Lecture 7 Part III Flashcards
(40 cards)
how is GR expression regulated
-GR expression is up-regulated because licking/ grooming activates transcription factors/coactivators involved in turning on GR gene expression.
-Pup licking/grooming from the mother increases NGFI-A expression and binding to the promoter of the GR gene
specifically exon 17
-The increased binding of NGFI-A to the promoter is limited exclusively to the licking/ grooming bout.
regulation of the GR gene
-GR gene has a regulatory region and a coding region
- exon 1 of the GR gene includes a number of promoter sequences (1,2,3,4,5,6,7, etc) these are axons that end up in the mRNA sequence
- Also are locations in which transcription factors bind
- Exon 1-7 happens to have a pretty good amount of homology with the region in the human GR gene we called exon 1F
- This is the site that we think is driving the differences in GR gene expression through that NGF1-A transcription factor
GR regulation pathway
Moms licking —> serotonin is released —> binds to serotonin receptor —> activation of the signaling cascade —> activates NGFI-A transcription factors —> binds neuron specific location where we only see activation within neurons —> binds to exon 17 of the GR promoter —> start to get GR transcript
how does GR expression persist in adulthood ?
-The same pattern of expression is seen in adulthood
–Is like licking and grooming turns on this knob and from now on pup is going to make more GR receptors and that pattern will continue to adulthood
how is the maternal effect renders stable?
- The difference in pup licking between high and low mothers is apparent in the first week of light, but these offspring continue to show altered behavioral and physiological stress responses in adulthood (long after the initial tactile stimulation).
- GR mechanism hasn’t been investigated to the same extent in females
- If female is raised in a low LG environment she will also spend little time LG her offspring
- This model is what allows us to do cross-fostering necessary to show that is not about some genetic lineage, but environment
like mother, like daughter
- Female offspring that are reared by high licking/ grooming mothers become high licking/grooming mothers when they are adults.
- If moms spends a lot of time LG then her offspring will also spend a lot of time LG their offspring
- Environment is transmitted in a way through this variation in social behavior
- The most important region for maternal behavior is MPOA
the transmission of this phenotype is related to methylation of the estrogen receptor alpha gene.
what is the evidence for this
- Looking at female offspring investigators have found that estrogen receptor alpha is regulated in such a way that there is a development pattern of estrogen receptor alpha expression in the MPOA that varies based on that early life environment
- High LG by mom = high levels of estrogen receptor alpha levels in the MPOA
- Low LG by mom = low levels of estrogen receptor alpha levels in the MPOA
Why is there higher levels of estrogen receptor alpha levels in the MPOA in female offspring raised by high LG moms?
- Higher levels of estrogen receptor alpha probably stimulate higher levels of maternal behavior in the MPOA
- This difference in expression is likely related to the behavioral phenotype that we see b/c estradiol acts on the MPOA to initiate maternal behavior by driving oxytocin receptor expression
limited bedding model method
○ Induces a very aversive state
○ Limit the amount of bedding the mother rat has which prevents her from performing her maternal tasks
-Take away the rats resources
limited bedding model is used primarily to study what
to study offspring development as a result of this early life adversity
limited bedding results
-Due to the discomfort mother gets very frustrated b/c she cant build a nest properly so she displays neglect and even maltreatment/abusive behavior
- These pups as they get older and develop into adulthood they display
- High anxiety phenotypes
- Poor cognitive control
- Depressive like phenotypes
-Females when they grow up and interact with their offspring are not very good moms
T or F: Something about our adult mothering behavior is from when we ourselves are infants
true
when looking at maternal behavior in females that experience maltreatment when they were offspring the researchers found that
-when they have their offspring and are given all of the bedding they could need they still display behaviors that are very similar to the kinds of behaviors that their mom displayed towards them in the adverse environment
- They step on their pups
- Show a significant reduction in nursing posture
- Rough handle the pups
- Abusing the pups
looking at BDNF in offspring that experience early adversity the results showed that
- In the prefrontal cortex is affected by these early life aversive experiences
- BDNF methylation in prefrontal cortex being altered as a result of these early life adversity
These alterations in BDNF have been linked to a risk for depression and anxiety
- There is an increase in methylation of BDNF in this particular exon and that increased in BDNF is present and seen in adulthood
- The increase is relative offspring that didn’t experience any adversity
- The more methylation of BDNF the less expression of BDNF which plays a role in terms of cognition in prefrontal cortex
harlow’s work
an early demonstration of how tactile stimulation was important for early life experience
Alison Fleming’s work
- wanted to understand how early life really extreme deprivation impacts development
- In the artificial reared condition she has a feeding tube, are completely separated from their moms, and are thermally regulated by an incubator and they received LG from a paintbrush
- Offspring that experienced this artificial rearing procedure showed similar problems as the offspring being reared by bad moms and were bad mothers themselves
- offspring are less attentive, more impulsive and poor mothers
socioeconomic status affects what
prenatal factors, parental care, cognitive stimulation —> brain development —-> cognition, academic achievement, mental health
SES is associated with adverse adult outcomes
- Increased depression
- Increased anxiety
- Attention problems
- Conduct disorders
- Aggressive or impulsive behavior
- Decreased academic achievement
animal model correlate for poor nutrition
Underfeeding/Overfeeding
development
animal model correlate for poor parental care
Maternal neglect; exposure to different mothering styles
animal model correlate for neighborhood and family
Communal nesting? “Single moms”
animal model correlate for exposure to violence
Maternal abuse, Social abuse
animal model correlate for material resources and reduced cognitive stimulation
Enrichment versus deprived environment
animal model correlate for exposure to toxins
Endocrine-disrupting compound exposure in utero or during postnatal
