The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction

Kermath, Bailey A.; Vanderplow, Amanda M.; Bjornson, Kathryn; Seablom, Erin N.; Novak, Annie; Bernhardt, Cassandra; Cahill, Michael E.

doi:10.1038/s41380-020-0835-0

Cited by 12 publications

(54 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, we evaluated the possibility that the increase in layer 2/3 total spine density in 8-week-old GIH offspring was due to an increase in the density of a particular spine morphological subtype. On the basis of spine head morphology, spines were semiautomatically classified into 3 subtypes—thin, stubby, or mushroom—using our established methods [ 73 – 75 ]. Spines lacking a discernable neck were classified as stubby.…”

Section: Resultsmentioning

confidence: 99%

“…Z-stack images were collapsed and deconvolved via a full-focus algorithm. NeuronStudio semiautomatic neuron analysis program was used for dendritic spine quantification using our established procedures [ 73 – 75 ]. A hollow ellipse is automatically placed on each individual spine head, such the diameter of the ellipse corresponds to the diameter of the spine head.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

et al. 2022

Self Cite

View full text Add to dashboard Cite

Mounting epidemiologic and scientific evidence indicates that many psychiatric disorders originate from a complex interplay between genetics and early life experiences, particularly in the womb. Despite decades of research, our understanding of the precise prenatal and perinatal experiences that increase susceptibility to neurodevelopmental disorders remains incomplete. Sleep apnea (SA) is increasingly common during pregnancy and is characterized by recurrent partial or complete cessations in breathing during sleep. SA causes pathological drops in blood oxygen levels (intermittent hypoxia, IH), often hundreds of times each night. Although SA is known to cause adverse pregnancy and neonatal outcomes, the long-term consequences of maternal SA during pregnancy on brain-based behavioral outcomes and associated neuronal functioning in the offspring remain unknown. We developed a rat model of maternal SA during pregnancy by exposing dams to IH, a hallmark feature of SA, during gestational days 10 to 21 and investigated the consequences on the offspring’s forebrain synaptic structure, synaptic function, and behavioral phenotypes across multiples stages of development. Our findings represent a rare example of prenatal factors causing sexually dimorphic behavioral phenotypes associated with excessive (rather than reduced) synapse numbers and implicate hyperactivity of the mammalian target of rapamycin (mTOR) pathway in contributing to the behavioral aberrations. These findings have implications for neuropsychiatric disorders typified by superfluous synapse maintenance that are believed to result, at least in part, from largely unknown insults to the maternal environment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, the active form of Rap1, but not its gene and protein expression levels, was decreased after RF-EMR exposure. Altered Rap1-GTP levels were found in the prefrontal cortex of depressed individuals who had committed suicide and in the frontal cortex of patients with schizophrenia and severe depressive disorders ( 48 ). Transfection of a constitutively active Rap1 (F64A) plasmid reversed the inhibitory effect of Myelin-associated glycoprotein (MAG) on the neurite growth of dorsal root ganglion (DRG) neurons, possibly by decreasing the expression of Rap1-GTP, limiting neurite outgrowth ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

1,800 MHz Radiofrequency Electromagnetic Irradiation Impairs Neurite Outgrowth With a Decrease in Rap1-GTP in Primary Mouse Hippocampal Neurons and Neuro2a Cells

Deng

Chen

et al. 2021

Front. Public Health

View full text Add to dashboard Cite

Background: With the global popularity of communication devices such as mobile phones, there are increasing concerns regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on the brain, one of the most important organs sensitive to RF-EMR exposure at 1,800 MHz. However, the effects of RF-EMR exposure on neuronal cells are unclear. Neurite outgrowth plays a critical role in brain development, therefore, determining the effects of 1,800 MHz RF-EMR exposure on neurite outgrowth is important for exploring its effects on brain development.Objectives: We aimed to investigate the effects of 1,800 MHz RF-EMR exposure for 48 h on neurite outgrowth in neuronal cells and to explore the associated role of the Rap1 signaling pathway.Material and Methods: Primary hippocampal neurons from C57BL/6 mice and Neuro2a cells were exposed to 1,800 MHz RF-EMR at a specific absorption rate (SAR) value of 4 W/kg for 48 h. CCK-8 assays were used to determine the cell viability after 24, 48, and 72 h of irradiation. Neurite outgrowth of primary hippocampal neurons (DIV 2) and Neuro2a cells was observed with a 20 × optical microscope and recognized by ImageJ software. Rap1a and Rap1b gene expressions were detected by real-time quantitative PCR. Rap1, Rap1a, Rap1b, Rap1GAP, and p-MEK1/2 protein expressions were detected by western blot. Rap1-GTP expression was detected by immunoprecipitation. The role of Rap1-GTP was assessed by transfecting a constitutively active mutant plasmid (Rap1-Gly_Val-GFP) into Neuro2a cells.Results: Exposure to 1,800 MHz RF-EMR for 24, 48, and 72 h at 4 W/kg did not influence cell viability. The neurite length, primary and secondary neurite numbers, and branch points of primary mouse hippocampal neurons were significantly impaired by 48-h RF-EMR exposure. The neurite-bearing cell percentage and neurite length of Neuro2a cells were also inhibited by 48-h RF-EMR exposure. Rap1 activity was inhibited by 48-h RF-EMR with no detectable alteration in either gene or protein expression of Rap1. The protein expression of Rap1GAP increased after 48-h RF-EMR exposure, while the expression of p-MEK1/2 protein decreased. Overexpression of constitutively active Rap1 reversed the decrease in Rap1-GTP and the neurite outgrowth impairment in Neuro2a cells induced by 1,800 MHz RF-EMR exposure for 48 h.Conclusion: Rap1 activity and related signaling pathways are involved in the disturbance of neurite outgrowth induced by 48-h 1,800 MHz RF-EMR exposure. The effects of RF-EMR exposure on neuronal development in infants and children deserve greater focus.

show abstract

“…The Y-maze was purchased from Maze Engineers (Skokie, IL, USA), with each arm 11-cm wide and 50-cm long. Y-maze methods were adopted from our established methods [54,73]. For each test, criteria for arm entry included an animal having its hind paws completely within a maze arm.…”

Section: Methods Detailsmentioning

confidence: 99%

“…Next, we evaluated the possibility that the increase in layer 2/3 total spine density in 8-week-old GIH offspring was due to an increase in the density of a particular spine morphological subtype. On the basis of spine head morphology, spines were semiautomatically classified into 3 subtypes-thin, stubby, or mushroom-using our established methods [73][74][75]. Spines lacking a discernable neck were classified as stubby.…”

Section: Dendritic Spine Density and Morphology Is Altered In Gih Off...mentioning

confidence: 99%

Untitled

View full text Add to dashboard Cite

The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction

Cited by 12 publications

References 86 publications

A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

1,800 MHz Radiofrequency Electromagnetic Irradiation Impairs Neurite Outgrowth With a Decrease in Rap1-GTP in Primary Mouse Hippocampal Neurons and Neuro2a Cells

Untitled

Contact Info

Product

Resources

About