T Cell Transcriptomes from Paroxysmal Nocturnal Hemoglobinuria Patients Reveal Novel Signaling Pathways.
Hosokawa K, Kajigaya S, Keyvanfar K, Qiao W, Xie Y, Townsley DM, Feng X, Young NS
This study found abnormal activity in key immune signaling pathways in T cells from people with PNH, a rare blood disorder. These changes may drive immune attacks on bone marrow stem cells and could lead to new treatments targeting the immune system.
- T cells in PNH show abnormal gene activity in immune pathways
- Specific genes like NR4A2 are dysregulated in PNH T cells
- These findings reveal new targets for treating immune-related bone marrow failure
- Pathways involved include TNFR, IGF1, and NOTCH signaling
- Results suggest immune modulation could be a treatment strategy
Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration and strength.
Ho ATV, Palla AR, Blake MR, Yucel ND, Wang YX, Magnusson KEG, Holbrook CA, Kraft PE, Delp SL, Blau HM
Prostaglandin E2 (PGE2) is crucial for muscle stem cells to repair damaged muscle, boosting regeneration and strength. Blocking PGE2—either genetically or through common painkillers like NSAIDs—hurts muscle recovery, while adding PGE2 can significantly improve healing.
- PGE2 helps muscle stem cells multiply and repair damage
- NSAIDs after injury can weaken muscle recovery
- PGE2 treatment speeds up muscle healing in experiments
- The EP4 receptor on stem cells is key to this process
- Boosting PGE2 may help treat muscle repair issues
Modulatory Role of Nurr1 Activation and Thrombin Inhibition in the Neuroprotective Effects of Dabigatran Etexilate in Rotenone-Induced Parkinson's Disease in Rats.
Kandil EA, Sayed RH, Ahmed LA, Abd El Fattah MA, El-Sayeh BM
Dabigatran etexilate protects dopamine-producing brain cells in a rat model of Parkinson's disease by boosting Nurr1 activity and reducing harmful clotting enzyme thrombin, leading to improved motor function and neuron survival.
- Dabigatran protects brain cells in Parkinson's model rats
- It increases Nurr1, a key protein for dopamine neurons
- It reduces thrombin, which harms neurons
- It lowers brain inflammation and restores dopamine
- Results suggest potential for repurposing dabigatran
Haploinsufficiency of NR4A2 is associated with a neurodevelopmental phenotype with prominent language impairment.
Reuter MS, Krumbiegel M, Schlüter G, Ekici AB, Reis A, Zweier C
A single copy of the NR4A2 gene is not enough to support normal brain development, leading to significant language delays and mild intellectual disability. This study confirms that losing one copy of NR4A2 causes a neurodevelopmental disorder, especially affecting speech and language.
- NR4A2 gene loss causes language and learning issues
- Only one functional copy of NR4A2 is insufficient
- Language problems are a core feature of this condition
- NR4A2 is vital for brain regions involved in speech
- De novo deletions in NR4A2 lead to clear symptoms
Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits.
Larson ME, Greimel SJ, Amar F, LaCroix M, Boyle G, Sherman MA, Schley H, Miel C, Schneider JA, Kayed R, Benfenati F, Lee MK, Bennett DA, Lesné SE
Oligomeric alpha-synuclein, a toxic form of the protein, reduces synapsin levels in the brain, which impairs memory. This effect occurs through suppression of genes that control synapsin production, involving key regulatory proteins like Nurr1.
- Toxic alpha-synuclein clumps lower synapsin levels
- Synapsin loss harms memory function
- Nurr1, a gene linked to NR4A2, is suppressed
- Alpha-synuclein oligomers disrupt gene regulation
- This mechanism may worsen neurological symptoms
Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population.
Ruiz-Sánchez E, Yescas P, Rodríguez-Violante M, Martínez-Rodríguez N, Díaz-López JN, Ochoa A, Valdes-Rojas SS, Magos-Rodríguez D, Rojas-Castañeda JC, Cervantes-Arriaga A, Canizales-Quinteros S, Rojas P
In a Mexican population, lower levels of NR4A2 gene expression and specific genetic variations in the NR4A2 gene are linked to a higher risk of Parkinson's disease. These findings suggest that NR4A2 may play a key role in the development of Parkinson's in this group.
- NR4A2 gene expression is reduced in Parkinson's patients
- Specific NR4A2 gene variants increase Parkinson's risk
- A genetic pattern combining two variants lowers gene activity
- These findings are specific to a Mexican population
- NR4A2 may be a key factor in Parkinson's development
Chiro-Optical Modulation for NURR1 Production from Stem Cells.
Patel M, Moon HJ, Hong JH, Jeong B
Exposing stem cells to L-polarized blue light boosts production of NURR1, a protein critical for dopamine neurons, and enhances markers of neuronal development. This light treatment also increases energy and calcium levels in cells, supporting their maturation into neurons.
- L-polarized blue light increases NURR1 in stem cells
- Neuronal markers rise at both RNA and protein levels
- Cell energy and calcium improve, aiding neuron development
- This method may help engineer cells for treating NURR1-related disorders
Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.
Montagud-Romero S, Nuñez C, Blanco-Gandia MC, Martínez-Laorden E, Aguilar MA, Navarro-Zaragoza J, Almela P, Milanés MV, Laorden ML, Miñarro J, Rodríguez-Arias M
This study found that adolescent and adult mice exposed to repeated social stress show increased sensitivity to cocaine's rewarding effects, with distinct changes in brain pathways involving dopamine and brain growth factors. Adolescents had lower stress hormone levels but reduced levels of a key dopamine gene (Pitx3), while adults showed reduced levels of a brain growth factor and its receptor. These differences suggest age-specific brain responses to stress and drug reward.
- Stress increases cocaine reward in both adolescent and adult mice
- Adolescents had lower stress hormones but less Pitx3 in dopamine brain area
- Adults had lower brain growth factor and receptor levels
- Different brain changes occur in adolescents vs. adults after stress
- These findings may inform how stress affects dopamine-related disorders
Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions.
Tong G, Meng Y, Hao S, Hu S, He Y, Yan W, Yang D
This study shows that parathyroid hormone (PTH) can activate a protein kinase C (PKC) pathway without using phospholipase C, instead relying on protein kinase A (PKA) to trigger PKC. This new signaling route may influence bone cell development and survival, with implications for how PTH works in bone health.
- PTH activates PKC through a PKA-dependent, PLC-independent route
- This pathway affects bone cell differentiation and reduces cell death
- The NR4A2 gene is regulated by this PTH signaling pathway
- PKA and PKC both play key roles in the process
- This mechanism may influence bone formation and repair
Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis.
Carter DA
This study identifies a temporary population of immature neurons in a specific brain region of young rats that produce the enzyme tyrosine hydroxylase but not dopamine, and shows these neurons lack key proteins like NR4A2/NURR1 that are essential for mature dopamine neuron function. The findings suggest that the absence of NR4A2/NURR1 may explain why these neurons do not fully mature or persist into adulthood.
- A temporary brain neuron group lacks NR4A2/NURR1 protein
- These neurons are immature and do not become true dopamine neurons
- NR4A2/NURR1 deficiency may block full maturation
- The neurons lose tyrosine hydroxylase expression over time
- This may mirror issues seen in NR4A2-related neurodevelopmental disorders
Dual delivery of siRNA and plasmid DNA using mesoporous silica nanoparticles to differentiate induced pluripotent stem cells into dopaminergic neurons.
Chang JH, Tsai PH, Chen W, Chiou SH, Mou CY
Using a special nanoparticle system, researchers successfully turned stem cells into dopamine-producing brain cells by delivering two key genetic instructions: one to boost the NURR1 protein and another to suppress a gene that blocks neuron development. This method produced over 88% dopamine-making neurons, which could help in studying and treating conditions like NR4A2-related syndrome.
- NURR1 gene delivery boosts dopamine neuron formation
- Combining gene activation with gene suppression improves results
- Over 88% of cells became dopamine-producing neurons
- Nanoparticles safely delivered genetic material without viruses
- Potential for developing therapies for NR4A2-related disorders
Region Specific Effects of Aging and the Nurr1-Null Heterozygous Genotype on Dopamine Neurotransmission.
Kummari E, Guo-Ross S, Eells JB
Mice with one copy of the Nurr1 gene missing show reduced dopamine levels in the brain's reward center, especially as they age, but not in movement-related areas. This suggests the brain's reward system is more vulnerable to both aging and Nurr1 deficiency than motor control circuits.
- Nurr1 deficiency worsens dopamine loss in the reward center with age
- Motor-related dopamine systems remain stable despite Nurr1 loss
- Stress increases activity in Nurr1-deficient mice
- Aging and genetics interact to affect dopamine health
- The reward system is more sensitive to Nurr1 changes than motor circuits
Developmental Vitamin D (DVD) Deficiency Reduces Nurr1 and TH Expression in Post-mitotic Dopamine Neurons in Rat Mesencephalon.
Luan W, Hammond LA, Cotter E, Osborne GW, Alexander SA, Nink V, Cui X, Eyles DW
Developmental vitamin D deficiency in rats disrupts the normal development of dopamine neurons by reducing Nurr1 and tyrosine hydroxylase expression, particularly in the substantia nigra, without changing neuron numbers. This suggests vitamin D is crucial for proper dopamine system maturation, which may contribute to schizophrenia risk.
- Vitamin D deficiency reduces Nurr1 in dopamine neurons
- TH levels drop specifically in the substantia nigra
- Neuron count and shape remain unchanged
- Early dopamine development is disrupted
- May explain dopamine-related behaviors in schizophrenia models
Nurr1:RXRα heterodimer activation as monotherapy for Parkinson's disease.
Spathis AD, Asvos X, Ziavra D, Karampelas T, Topouzis S, Cournia Z, Qing X, Alexakos P, Smits LM, Dalla C, Rideout HJ, Schwamborn JC, Tamvakopoulos C, Fokas D, Vassilatis DK
Activating the Nurr1:RXRα protein pair with a drug called BRF110 protects dopamine-producing brain cells and boosts dopamine levels in models of Parkinson's disease, improving symptoms without causing movement problems, suggesting it could be a single treatment that both protects the brain and relieves symptoms.
- BRF110 protects dopamine neurons from damage
- Increases dopamine production and levels in the brain
- Improves movement symptoms in Parkinson's models
- Does not cause dyskinesias with long-term use
- Targets Nurr1, a gene linked to neurodevelopment and Parkinson's
Possible genes responsible for developmental delay observed in patients with rare 2q23q24 microdeletion syndrome: Literature review and description of an additional patient.
Shimojima K, Okamoto N, Yamamoto T
Deletions in the 2q23q24 region are linked to developmental delay and language problems, with NR4A2 and GPD2 likely contributing to more severe symptoms when missing. Combining deletions of KCNJ3 and GPD2 may worsen developmental outcomes, suggesting these genes are key to the syndrome's severity.
- NR4A2 and GPD2 deletions may cause more severe developmental delay
- KCNJ3 may play a role in behavioral issues
- Combined loss of KCNJ3 and GPD2 leads to worse outcomes
- Deletion size affects symptom severity
- Further research needed to confirm gene roles
In vivo expression of Nurr1/Nr4a2a in developing retinal amacrine subtypes in zebrafish Tg(nr4a2a:eGFP) transgenics.
Goodings L, He J, Wood AJ, Harris WA, Currie PD, Jusuf PR
The study identifies that the NR4A2 gene is active in specific retinal amacrine cells during zebrafish development, including both dopamine-producing and other GABA-producing amacrine cells. This gene is expressed in a defined lineage of retinal cells and marks early stages of amacrine cell differentiation, making it a useful tool for studying how these cells form and function.
- NR4A2 is active in key retinal amacrine cells during development
- It labels both dopamine and GABA-producing amacrine cells
- Expression occurs in a specific cell lineage involving Atoh7 and Ptf1a
- The model helps track amacrine cell development in real time
- This tool can test how gene changes affect retinal cell formation
In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns.
Kim T, Song JJ, Puspita L, Valiulahi P, Shim JW, Lee SH
Researchers found that carefully controlling the levels and timing of two key genes, Nurr1 and Foxa2, in stem cells leads to the creation of fully mature midbrain dopamine neurons, which are the type lost in Parkinson's disease. This approach produces more stable and functional neurons than simply overexpressing the genes.
- Matching natural gene levels and timing is crucial for mature dopamine neurons
- Correct gene control prevents immature or unstable cells
- This method creates neurons suitable for therapy and research
- Improves long-term survival and function after transplantation
Regulation of human GDNF gene expression in nigral dopaminergic neurons using a new doxycycline-regulated NTS-polyplex nanoparticle system.
Espadas-Alvarez AJ, Bannon MJ, Orozco-Barrios CE, Escobedo-Sanchez L, Ayala-Davila J, Reyes-Corona D, Soto-Rodriguez G, Escamilla-Rivera V, De Vizcaya-Ruiz A, Eugenia Gutierrez-Castillo M, Padilla-Viveros A, Martinez-Fong D
This study developed a nanoparticle system that allows precise control of GDNF gene expression in dopamine-producing brain cells using doxycycline. The system can turn GDNF production on and off, reducing the risk of harmful side effects from long-term overexpression.
- GDNF expression can be turned on and off with doxycycline
- The system targets dopamine neurons safely and specifically
- Prevents harmful overexpression of GDNF
- Uses a nanoparticle delivery method for brain therapy
- Could improve Parkinson’s disease treatments
Identification of NURR1 (Exon 4) and FOXA1 (Exon 3) Haplotypes Associated with mRNA Expression Levels in Peripheral Blood Lymphocytes of Parkinson's Patients in Small Indian Population.
Tippabathani J, Nellore J, Radhakrishnan V, Banik S, Kapoor S
NURR1 and FOXA1 gene expression is significantly lower in blood cells of Parkinson's patients in this small Indian study, with greater reductions in males. Specific genetic variations in these genes may influence their activity and could help identify early signs of Parkinson's, especially when considering gender differences.
- NURR1 and FOXA1 levels are reduced in Parkinson's patients' blood cells
- Greater gene expression drop seen in male patients
- Genetic variations in NURR1 and FOXA1 may affect disease markers
- Findings suggest potential blood-based early detection tools
- Gender differences highlight need for tailored research
NR4A Receptors Differentially Regulate NF-κB Signaling in Myeloid Cells.
McEvoy C, de Gaetano M, Giffney HE, Bahar B, Cummins EP, Brennan EP, Barry M, Belton O, Godson CG, Murphy EP, Crean D
NR4A2 and NR4A3 boost the production of a key inflammatory signal (MIP-3α) while suppressing another (MCP-1) in immune cells, acting through the NF-κB pathway. This dual role suggests NR4A2 can both promote and limit inflammation at the same time, depending on the target gene.
- NR4A2 increases MIP-3α, a major inflammatory signal
- NR4A2 reduces MCP-1, another inflammatory molecule
- NR4A2 works through NF-κB without needing to bind DNA
- NR4A2 regulates RelB, a new target linked to inflammation
- Same receptor can both enhance and suppress inflammation
The NR4A subfamily of nuclear receptors: potential new therapeutic targets for the treatment of inflammatory diseases.
Rodríguez-Calvo R, Tajes M, Vázquez-Carrera M
NR4A2 (Nurr1) is part of a group of nuclear receptors that help control inflammation by turning off inflammatory signals. These receptors are activated during inflammation and may help shut it down to prevent long-term damage, making them potential targets for treating chronic inflammatory conditions.
- NR4A2 helps turn off inflammation to restore balance
- It is activated quickly during inflammatory responses
- NR4A2 may act as a natural brake on inflammation
- Targeting NR4A2 could lead to new anti-inflammatory treatments
- Few genes and mechanisms linked to NR4A2 are known yet
Cellular Model of Alzheimer's Disease: Aβ1-42 Peptide Induces Amyloid Deposition and a Decrease in Topo Isomerase IIβ and Nurr1 Expression.
Terzioglu-Usak S, Negis Y, Karabulut DS, Zaim M, Isik S
Aβ1-42, a toxic form of amyloid protein linked to Alzheimer's disease, reduces levels of two important brain proteins—topo IIβ and Nurr1—in lab-grown neurons. Lower topo IIβ directly causes reduced Nurr1, a protein critical for brain development and function, suggesting a potential pathway in neurodegeneration. This connection may inform future treatments targeting these proteins.
- Aβ1-42 reduces topo IIβ and Nurr1 in brain cells
- Low topo IIβ leads to lower Nurr1 levels
- Nurr1 is vital for brain development and function
- This pathway may contribute to neurodegeneration
- Could guide future therapies for NR4A2-related conditions
Transcriptional Regulation of DJ-1.
Takahashi-Niki K, Niki T, Iguchi-Ariga SMM, Ariga H
DJ-1 regulates key transcription factors involved in oxidative stress, dopamine production, and cell survival, with implications for Parkinson’s disease and metabolic function. Its role in modulating Nrf2, p53, and Nurr1 is particularly relevant to neuroprotection and brain health.
- DJ-1 controls Nrf2, p53, and Nurr1—critical for brain protection and dopamine synthesis
- Oxidative stress response is altered when DJ-1 function is impaired
- DJ-1 moves into the nucleus during cell growth, suggesting a role in development and repair
- Dysregulation of DJ-1 may contribute to Parkinson’s and metabolic issues
- Targeting DJ-1 pathways could offer new treatment strategies
Daphnane and Phorbol Diterpenes, Anti-neuroinflammatory Compounds with Nurr1 Activation from the Roots and Stems of Daphne genkwa.
Han BS, Minh NV, Choi HY, Byun JS, Kim WG
Daphne genkwa contains diterpenes that activate Nurr1 and strongly reduce brain inflammation, which may explain its potential benefits in Parkinson's disease and could inform future treatments for NR4A2-related conditions.
- Diterpenes from Daphne genkwa activate Nurr1
- They reduce brain inflammation more effectively than minocycline
- These compounds may support neuroprotection in NR4A2-related disorders
- Results come from cell and animal models of Parkinson's disease
Effects of Feeder Cells on Dopaminergic Differentiation of Human Embryonic Stem Cells.
Zhao Z, Ma Y, Chen Z, Liu Q, Li Q, Kong D, Yuan K, Hu L, Wang T, Chen X, Peng Y, Jiang W, Yu Y, Liu X
Human foreskin fibroblasts (HFFs) help human stem cells become dopamine-producing neurons more effectively than mouse fibroblasts, leading to neurons that are more mature and electrically active, which may inform future therapies for NR4A2-related disorders.
- HFFs boost dopamine neuron formation from stem cells
- Neurons from HFFs show higher levels of key genes like NURR1 and TH
- HFF-derived neurons are more electrically active and mature
- Feeder cells significantly influence neuron quality and function
- Findings may guide better stem cell-based treatments
Transcriptomic Analysis Shows Decreased Cortical Expression of NR4A1, NR4A2 and RXRB in Schizophrenia and Provides Evidence for Nuclear Receptor Dysregulation.
Corley SM, Tsai SY, Wilkins MR, Shannon Weickert C
People with schizophrenia have lower levels of NR4A2 and other related nuclear receptors in the brain's thinking center, which may contribute to the disorder. These changes could be influenced by antipsychotic medications and may disrupt the activity of many downstream genes.
- NR4A2 (Nurr1) is reduced in the brain of people with schizophrenia
- Other nuclear receptors like NR4A1 and RXRB are also lower
- Lower levels may be linked to antipsychotic drug exposure
- These receptors help control many other genes in the brain
- Changes may play a role in the brain differences seen in schizophrenia
MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats.
Singh S, Mishra A, Srivastava N, Shukla S
MK-801, an NMDA receptor blocker, boosts the birth and survival of new brain cells in the hippocampus of Parkinson’s disease model rats, reduces anxiety and depression-like behaviors, and protects dopamine-producing neurons by activating the Wnt/β-catenin pathway. This suggests a potential way to treat nonmotor symptoms in Parkinson’s that don’t respond to standard dopamine therapy.
- MK-801 enhances new brain cell formation in the hippocampus
- It reduces anxiety and depression-like behaviors in Parkinson’s rats
- It protects dopamine neurons and improves motor function
- It works by activating the Wnt/β-catenin brain repair pathway
- May offer a treatment strategy for nonmotor symptoms in Parkinson’s
Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.
Gracia-Rubio I, Martinez-Laorden E, Moscoso-Castro M, Milanés MV, Laorden ML, Valverde O
Early-life stress from maternal separation reduces the brain's response to cocaine in adolescent mice, likely due to changes in dopamine system proteins, including lower levels of a key brain protector called Nurr1. This suggests early stress may alter brain development in ways that affect substance use vulnerability.
- Maternal separation reduces cocaine's behavioral effects in mice
- Dopamine system changes include lower Nurr1 and D2 receptors
- Nurr1 is linked to NR4A2, a gene related to neurodevelopmental disorders
- These changes may affect long-term substance use risk
- Findings highlight dopamine system vulnerability from early stress
Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion.
Bux AS, Lindsey ML, Vasquez HG, Taegtmeyer H, Harmancey R
Glucose influences how the heart responds to surgical stress by shaping the activity of immune cells in the heart, particularly macrophages, which play a role in inflammation and tissue repair after injury. This effect is impaired in insulin-resistant conditions, suggesting metabolic health affects recovery.
- Glucose boosts inflammatory and repair-related gene activity in heart tissue after surgery
- NR4A2, a key gene linked to immune cell function, is strongly upregulated during heart stress
- Glucose helps drive macrophages toward a tissue-repairing state, but this fails in insulin resistance
- Heart stress from surgery triggers a gene response similar to what happens in patients
- Metabolic health may influence how well the heart heals after surgery
Nurr1 overexpression exerts neuroprotective and anti-inflammatory roles via down-regulating CCL2 expression in both in vivo and in vitro Parkinson's disease models.
Liu W, Gao Y, Chang N
Overexpressing the Nurr1 protein protects brain cells and reduces inflammation in Parkinson's disease models by lowering levels of a harmful molecule called CCL2. This effect happens in both lab tests and animal models, suggesting a potential treatment path for neurodegeneration.
- Nurr1 protects brain cells in Parkinson's models
- Nurr1 reduces harmful inflammation by lowering CCL2
- Lowering CCL2 improves cell survival and function
- Nurr1 overexpression improves movement and memory in mice
- Targeting Nurr1 or CCL2 could lead to new therapies
Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala.
Kwapis JL, Alaghband Y, López AJ, White AO, Campbell RR, Dang RT, Rhee D, Tran AV, Carl AE, Matheos DP, Wood MA
HDAC3 enzyme activity in the amygdala suppresses fear memory formation, with distinct roles in different subregions: blocking HDAC3 in the basal amygdala strengthens context fear, while blocking it in the lateral amygdala enhances tone fear. This suggests that targeting HDAC3 could help fine-tune specific fear responses.
- HDAC3 activity suppresses fear memory formation
- Blocking HDAC3 boosts context fear in the basal amygdala
- Blocking HDAC3 boosts tone fear in the lateral amygdala
- HDAC3 regulates different fear types in different brain areas
- Targeting HDAC3 may help treat specific fear-related symptoms
Mapping of a FEB3 homologous febrile seizure locus on mouse chromosome 2 containing candidate genes Scn1a and Scn3a.
Hessel EV, van Lith HA, Wolterink-Donselaar IG, de Wit M, Groot Koerkamp MJ, Holstege FC, Kas MJ, Fernandes C, de Graan PN
This study identified two genetic regions on mouse chromosome 2 linked to febrile seizure susceptibility, one of which matches a known human febrile seizure gene location. Genes in this region, including Scn1a and Scn3a, are involved in brain electrical activity and may contribute to seizure risk. The findings support the use of mouse models to study human febrile seizures.
- Mouse model identifies febrile seizure genes on chromosome 2
- Scn1a and Scn3a are strong candidates for seizure susceptibility
- One region matches a human febrile seizure gene location
- Differences in gene expression between mouse strains suggest biological relevance
In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats.
Fedeli D, Montani M, Bordoni L, Galeazzi R, Nasuti C, Correia-Sá L, Domingues VF, Jayant M, Brahmachari V, Massaccesi L, Laudadio E, Gabbianelli R
Early exposure to permethrin in rats disrupts dopamine-related brain pathways, increasing proteins linked to Parkinson's disease and altering enzymes that control gene activity, even at low doses. These changes persist into adulthood and are linked to the pesticide's buildup in the brain and its direct interaction with the Nurr1 protein.
- Permethrin accumulates in the brain after early exposure
- Increases in alpha-synuclein and DNMTs suggest Parkinson's-like changes
- Permethrin binds directly to Nurr1, disrupting dopamine regulation
- Changes vary with age, showing long-term neurotoxic effects
- No change in Nurr1 gene methylation, but protein function is affected