Publications by authors named "Alison I Bernstein"
Article Synopsis
- The study investigates the role of 5-hydroxymethylcytosine (5hmC) in Parkinson's disease (PD), emphasizing its importance in the brain and its potential link to neurotoxic responses.
- Researchers identified 1,030 interaction differentially modified cytosines (iDMCs) that exhibit paired changes in 5hmC and 5-methylcytosine (5mC), mapping to 695 genes relevant to PD, including genes previously implicated in the disease.
- The findings suggest that these epigenetic changes could contribute to the development of idiopathic PD, with many identified genes also playing roles in synaptic functions.
Article Synopsis
- * Researchers found that dieldrin exposure caused sex-specific changes in DNA modifications related to the development of dopaminergic neurons over different ages, indicating critical periods of neurodevelopment were affected.
- * The findings suggest that these persistent epigenetic changes may contribute to differences in PD risk between sexes, emphasizing the long-term impacts of developmental exposure to dieldrin on brain health.
Article Synopsis
- Epidemiological and animal studies indicate that exposure to the pesticide dieldrin is linked to a higher risk of developing Parkinson's disease (PD), particularly through developmental exposure impacting neuronal susceptibility.
- The research reveals sex-specific DNA modifications related to dopaminergic neuron development following dieldrin exposure, observed at various age points from birth to 36 weeks.
- Findings suggest that these lasting epigenetic changes may interfere with key neurodevelopmental processes, potentially increasing the risk for late-onset diseases like PD.
Article Synopsis
- Environmental risk factors and gene-environment interactions are crucial in the development of Parkinson's disease (PD), but these factors have often been overlooked.
- A proposed "PD prevention agenda" emphasizes the need for research to focus on modifying environmental risks and includes calls for advanced studies in transcriptomics and epigenomics.
- The emerging field of epitranscriptomics could further illuminate how gene and environmental factors interact in PD, unveiling potential biomarkers and prevention strategies through recent technological innovations.
Article Synopsis
- - Understanding the early phases of synucleinopathy, particularly before neurodegeneration occurs, is crucial for developing therapies and studying disease progression, as shown in a rat model that mimics Parkinson's disease pathology.
- - In the study, researchers utilized laser capture microdissection and RNA sequencing to identify transcriptional changes in the substantia nigra, revealing that immune response-related transcripts increase while neurotransmission and dopamine pathway-related transcripts decrease during early synucleinopathy.
- - Verification of 29 specific transcripts associated with neurotransmission and dopamine pathways was conducted and findings indicated that decreases in transcripts like Syt1 and Slc6a3 were present in neurons with pSyn inclusions, shedding light on the molecular mechanisms that may drive
Article Synopsis
- Parkinson's disease (PD) is rapidly increasing globally, especially in industrialized regions, indicating potential environmental influences, specifically from pollutants like dieldrin, a pesticide.
- Research on mice reveals that exposure to dieldrin during development makes them more vulnerable to neuron damage and motor function deficits when exposed to α-synuclein, a protein linked to PD.
- The study shows that while dieldrin exposure increases dopamine release in certain brain areas affected by α-synuclein, it doesn't change VMAT2 activity, suggesting that early exposure to dieldrin may heighten the brain's response to neurodegeneration without obvious signs of damage.
Article Synopsis
- Evidence is increasing that epigenetic regulation, particularly DNA methylation, contributes to the development of Parkinson's disease (PD), which is influenced by age, genetics, and the environment.
- Current studies have limitations, as they often overlook the impacts of cell type and sex, which are important given the diverse nature of brain tissue and known gender differences in PD outcomes.
- A new genome-wide analysis focusing on enriched neuronal populations from PD brains revealed sex-specific methylation changes in several critical genes related to brain development and neurotransmitter functions.
Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits.
Aysegul O Gezer Joseph Kochmanski Sarah E VanOeveren Allyson Cole-Strauss Christopher J Kemp Alison I Bernstein
Neurobiol Dis
July 2020
Article Synopsis
- Exposure to the pesticide dieldrin is linked to a higher risk of Parkinson's disease (PD), and previous studies indicated that it makes neurons more sensitive to toxic substances like MPTP in mice.
- This study used a new model involving α-synuclein pre-formed fibrils (PFFs) to see if dieldrin exposure during development raises vulnerability to PD-like conditions.
- Results showed that male mice exposed to dieldrin had worsened motor skills and increased dopamine turnover after PFF exposure, but didn't show increased aggregation of α-synuclein or loss of certain neurons, highlighting a male-specific response to dieldrin's effects on neurotoxicity.
The Impact of Environmental Factors on 5-Hydroxymethylcytosine in the Brain.
Curr Environ Health Rep
June 2020
Article Synopsis
- * New research links factors like chemicals, stress, diet, and exercise to variations in 5-hmC, but methods used lack specificity, making it hard to see if these changes impact specific biological pathways.
- * To better understand how environment influences 5-hmC and its role in neurological diseases, the field of neuroepigenetics needs to adopt more precise measurement tools.
Article Synopsis
- Epigenetic marks like 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) play crucial roles in regulating gene expression at various chromosomal levels, particularly in the brain.
- Traditional methods for measuring these marks often fail to distinguish between them, leading to gaps in understanding their unique functions in research.
- A new statistical modeling approach has been proposed to analyze both 5-mC and 5-hmC data simultaneously, showing improved detection of changes related to Alzheimer's disease compared to traditional methods.
Article Synopsis
- Exposure to the pesticide dieldrin during development is linked to increased risk of Parkinson's disease (PD) in both humans and animals.
- A study on male and female C57BL/6 mice revealed that dieldrin exposure leads to changes in DNA methylation, affecting genes crucial for the health of dopamine-producing neurons.
- The findings highlight sex-specific effects of dieldrin on the epigenome, suggesting that these changes could increase vulnerability to neurodegenerative diseases later in life.
Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection.
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- * Genetic deletion of SV2C results in decreased dopamine release, impaired motor functions, and changes in nicotine's effects, highlighting its importance in dopamine homeostasis.
- * Altered SV2C levels are observed in postmortem tissues of PD patients, distinguishing it from other neurodegenerative diseases, suggesting its disruption is significant in understanding PD-related dopaminergic dysfunction.
Article Synopsis
- VMAT2 is a crucial transporter protein that packages important neurotransmitters like dopamine and serotonin into vesicles for release in the brain, and its function is linked to conditions like oxidative stress and Parkinson's disease.
- Researchers developed a new rabbit polyclonal antibody specific to VMAT2 to address a shortage of existing antibodies, ensuring it recognizes and localizes the protein in synaptic vesicles.
- This novel antibody effectively demonstrates VMAT2's distribution across key brain regions involved in neurotransmission, making it a valuable tool for exploring neurodegenerative and neuropsychiatric disorders tied to vesicular issues.
Article Synopsis
- The vesicular monoamine transporter 2 (VMAT2) is crucial for packaging neurotransmitters and protecting neurons from toxicants.
- Mice with low levels of VMAT2 show symptoms similar to Parkinson's disease, while those with high levels are better protected against neuron damage.
- Research confirms that VMAT2 impacts dopamine release and handling, suggesting it plays a significant role in protecting dopamine neurons and might influence side effects of L-DOPA in Parkinson's treatments.
Article Synopsis
- - Alzheimer's disease (AD) is a progressive disorder affecting cognitive function, and recent research highlights the potential role of epigenetic regulation, particularly through the modifications of 5-methylcytosine and 5-hydroxymethylcytosine (5hmC), which are prominent in the nervous system.
- - A study analyzing DNA from the prefrontal cortex of post-mortem AD patients discovered 325 genes with differentially hydroxymethylated loci (DhMLs), linked to neuronal development and neurogenesis, suggesting these changes could impact gene expression related to AD.
- - By integrating epigenomic and transcriptomic data, along with confirmation from an AD model in fruit flies, researchers found connections between
Article Synopsis
- The study investigates the psychotropic effects of the sacred lotus (Nelumbo nucifera) and focuses on the alkaloid nuciferine, which shows potential similarities to antipsychotic drugs.
- Using in silico predictions and pharmacological assays, nuciferine was characterized in terms of its receptor interactions and effects on behavior in rodent models.
- The findings suggest that nuciferine displays atypical antipsychotic-like properties, sharing some similarities with existing antipsychotics but maintaining unique characteristics.
Article Synopsis
- Disruption in the dynamics of neurotransmitter vesicles is linked to various neurodegenerative and neuropsychiatric disorders, prompting the exploration of a new mouse model with enhanced vesicular function through VMAT2 overexpression.
- This model demonstrated significant improvements, including a 56% increase in dopamine transport capacity, a 21% rise in tissue dopamine levels, and an 84% boost in stimulated dopamine release, alongside enhanced locomotor activity and reduced anxiety/depressive behaviors.
- Additionally, these mice showed protection against neurotoxicity from MPTP, indicating that therapies aimed at boosting vesicular capacity may offer new treatment options for conditions like Parkinson's disease.
Article Synopsis
- Active transport of neurotransmitters into synaptic vesicles is crucial for the release of neurotransmitters, and is primarily facilitated by proteins called vesicular monoamine transporters (VMAT1 and VMAT2).
- These transporters are essential for packaging key neurotransmitters like dopamine, norepinephrine, serotonin, and histamine, which are vital for healthy brain function.
- There has been a lack of drugs that specifically target these vesicular proteins, largely due to challenges in testing and the complexity of their mechanisms; however, new compounds and methods are now emerging that could lead to effective screening and potential drug development targeting these transporters.
Article Synopsis
- Parkinson's disease (PD) is a common movement disorder with unclear causes, though environmental agents, particularly man-made chemicals, are suspected risk factors.
- Recent research using fruit flies (Drosophila melanogaster) shows that the volatile fungal compound 1-octen-3-ol can lower dopamine levels and damage dopamine neurons.
- The study indicates that 1-octen-3-ol disrupts dopamine balance, affecting both fruit flies and human cell lines, suggesting it might be a naturally occurring environmental factor linked to the development of PD.
Article Synopsis
- The main issue in Parkinson's disease (PD) involves dopamine (DA) neurotransmission, which is crucial for proper motor control and is heavily dependent on the storage and release of dopamine in vesicles.
- When vesicular function is disrupted, it leads to an increased risk of damage to dopamine-producing neurons, potentially worsening the symptoms of PD.
- This review discusses various factors that can disturb dopamine vesicle function and suggests that improving vesicular function could be a promising treatment approach for managing PD.
Article Synopsis
- Parkinson's disease (PD) involves the loss of dopamine-producing neurons in the brain, leading to symptoms like tremors and rigidity; exposure to the neurotoxin MPTP mimics these symptoms in animals by causing similar neuronal loss.
- Research showed that MPP(+) activates cellular stress responses, particularly the unfolded protein response (UPR), which is linked to cell death.
- The study found that the protein PUMA is crucial for MPP(+)-induced cell death, with evidence suggesting that both PUMA and p53 are necessary for this process, while ATF3 does not play a role.
Article Synopsis
- VMAT2 (vesicular monoamine transporter 2) is essential for packaging monoamines into synaptic vesicles, influencing disorders like Parkinson's and drug addiction.
- Researchers developed a modified Neurotransmitter Uptake Assay to measure VMAT2 function in live cells, which was previously challenging.
- The new assay was validated using HEK293 cell lines, confirming that it can visualize VMAT2 activity and assess the effects of specific inhibitors like tetrabenazine.
Article Synopsis
- Parkinson's disease (PD) is marked by the loss of dopaminergic neurons, leading to common symptoms like tremors and rigidity, and 6-hydroxydopamine (6-OHDA) mimics these symptoms while activating cellular stress pathways.
- Research indicates that the BH3-only protein, Puma, plays a critical role in 6-OHDA-induced cell death in dopaminergic neurons, and experiments with wild-type and Puma-null mice confirm this necessity.
- Findings suggest that the DNA damage response and p53 are crucial for cell death caused by 6-OHDA, showing that Puma's role in this process is separate from the usual unfolded protein response (UPR) pathways.