Social adversity in pregnancy and trajectories of women's depressive symptoms: A longitudinal study.

BACKGROUND: Sound evidence has linked the experience of adversity with depression. Less is known about this association over time. AIM: The aim of this study is to determine whether or not social adversity experienced by pregnant women is associated with their patterns of depressive symptoms over their reproductive life course. METHODS: Data were obtained from a cohort of women collected at their first obstetrical clinic visit of an index pregnancy (time-point 1) and at a further six time-points to 27 years following the birth. Latent Class Growth Modelling was used to estimate trajectories of women's depressive symptoms over this time period. Logistic regression modelling determined the prospective association between measures of adversity in pregnancy and 27-year postpartum depression trajectories, controlling for potential confounders. FINDINGS: Experiencing financial problems, housing problems, serious disagreements with partners and with others, and experiencing serious health problems in pregnancy were associated with membership of high and middle depression trajectories over the 27 years. Having someone close die or have a serious illness was associated with the high depression trajectory only. Younger maternal age and low family-income at first clinic visit were also associated with an increased risk of women's membership of both high and middle depression trajectories. CONCLUSIONS: Experiencing adversity during pregnancy predicts subsequent patterns of maternal depression over an extended period of women's reproductive life course. It is not clear whether women's experiences of adversity during pregnancy were causally associated with subsequent depression or whether there are other explanations of the observed association.

Does having a difficult child lead to poor maternal mental health?

OBJECTIVES: Considerable evidence suggests maternal psychopathology influences that of their offspring. The probability of a reverse causal pathway has been only rarely considered but is a concern, given around 10% of children manifest mental impairment during their early years. This study determines the extent to which child behavior problems at ages 5 and 14 years are associated with mothers' mental health at 21 years post birth. STUDY DESIGN: Longitudinal study. METHODS: Data were taken from a sample of 3650 women from Mater and University of Queensland Study of Pregnancy birth cohort. Women's mental health was measured using the Mental Disorder Screening Tool at 21 years post birth. The Child Behavior Check List was used to measure internalizing, combined social/attention/thought disorder, and aggression at the age of 5 and 14 years. Logistic regression was used to derive odds ratios and 95% confidence intervals. A number of confounders were used to test for independence. RESULTS: Following all adjustments, child internalizing behaviors and combined social/attention/thought disorder at 5 years, and all measures of child behavior problem at 14 years were associated with mothers meeting criteria for mental health impairment at 21 years post birth. Moreover mothers of children with behavior problems at 14 years were approximately 2-3 times more likely to these meet these criteria. CONCLUSIONS: Mothers of children with behavior problems at 5 and 14 years of age were more likely to have mental health impairment at 21 years post birth. Child health professionals should be cognizant of the mother-child relationship having mutual mental health vulnerability.

How have the lives of pregnant women changed in the last 30 years?

BACKGROUND: To what extent have the characteristics and needs of pregnant women changed over time? This cross-sectional, comparative study describes some socio-demographic, mental health and lifestyle characteristics of two samples of pregnant women assessed 30 years apart. METHODS: We recruited two samples of pregnant women who were attending their first clinic visit at the same large Queensland maternity hospital 30 years apart between 1981 to 1984 (Sample A, N=6753) and 2011-2012 (Sample B, N=2156). The women were compared using the same survey tool. Descriptive statistics are presented. Pearson's chi-square tests were undertaken (significance at <0.05) to determine how the characteristics and needs of pregnant women may be changing over time. FINDINGS: Women, recently sampled, were older, more highly-educated and were more likely to be living with, but not married to, their partners, as well as having their first baby, than were women 30 years ago. As well, recently sampled, pregnant women were more likely to be non-smokers, to have higher body mass indexes and more symptoms of anxiety, but were less likely to be having an unplanned pregnancy. CONCLUSION: This study found a number of differences between the socio-demographic characteristics, lifestyles and mental health of two samples of pregnant women assessed 30 years apart. Our findings suggest the need for ongoing monitoring of pregnant women to determine changing health priorities. Being more educated, today's women may be more amenable to health education interventions. Higher body mass indexes for recently sampled women, highlights an emerging problem that needs to be addressed.

Trajectories and predictors of women's depression following the birth of an infant to 21 years: a longitudinal study.

Little is known about the long-term mental health of women following the birth of an infant. This study describes the 21 year trajectory of women's depression following the birth of an infant and identifies early predictors of post-birth maternal depression trajectories. The sample comprises 2,991 women from the Mater and University of Queensland Study of Pregnancy. Using the Delusions-Symptoms-States-Inventory, depression was measured at 6 months, 5, 14 and 21 years after the birth. These measures were clustered and in addition bivariate and multivariate analyses were used to test for significant association between the groups and a range of maternal socio-demographic, psychological and pregnancy-related factors. Two depression trajectories were produced, a no-low depression group (79.0 %) and a high-escalating depression group (21.0 %). The strongest predictors for a high-escalating depression group were conflict in the partner-relationship (p < 0.001), anxiety (p < 0.001) and stress (p < 0.001) in the antenatal period, having many pregnancy symptoms (p < 0.001), being younger (p < 0.001) and having poorer social networks (p < 0.001). To a lesser extent not completing high school (p < 0.05), being unsure about wanting the pregnancy (p < 0.05) and not wanting contact with the infant following the birth (p < 0.05) were also predictors for high-escalating depression trajectory. Our findings suggest a sub-sample of mothers experience persistent depressive symptoms over a 21 year period following the birth of their infant. Partner conflict, inadequate social supports and poor mental health during the pregnancy, rather than factors relating to the birth event, contribute to women's depressive symptoms in the long-term. Given the identification of early markers for persistent depression, there may be opportunities for intervention for at-risk pregnant women.

Women's frequency of alcohol consumption prior to pregnancy and at their pregnancy-booking visit 2001-2006: A cohort study.

BACKGROUND: With evidence of offspring harms and concern for younger women's drinking behaviours, this study uses a hospital cohort to trend the use and changes in women's reported alcohol consumption. AIMS: To examine (i) the trend of women's reported alcohol consumption over time, (ii) whether any increases in the frequency of alcohol consumption prior to a pregnancy are accompanied by increases in the frequency of alcohol consumption in pregnancy and (iii) the characteristics of women consuming alcohol at these times. METHODS: Midwives collected routine data on 19,699 women between 2001 and 2006. Data on women's alcohol use prior to pregnancy and at their pregnancy-booking visit were analysed using a non-parametric test for trend and with bivariate and multivariate tests adjusting for possible confounders. FINDINGS: The proportion of women reporting at-least weekly alcohol use prior to pregnancy was 25.4% and 5.9% at their pregnancy-booking visit. A significant linear increase over time (p<0.001) was found in the rate of women aged 20 years and older reporting at-least weekly alcohol use prior to pregnancy. Tertiary-educated women were more likely to consume alcohol at-least weekly prior to pregnancy. Women aged less than 20 years were less likely to report at-least weekly alcohol use at both time points. Having more children and Asian ethnicity were associated with a lower risk of at-least weekly alcohol use at these times. CONCLUSION: The majority of women reduce their alcohol consumption once they learn they are pregnant, with some evidence this trend may have increased in recent years.

Birth outcomes associated with cannabis use before and during pregnancy.

INTRODUCTION: This study aimed to examine the association between cannabis use before and during pregnancy and birth outcomes. RESULTS: Overall, 26.3% of women reported previous use of cannabis and 2.6% reported current use. Multivariate analysis, controlling for potential confounders, including tobacco smoking, alcohol consumption, and use of other illicit drugs, showed that cannabis use in pregnancy was associated with low birth weight (odds ratio (OR) = 1.7; 95% confidence interval (CI): 1.3-2.2), preterm labor (OR = 1.5; 95% CI: 1.1-1.9), small for gestational age (OR = 2.2; 95% CI: 1.8-2.7), and admission to the neonatal intensive care unit (OR = 2.0; 95% CI: 1.7-2.4). DISCUSSION: The results of this study show that the use of cannabis in pregnancy is associated with increased risk of adverse birth outcomes. Prevention programs that address cannabis use during pregnancy are needed. METHODS: Data were from women birthing at the Mater Mothers' Hospital in Brisbane, Australia, over a 7-y period (2000-2006). Women were interviewed in the initial antenatal visit about their use of cannabis and other substances. Records for 24,874 women who provided information about cannabis use, and for whom birth outcomes data were available, were included in the analysis.

Illicit drug use before and during pregnancy at a tertiary maternity hospital 2000-2006.

INTRODUCTION AND AIMS: To study the prevalence of use of illicit drugs by women of reproductive age before and during pregnancy and the changes in rates of illicit drug use in pregnancy over recent years. DESIGN AND METHODS: All pregnant women attending the public antenatal clinic over a 7 year period (2000-2006) were routinely interviewed about their use of illicit drugs by a midwife at the antenatal booking visit. MEASUREMENTS: Records for 25,049 women, who self-reported previous and current use of cannabis, amphetamines, ecstasy and heroin, were included in the study. RESULTS: Cannabis was the most common illicit drug used before and during pregnancy; 9.3% of women were engaged in regular use prior to pregnancy and 2.5% were users during pregnancy. A very low proportion of women reported use of amphetamines, ecstasy or heroin in pregnancy. There was an increase in ever regular use and any past use of cannabis, amphetamines and ecstasy over time. CONCLUSIONS: The prevalence of illicit drug use by young women prior to becoming pregnant is of concern. While pregnancy appears to be a strong motivator for women to cease substance use, there is a need to study whether women resume drug use after their baby is born.

Brain stem pathology in Parkinson's disease: an evaluation of the Braak staging model.

The lower brain stem of 25 pathologically-confirmed Parkinson's disease (PD) cases was examined by alpha synuclein immunohistochemistry to characterize pathological accumulation of alpha synuclein (Lewy-type α-synucleinopathy, LTS) in the medulla oblongata, to examine differences between affected regions and test a proposed model of staging of pathology in PD. All cases had LTS in the medulla, including the dorsal motor nucleus of the vagus (dmX), when present. The distribution followed a consistent pattern and appeared to be concentrated in a tyrosine hydroxylase (TH) immunoreactive region, probably representing the dorsal IX/X nuclear complex and the intermediate reticular zone. LTS density was greatest in the dmX. A similar distribution pattern to PD was seen in 14 incidental Lewy body disease (ILBD) cases, five derived from the Queen Square Brain Bank tissue collection and nine identified in separate series of 60 neurologically-normal individuals, and in three cases with the G2019S mutation of LRRK2. Semiquantitative assessment showed that severity of pathology in the dmX was not correlated with the severity of cortical pathology. Semiquantitative assay of TH and ChAT peptide expression in the medulla showed that TH expression in PD and ILBD did not differ from controls. These findings broadly support the Braak hypothesis of caudo-rostral development but indicate that the extent of the disease in the cortex and the severity of pathology in the medulla were independent of one another.

Hyposmia in progressive supranuclear palsy.

Previous studies suggested that olfaction is normal in progressive supranuclear palsy (PSP). We applied the University of Pennsylvania Smell Identification Test (UPSIT) to 36 patients with PSP who scored more than 18 on the Mini Mental State Examination (MMSE), 140 patients with nondemented Parkinson's disease (PD) and 126 controls. Mean UPSIT scores in PSP were lower than in controls (P < 0.001) but higher than in PD (P < 0.001) after adjusting for age, gender, and smoking history. For patients with PSP, UPSIT scores correlated with MMSE (r = 0.44, P = 0.006) but not disease duration (P = 0.6), motor subscale of the Unified Parkinson's Disease Rating Scale (P = 0.2), or Frontal Assessment Battery (P = 0.5). The brains of six of the patients with PSP were examined postmortem and all revealed neurofibrillary tangles and tau accumulation in the rhinencephalon, although only three had hyposmia. Further prospective studies including patients with early PSP and PSP-P with postmortem confirmation might help clarify if smell tests could be useful when the differential diagnosis lies between PD and PSP.

Regional differences in the severity of Lewy body pathology across the olfactory cortex.

We studied alpha-synuclein pathology in the rhinencephalon of ten cases of Parkinson's disease (PD) and twelve neurologically normal controls, of which seven had incidental Lewy bodies in the substantia nigra at autopsy and five had no pathological evidence of neurological disease. In all PD and incidental Lewy bodies cases, alpha-synuclein pathology was found in all five subregions of the primary olfactory cortex that were sampled, and amongst them the pathology was significantly more severe in the temporal division of the piriform cortex than in the frontal division of the piriform cortex, olfactory tubercle or anterior portions of the entorhinal cortex. The orbitofrontal cortex, which is an area of projection from the primary olfactory cortex, was affected in some cases but overall the alpha-synuclein pathology was less severe in this area than in the primary olfactory cortex. Because different areas of the rhinencephalon are likely to play different roles in olfaction and our data indicate a differential involvement by alpha-synuclein deposition of structures implicated in smell, future prospective studies investigating the pathophysiological basis of hyposmia in PD should consider to examine the areas of primary olfactory cortex separately.

The CRF-like peptide urocortin greatly attenuates loss of extracellular striatal dopamine in rat models of Parkinson's disease by activating CRF(1) receptors.

We have recently observed that the corticotrophin releasing factor (CRF) related peptide urocortin reverses key features of nigrostriatal damage in two paradigms of Parkinson's disease. Here we have studied whether these effects are supported by a retention of striatal basal and evoked extracellular dopamine and the receptor(s) that may mediate this effect. Fourteen days following stereotaxic injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) and urocortin, extracellular dopamine levels in striata ipsilateral to injection sites of 6-OHDA/LPS and urocortin treated rats were comparable with sham injected rats, whilst rats given 6-OHDA/LPS and vehicle had considerably lower dopamine levels. Striatal dopamine levels in animals where urocortin injection was delayed by seven days were only modestly decreased compared to animals receiving 6-OHDA/LPS and urocortin concomitantly. Additionally, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also preserved in dialysates from urocortin treated rats. The effects of urocortin were entirely blocked by the non-selective CRF receptor antagonist alpha-helical CRF as well as the selective CRF(1) antagonist NBI 27914 and were not replicated by the selective CRF(2) ligand urocortin III. In the substantia nigra tissue dopamine changes mirrored those seen in striatal extracellular dopamine. Our data strongly suggest that urocortin is capable of maintaining adequate nigrostriatal function in vivo via CRF(1) receptors following. neurotoxic challenge.

Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease.

BACKGROUND: It has recently become apparent that neuroinflammation may play a significant role in Parkinson's disease (PD). This is also the case in animal paradigms of the disease. The potential neuroprotective action of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 (EX-4), which is protective against cytokine mediated apoptosis and may stimulate neurogenesis, was investigated In paradigms of PD. METHODS: Two rodent 'models' of PD, 6-hydroxydopamine (6-OHDA) and lipopolysaccaride (LPS), were used to test the effects of EX-4. Rats were then investigated in vivo and ex vivo with a wide range of behavioural, neurochemical and histological tests to measure integrity of the nigrostriatal system. RESULTS: EX-4 (0.1 and 0.5 mug/kg) was given seven days after intracerebral toxin injection. Seven days later circling behaviour was measured following apomorphine challenge. Circling was significantly lower in rats given EX-4 at both doses compared to animals given 6-OHDA/LPS and vehicle. Consistent with these observations, striatal tissue DA concentrations were markedly higher in 6-OHDA/LPS + EX-4 treated rats versus 6-OHDA/LPS + vehicle groups, whilst assay of L-DOPA production by tyrosine hydroxylase was greatly reduced in the striata of 6-OHDA/LPS + vehicle rats, but this was not the case in rats co-administered EX-4. Furthermore nigral TH staining recorded in 6-OHDA/LPS + vehicle treated animals was markedly lower than in sham-operated or EX-4 treated rats. Finally, EX-4 clearly reversed the loss of extracellular DA in the striata of toxin lesioned freely moving rats. CONCLUSION: The apparent ability of EX-4 to arrest progression of, or even reverse nigral lesions once established, suggests that pharmacological manipulation of the GLP-1 receptor system could have substantial therapeutic utility in PD. Critically, in contrast to other peptide agents that have been demonstrated to possess neuroprotective properties in pre-clinical models of PD, EX-4 is in current clinical use in the management of type-II diabetes and freely crosses the blood brain barrier; hence, assessment of the clinical efficacy of EX-4 in patients with PD could be pursued without delay.

The CRF-like peptide urocortin produces a long-lasting recovery in rats made hemiparkinsonian by 6-hydroxydopamine or lipopolysaccharide.

We have recently observed that the corticotropin releasing factor related peptide urocortin (UCN) reverses key features of nigrostriatal neurodegeneration following intracerebral injection of either 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS). To determine the potential therapeutic utility of UCN here we have studied whether these effects are sustained for several weeks following peptide injection. In addition we have studied whether UCN still shows efficacy in rats with more pronounced nigrostriatal lesions. Rats were lesioned using 6-OHDA or LPS and injected with UCN either 7 or 14 days later. At different time points animals were tested for rotational behaviour (apomorphine, 0.5 mg/kg) and subsequently implanted with bilateral dialysis probes into the striata. The following day rats were dialysed to estimate extracellular striatal dopamine (DA) and then sacrificed for estimation of striatal tissue DA and subsequent immunohistochemistry of TH(+) cells in the substantia nigra (SN). Toxin treated rats given UCN 7 days later showed clear evidence of reduced nigrostriatal damage both 28 and 84 days following UCN compared with saline injection. In rats given UCN 14 days after toxin injection, by which time deficits were maximal, a restoration of nigrostriatal damage was observed. This suggests that UCN is able to elicit a sustained restoration of functional nigrostriatal integrity and has the ability to produce a recovery in severely lesioned rats. These findings suggest that stimulation of CRF (probably CRF(1)) receptors could have therapeutic utility in PD.

DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders.

Mutations in the DJ-1 gene are associated with autosomal recessive Parkinson's disease (PD), but its role in disease pathogenesis is unknown. This study examines DJ-1 immunoreactivity (DJ-1 IR) in a variety of neurodegenerative disorders, Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with Pick bodies, FTLD with MAPT mutations, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), in which hyperphosphorylated tau inclusions are the major pathological signature. DJ-1 IR was seen in a subset of neurofibrillary tangles (NFTs), neuropil threads (NTs), and neurites in extracellular plaques in AD; tau inclusions in AD contained both 3R and 4R tau. A subset of Pick bodies in FTLD showed DJ-1 IR. In PSP, DJ-1 IR was present in a few NFTs, NTs and glial cell inclusions. In CBD, DJ-1 IR was seen only in astrocytic plaques. In cases of FTLD with MAPT mutations that were 4R tau positive (i.e. N279K and exon 10+16 mutations), DJ-1 IR was present mostly in oligodendroglial coiled bodies. However, in MAPT R406W mutation cases, DJ-1 IR was associated mainly with NFTs and NTs and these were both 3R and 4R tau positive. No DJ-1 IR was present in FTLD with ubiquitin inclusions (FTLD-U). In AD and FTLD with Pick bodies, DJ-1 protein was enriched in the sarkosyl-insoluble fractions of frozen brain tissue containing insoluble hyperphosphorylated tau, thus strengthening the association of DJ-1 with tau pathology. Additionally using two-dimensional gel electrophoresis, we demonstrated accumulation of acidic pI isoforms of DJ-1 in AD brain, which may compromise its normal function. Our observations confirm previous findings that DJ-1 is present in a subpopulation of glial and neuronal tau inclusions in tau diseases and associated with both 3R and 4R tau isoforms.

The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease.

The potential neuroprotective action of the corticotrophin-releasing factor-related peptide urocortin (UCN) was investigated in the rat 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) paradigms of Parkinson's disease. UCN (20 fmol) was either given at the same time as (T = 0) or 7 days after (T = +7) intracerebral 6-OHDA or LPS injection. At 14 days after 6-OHDA or LPS injection, circling behaviour was measured following apomorphine challenge. Circling was significantly lower in rats given UCN at either T = 0 or T = +7 compared with animals given 6-OHDA or LPS and vehicle. Sham-treated rats showed no circling. Consistent with these observations, striatal dopamine concentrations were markedly higher in 6-OHDA/LPS + UCN rats vs. 6-OHDA/LPS + vehicle groups. Additionally, L-dihydroxyphenylalanine production by tyrosine hydroxylase was greatly reduced in the striata of 6-OHDA/LPS + vehicle rats, whereas this was not the case in rats coadministered UCN. Finally, the numbers of tyrosine hydroxylase-positive cells recorded in the substantia nigra of 6-OHDA/LPS + vehicle-treated animals were markedly lower than those of sham-operated or 6-OHDA/LPS + UCN rats. Critically, UCN was effective in reversing lesion-induced deficits when given either at the same time as or 7 days after the neurotoxic insult. To our knowledge, this is the first time that such an effect has been demonstrated in vivo. The apparent ability of UCN to arrest the progression of or even reverse nigral lesions once established suggests that pharmacological manipulation of this system could have substantial therapeutic utility.

Striatal dopaminergic neurons are lost with Parkinson's disease progression.

Increased numbers of dopaminergic neurons are described in the striatum of patients with Parkinson's disease. In postmortem striatal tissue from Parkinson's disease patients with short disease duration (< or =8 years), the number of dopaminergic neurons is approximately four times that in patients with long duration (> or =16 years). The data suggest the possibility that the presence of large numbers of these striatal dopaminergic neurons may be harmful and may accelerate the disease process. Alternatively, these neurons may be lost to the disease process.

Kinase activity is required for the toxic effects of mutant LRRK2/dardarin.

Mutations in the LRRK2 gene, coding for dardarin, cause dominantly inherited Parkinson's disease (PD). Dardarin is a large protein, and mutations are found throughout the gene including the kinase domain. However, it is not clear if kinase activity is important for the damaging effects of pathogenic mutations. In this study, we noted two cellular phenotypes associated with mutant dardarin. First, pathogenic mutations increase the tendency of dardarin to form inclusion bodies. Secondly, neurons and neuronal cell lines undergo cell death after expression of mutant protein. Manipulating activity by replacing the kinase domain with a 'kinase-dead' version blocks inclusion body formation and strongly delays cell death. This predicts that kinase inhibitors will be useful therapeutic agents in patients with LRRK2 mutations and, perhaps, in sporadic PD. We also show that dardarin protein is expressed within human midbrain neurons and that C-terminal epitopes are also found in some Lewy bodies.

Melanized nigral neuronal numbers in Nigerian and British individuals.

The role of genetic and environmental factors in etiopathogenesis of Parkinson's disease (PD) is debated. The prevalence of PD is higher among white than nonwhite populations, yet it is five times higher in nonwhites living in the United States than in Nigeria. We compare counts of melanized nigral neurons between neurologically normal Nigerians and British brains. Neuronal counts were estimated in an age-matched sample of 23 Nigerian and 7 British brains from neurologically normal individuals who had no Lewy bodies and Lewy neurites on alpha-synuclein immunostaining. Two investigators blind to age and ethnicity performed counts of melanized neurons in a single 7-mum hemisections showing the substantia nigra pars compacta. No significant difference exits in the number of neurons between the Nigerian and the British subjects (P = 0.1, NS). Differences in melanized nigral neuronal numbers may not explain differences in the prevalence of PD between white and nonwhite populations, suggesting factors other than neuronal numbers contribute to differential susceptibility of black vs. white races to PD.

Development, characterisation and epitope mapping of novel monoclonal antibodies for DJ-1 (PARK7) protein.

Mutations in DJ-1 (PARK7) were recently identified as the cause for an autosomal recessive early onset form of familial Parkinson's disease, however, the function of the protein in the brain is yet to be elucidated. Here we report on the development, characterisation and epitope mapping, of two novel monoclonal antibodies to DJ-1. One of them (DJ-1 "clone16") has its epitope between amino acids 56-78 of the human DJ-1 protein and has very similar properties to a commercially available DJ-1 antibody clone 3E8. The second antibody recognised both the rat and human DJ-1 (DJ-1 "clone 48") and its epitope is between amino acids 26-56. We have used immunohistochemistry with these two antibodies to compare the distribution of DJ-1 in human and rat brain tissue. Both antibodies gave similar patterns of labelling in human brain with marked astrocytic expression. Neuronal labelling was weak or absent and the antibodies did not label Lewy bodies or Lewy neurites. In the rat brain, DJ-1 was ubiquitously expressed in neurones but exhibited low expression in astrocytes. These antibodies could be exploited as important tools in dissecting out DJ-1 expression in different species and examination of the role of DJ-1 in Parkinson's disease.

Synphilin-1 and parkin show overlapping expression patterns in human brain and form aggresomes in response to proteasomal inhibition.

Lewy bodies (LBs) are the characteristic inclusions of Parkinson's disease brain but the mechanism responsible for their formation is obscure. Lewy bodies (LBs) are composed of a number of proteins of which alpha-synuclein (alpha-SYN) is a major constituent. In this study, we have investigated the distribution patterns of synphilin-1 and parkin proteins in control and sporadic PD brain tissue by immunohistochemistry (IH), immunoblotting, and immunoelectron microscopy (IEM). We demonstrate the presence of synphilin-1 and parkin in the central core of a majority of LBs using IH and IEM. Using IH, we show an overlapping distribution profile of the two proteins in central neurons. Additionally, we show sensitivity of both endogenous synphilin-1 and parkin to proteolytic dysfunction and their co-localization in aggresomes formed in response to the proteasome inhibitor MG-132. We confirm that synphilin-1 and parkin are components of majority of LBs in Parkinson's disease and that both proteins are susceptible to proteasomal degradation.