L5 MIA & Offspring Neurodevelopment Flashcards
Pregnancy involves complex changes to the maternal immune system that can be categorised into 3 stages:
- Implantation
- The duration of pregnancy
- Late pregnancy and labour
The first few weeks of pregnancy are characterised by…
an increased pro-inflammatory response
On day 6, the blastocyst attaches to the endometrium. The endometrium transforms into the __ , which is then infiltrated by __
decidua
maternal innate immune cells
Syncytiotrophoblast expresses no __
HLA
What is placenta-decidua crosstalk via immune molecules, such as cytokines, crucial for?
implantation, uterine remodelling and placentation
For the longest part of gestation (late 1st to early 3rd trimester), the immune response is generally __
anti-inflammatory
A heightened immune response for the duration of pregnancy is associated with…
placental disorders and miscarriage
Changes to cells of the immune system for the duration of pregnancy
- increased activity of complement system & monocytes
- reduction in T & B cells
What type of immune response is seen towards the end of a healthy pregnancy?
pro-inflammatory (important for labour & childbirth)
Which cytokine in particular is crucial for initiating childbirth?
IL-6
Schizophrenia risk factors
- seasonality effect: Spring baby
- birth in a city
- maternal 2nd trimester Influenza infection
- genetics
The most common vertically transmitted pathogens
TORCH pathogens: Toxoplasma gondii, other (HepB, HepE, HIV, Zika, syphilis), rubella, CMV, HSV
2 examples of vertically transmitted viruses that can directly affect fetal neurodevelopment
HSV and Zika (high degree of neurotropism)
Maternal infection increases the risk of…
Schizophrenia and ASD development
What is the term given to stimulation of a pro-inflammatory state by the mother’s immune system during pregnancy?
Maternal immune activation (MIA)
When does MIA occur?
in response to infection and other stimuli, and certain maternal or gestational disorders
4 ways to induce MIA in animals
Poly I:C (dsRNA)
LPS
Enterotoxins
Transgenic animals with human receptors
What causes Influenza-induced behavioural deficits in mice?
viral-induced MIA, rather than the virus itself
Early prenatal LPS exposure in rats alters __ , whereas late exposure causes __
reward-seeking behaviour
motor deficits
Prenatal Poly I:C exposure in mice causes…
DA and 5-HT imbalances, mimicking the neurochemical alterations of schizophrenia
How does MIA affect microglial activity?
It increases microglial activity, thereby affecting cortical cytoarchitecture and neural activity in brains of exposed offspring
What is the Cytokine Hypothesis of neurodevelopmental disorders?
The increased risk for neurodevelopmental disorders caused by maternal infection is due not to the specific pathogen itself, but the MIA it induces, and as a result, high levels of cytokines reaching the fetal brain.
Neuroinflammation can be seen in patients with…
ASD and schizophrenia
Roles of IL-6 in the brain
- promotes neuronal differentiation, growth & survival
- induces death in 5-HT neurons
- activates microglia
