT: Study Design. A descriptive CT study of lumbar facet joint (FJ) arthrosis in general and spinal stenosis populations.Objective. To reveal the prevalence of FJ arthrosis in general and stenosis populations and to establish its relationship to age and gender.Summary of Background Data. FJ arthrosis is a common radiographic finding and has been suggested as a cause of low back and lower extremity pain. It is also considered a dominant player in the genesis of lumbar spinal stenosis. Although it is well accepted that FJ arthrosis is an age dependent phenomenon, controversies still exist as to its association with gender and its prevalence at different spine levels. Additionally, data on FJ arthrosis frequency in spinal stenosis population are missing.Methods. Two groups were studied. The first included 65 individuals with LSS (mean age 66 ± 10 years) and the second, 150 individuals (mean age 52 ± 19 years) without LSS related symptoms. Both left and right FJ arthrosis for each vertebral level (L3 to S1) were evaluated on CT images (Brilliance 64, Philips Medical System, Cleveland Ohio). Chi-Square, Linear-by-Linear Association and McNemar test were carried out to reveal the correlation between FJ arthrosis and demographic factors (age, gender) and prevalence at different lumbar levels in both stenosis and non-stenosis groups. Additionally, a 2-way ANOVA was used to determine the association between BMI and FJ arthrosis.Results. The rate of FJ arthrosis at L3-4 and L4-5 were significantly higher (P<0.001) in the stenotic group compared to the control. In the control group the prevalence of FJ arthrosis increases cephalo-caudally (L3-L4 = 16%, L4-L5 = 28%, L5-S1 = 55%), whereas in the stenotic group there is a sharp increase from L3-4 (27%) to L4-5 (58%), but not from L4-5 to L5-S1 (55%). No association between FJ arthrosis and gender was noted. Although, mean BMI was significantly smaller in the control group compared to the stenotic group, no association between BMI and facet arthrosis was found. In the general population the prevalence of FJ arthrosis at all three levels was greater for the right side; however, significant difference (P = 0.004) was obtained only for L3-4. In all joints studied, the prevalence of FJ arthrosis increases considerably from the young age cohort (18-39) to the old age cohort (>60). Nevertheless, 10% of the young individuals (18-39) have already manifested FJ arthrosis at L5-S1. No arthrosis at that age was observed at L3-4.Conclusion. FJ arthrosis is an age-dependent and BMI and gender-independent phenomenon. In the general population, the prevalence of FJ arthrosis increases cephalo-caudally with the highest frequency at L5-S1. In the stenotic group, the highest frequency was observed at the two caudal levels; L4-5 and L5-S1. The prevalence of FJ arthrosis was greater for the right side.Study Design. A descriptive CT study of lumbar facet joint (FJ) arthrosis in general and spinal stenosis populations. Objective. To reveal the prevalence of FJ arthrosis in general and stenosis populations and to establish its relationship to age and sex. Summary of Background Data. FJ arthrosis is a common radiographic finding and has been suggested as a cause of low back and lower extremity pain. It is also considered a dominant player in the genesis of lumbar spinal stenosis. Although it is well accepted that FJ arthrosis is an age dependent phenomenon, controversies still exist as to its association with sex and its prevalence at different spine levels. In addition, data on FJ arthrosis frequency in spinal stenosis population are missing. Methods. Two groups were studied. The first included 65 individuals with LSS (mean age = 66 ± 10 yr) and the second, 150 individuals (mean age = 52 ± 19 yr) without LSS related symptoms. Both left and right FJ arthrosis for each vertebral level (L3–S1) were evaluated on CT images (Brilliance 64, Philips Medical System, Cleveland, OH). Chi-square, Linear-by-Linear Association and McNemar test were carried out to reveal the correlation between FJ arthrosis and demographic factors (age, sex) and prevalence at different lumbar levels in both stenosis and nonstenosis groups. In addition, a two-way analysis of variance (ANOVA) was used to determine the association between body mass index (BMI) and FJ arthrosis. Results. The rate of FJ arthrosis at L3–L4 and L4–L5 were significantly higher (P < 0.001) in the stenotic group compared to the control. In the control group the prevalence of FJ arthrosis increases cephalocaudally (L3-L4 = 16%, L4–L5 = 28%, L5–S1 = 55%), whereas in the stenotic group there is a sharp increase from L3–L4 (27%) to L4–L5 (58%), but not from L4–L5 to L5–S1 (55%). No association between FJ arthrosis and sex was noted. Although, mean BMI was significantly smaller in the control group compared to the stenotic group, no association between BMI and facet arthrosis was found. In the general population the prevalence of FJ arthrosis at all three levels was greater for the right side; however, significant difference (P = 0.004) was obtained only for L3–L4. In all joints studied, the prevalence of FJ arthrosis increases considerably from the young age cohort (18–39) to the old age cohort (>60). Nevertheless, 10% of the young individuals (18–39) have already manifested FJ arthrosis at L5–S1. No arthrosis at that age was observed at L3–L4. Conclusion. FJ arthrosis is an age-dependent and BMI and sex independent phenomenon. In the general population, the prevalence of FJ arthrosis increases cephalocaudally with the highest frequency at L5–S1. In the stenotic group, the highest frequency was observed at the two caudal levels; L4–L5 and L5–S1. The prevalence of FJ arthrosis was greater for the right side.

Hyperostosis frontalis interna: criteria for sexing and aging a skeleton

Estimation of sex and age in skeletons is essential in anthropological and forensic medicine investigations. The aim of the current study was to examine the potential of hyperostosis frontalis interna (HFI) as a criterion for determining sex and age in forensic cases. Macroscopic examination of the inner aspect of the frontal bone of 768 skulls (326 males and 442 females) aged 1 to 103, which had undergone a head computerized tomography scan, was carried out using the volume rendering technique. HFI was divided into two categories: minor and major. HFI is a sex- and age-dependent phenomena, with females manifesting significantly higher prevalence than males (p < 0.01). In both females and males, prevalence of HFI increases as age increases (p < 0.01). We present herein the probabilities of designating an unknown skull to a specific sex and age cohort according to the presence of HFI (standardized to age distribution in an Israeli population). Moreover, we present the probability of an individual belonging to a specific sex or age cohort according to age or sex (respectively) and severity of HFI. We suggest a valid, reliable, and easy method for sex and age identification of unknown skulls.

Vertebral Hemangiomas and Their Correlation With Other Pathologies.

Study Design. This cross-sectional study was carried out on 196 adults (98 men and 98 women), aged between 18 and 91 years. Objective. To examine whether vertebral hemangiomas (VHs) are associated with other spinal pathologies, metabolic diseases, cardiovascular diseases, cancer and past trauma, to shed light on their possible pathophysiology. Summary of Background Data. VHs are the most common form of benign tumors in the spine. Their association with spinal and systemic pathologies has not yet been systematically studied. Methods. Clinical data were gathered from full spine CT scans and medical records. Results. VHs were significantly associated with disc lesions (P = 0.004), past trauma (P = 0.037), diabetes (&khgr;2 = 5.179, P = 0.023), cardio-vascular diseases (&khgr;2 = 8.625, P = 0.003), and cancer (&khgr;2 = 5.820, P = 0.016), but not with obesity. Only medium-large size VHs were significantly associated with osteoporosis (&khgr;2 = 6.695, P = 0.010). Conclusion. The pattern of diseases related to VHs suggests a common cause for VH, namely, a disruption of vascular flow in the microvessels (accompanied by endothelium damage) within the vertebral body, eventually resulting in hypervascularization. Level of Evidence: 4

Hyperostotic bone disease in a wombat (Vombatus ursinus)

Little is known about wombat diseases in general, and about their congenital diseases in particular. In the current study, the skeleton of a common wombat (Vombatus ursinus) that exhibited generalized hyperostosis is analyzed, and possible diagnoses are reviewed. Macromorphological analyses revealed that the diaphyses of the long bones manifested an increased diameter with extensive diaphyseal new-bone formation (periosteal and endosteal). Cross-sections of the diaphyses showed that the cortical-medullary demarcation was indistinct. The calvarial bones were thickened. Radiographs showed uniform sclerosis of the long bones with loss of trabecular pattern. Microradiography showed extensive bone remodeling, a hyper-vascularized lamellated layer of bone and numerous linear formation defects. Possible causes for the lesions, including sclerosing bone dysplasia disorders, acquired syndromes causing hyperostosis, and metabolic diseases typical of animals in captivity, are discussed.