Early life stress in fathers impairs synaptic plasticity in the offspring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47848 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA208074
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-01 | E-GEOD-47848 | biostudies-arrayexpress
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress. Male mice were exposed to chronic traumatic stress in early postnatal life and were later bred to naM-CM-/ve females to produce second-generation offspring. Memory performance was evaluated in the offspring, and synaptic plasticity was examined in the hippocampus and the amygdala, brain areas important for memory formation. The two groups tested were 1: offspring of fathers which were stressed (MSUS - maternal separation unpredictable stress) and 2: offspring of non-stressed fathers (control). Genome-wide gene expression in hippocampus of these two groups was assessed at rest (this study) and after acute stress.
2014-07-01 | E-GEOD-47846 | biostudies-arrayexpress
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress. Male mice were exposed to chronic traumatic stress in early postnatal life and were later bred to naM-CM-/ve females to produce second-generation offspring. Memory performance was evaluated in the offspring, and synaptic plasticity was examined in the hippocampus and the amygdala, brain areas important for memory formation. The two groups tested were 1: offspring of fathers which were stressed (MSUS - maternal separation unpredictable stress) and 2: offspring of non-stressed fathers (control). Genome-wide gene expression in hippocampus of these two groups was assessed at rest and after acute stress (this study).
2014-07-01 | E-GEOD-47847 | biostudies-arrayexpress
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress.
2014-07-01 | GSE47846 | GEO
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress.
2014-07-01 | GSE47847 | GEO
Project description:Early life adversity impairs normal hippocampal function and connectivity in various mammalian species, including humans and rodents. According to the 'cumulative model' the number of early adversities can be summed up to determine the risk for developing psychopathology later in life. In contrast, the 'dimensional model' argues that 'Deprivation' and 'Threat' impact different developmental processes that should not be added in determining clinical outcomes. Here we examine these predictions in male and female mice exposed to a single adversity - limited bedding (LB) - versus mice exposed to multiple adversities - unpredictable postnatal stress (UPS) - focusing on microglia-mediated synaptic pruning in the developing hippocampus. Exposure to both LB and UPS reduced the ramification of microglia, impaired their ability to phagocytose synaptic material in vivo and ex vivo, and decreased expression of TREM2. Abnormal phagocytic activity was associated with increased spine density in CA1 pyramidal neurons that was seen in 17-day-old groups and persisted in peri-pubescent 29-day-old LB and UPS mice. Exposure to LB caused more severe impairment in microglial ramification and synaptic engulfment compared to UPS, outcomes that were accompanied by a UPS-specific increase in the expression of several genes implicated in synaptic pruning. We propose that despite being a single stressor, LB represents a more severe form of early deprivation, and that appropriate levels of hippocampal stimulation during the second and third weeks of life are necessary to support normal microglial ramification and synaptic pruning. Further, impaired synaptic pruning during this critical period of hippocampal development contributes to the abnormal hippocampal function and connectivity seen in UPS and LB later in life.
| S-EPMC10497209 | biostudies-literature
Project description:Early-life stress (ELS) predisposes individuals to psychiatric disorders, including anxiety and depression, and cognitive impairments later in life. However, the underlying molecular mechanisms are not completely understood. Developmental deficits in hippocampal synaptic plasticity are among the primary detrimental alterations in brain function induced by ELS. Impaired synaptic plasticity is usually accompanied by decreased synaptic proteins, such as postsynaptic density 95 (PSD95) and synaptophysin, which are important for synaptic function. The mTOR signaling pathway plays a vital role in regulating protein translation, and mTOR activation is functionally associated with synaptic protein synthesis. In the present study, we observed whether ELS impacts synaptic protein synthesis and mTOR signaling, which is involved in synaptic plasticity. Herein, we established a maternal separation (MS) and chronic restraint stress (CRS) model and evaluated anxiety-like behavior and cognitive function (e.g., learning and memory) in adulthood through behavioral examination and analyzed hippocampal expression levels of PSD95 and synaptophysin. To explore whether the mTOR signaling pathway was associated with ELS, we also examined the activity of mTOR and s6. The behavior tests indicated that maternally separated mice showed increased anxiety-like behavior and cognitive impairments. PSD95 and synaptophysin mRNA and protein expression levels were decreased in the hippocampus, and phosphorylated mTOR and phosphorylated s6 were significantly decreased in maternally separated mice vs. those not exposed to MS. Our data demonstrate that MS impairs synaptic plasticity and inhibits mTOR signaling, specifically via s6. Therefore, we speculate that ELS decreased synaptic plasticity via the inhibition of the mTOR pathway in the hippocampus, which may underlie vulnerability to stress and mental disorders in adulthood.
| S-EPMC7767996 | biostudies-literature
Project description:A high salt (HS) diet is detrimental to cognitive function, in addition to having a role in cardiovascular disorders. However, the method by which an HS diet impairs cognitive functions such as learning and memory remains open. In this study, we found that mice on a 7 week HS diet demonstrated disturbed short-term memory in an object-place recognition task, and both 4 week and 7 week HS treatments impaired long-term memory, as evidenced in a fear conditioning test. Mechanistically, the HS diet inhibited memory-related long-term potentiation (LTP) in the hippocampus, while also increasing the levels of reactive oxygen species (ROS) in hippocampal cells and downregulating the expression of synapsin I, synaptophysin, and brain-derived neurotrophic factor in specific encephalic region. This suggests that oxidative stress or synaptic protein/neurotrophin deregulation was involved in the HS diet-induced memory impairment. Thus, the present study provides novel insights into the mechanisms of memory impairment caused by excessive dietary salt, and underlined the importance of controlling to salt absorb quantity.
| S-EPMC5656827 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-01-20 | E-GEOD-33564 | biostudies-arrayexpress
Project description:Febrile seizures (FSs) in early life are significant risk factors of neurological disorders and cognitive impairment in later life. However, existing data about the impact of FSs on the developing brain are conflicting. We aimed to investigate morphological and functional changes in the hippocampus of young rats exposed to hyperthermia-induced seizures at postnatal day 10. We found that FSs led to a slight morphological disturbance. The cell numbers decreased by 10% in the CA1 and hilus but did not reduce in the CA3 or dentate gyrus areas. In contrast, functional impairments were robust. Long-term potentiation (LTP) in CA3-CA1 synapses was strongly reduced, which we attribute to the insufficient activity of N-methyl-D-aspartate receptors (NMDARs). Using whole-cell recordings, we found higher desensitization of NMDAR currents in the FS group. Since the desensitization of NMDARs depends on subunit composition, we analyzed NMDAR current decays and gene expression of subunits, which revealed no differences between control and FS rats. We suggest that an increased desensitization is due to insufficient activation of the glycine site of NMDARs, as the application of D-serine, the glycine site agonist, allows the restoration of LTP to a control value. Our results reveal a new molecular mechanism of FS impact on the developing brain.
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