Lecture 11; Brain development Lecture 3 Flashcards

Question

What are subcortical Band Heterotopia ?

Answer 1

Bands of neurons are located in the white matter between the cortex and the lateral ventricles

Answer 2

•Majority of cases due to mutations of the doublecortin (DCX) gene –Encodes the DCX protein expressed in migrating neuroblasts –Regulates cytoskeletal dynamics and neuroblast migration DCX is important in growth cones and radial glial movement

Answer 3

Spectrum of abnormalities of the laminar structure of the cortex

Answer 4

•Various cytopathological features –Giant neurons –Dysmorphic neurons –Balloon cells (enlarged cell bodies but no dendrites/axons)

Answer 5

•Abnormal migration, maturation, and cell death –Causes unknown

Answer 6

•Intractable epilepsy in children•Developmental delays

Answer 7

•Group of disorders characterized by progressive white matter degeneration

Answer 8

•Mutations in genes that produce or maintain myelin–Oligodendrocyte death and myelin degeneration

Answer 9

•Manifest during childhood (incurable, premature death) –Symptoms vary according to the specific type of leukodystrophy –Progressive decline in motor, cognition, and language skills –MRI pathology typically hypomyelination

Answer 10

•Metachromatic leukodystrophy, Krabbé disease, Adrenoleukodystrophy, Pelizaeus-Merzbacher disease, Canavan disease, Childhood Ataxia with CNS Hypomyelination (Vanishing White Matter Disease)

Answer 11

Pathology: Oligodendrocyte cell death, diffuse disappearance of white matter, loss of myelin

Answer 12

Mutations in eIH2B1-5 genes (oligodendrocyte survival/apoptosis)

Answer 13

* Childhood ataxia (gait difficulties) | * Rapid cognitive decline (2-5 years)

Answer 14

•Metabolic disorder (1:10,000)–Mutation in phenylalanine hydroxylase

Answer 15

•Baby cannot digest the dietary amino acid phenylalanine (e.g. in milk) •Phenylalanine accumulates in brain –Inhibits HMG-COA reductase to decrease cholesterol synthesis –Oligodendrocytes do not produce myelin hypomyelonation

Answer 16

* Impaired brain development and intellectual disability | * Strict diet with no phenylalanine

Answer 17

•Some infectious diseases can be transmitted congenitally or in early childhood, and can cause serious neurodevelopmental disorders including schizophrenia

Answer 18

•Congenital toxoplasmosis (protozoa Toxoplasma gondii) – domestic cat –Can cause cyst formation in the brain; seizures; intellectual disability –Most damaging in first trimester

Answer 19

•Congenital syphilis can progress to neurosyphilis and brain defects –Most damaging in third trimester

Answer 20

•Measles can progress to subacute sclerosing panencephalitis –Causes oligodendrocyte and neuronal cell death –Mental deterioration and death within 3 years

Answer 21

•Congenital rubella syndrome linked to schizophrenia –Also, hearing impairment and visual impairment –First few weeks of gestation is a critical period for negative effects

Answer 22

Immune reactions during pregnancy and in infant can produce neurodevelopmental disorders –Sydenham’s Chorea –Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) Both are autoimmune reactions against brain tissue following Group A Streptococcus bacteria infection

Answer 23

•Kills neurons in the corpus striatum of the basal ganglia

Answer 24

•Abnormal movements of the body, emotional disturbances, altered cognition, tics, and obsessive compulsive disorder symptoms

Answer 25

•Chorioamnionitis (maternal infection) –Inflammation of fetal membranes due to bacterial infection –Bacteria ascending into the uterus–Typically non-pathogenic (e.g., staph aureus

Answer 26

–Associated with high rates of motor (e.g. cerebral palsy) and neurocognitive deficits –Fetal/newborn inflammation (inflammatory response syndrome) •Neonatal sepsis (bacterial infection spread via blood stream)

Answer 27

•Chorioamnionitis associated with elevated levels of inflammatory molecules in fetus/neonate

Answer 28

* CNS inflammation following systemic infection | * FIRS important cause of in utero/postnatalbrain injury

Answer 29

•Fetal metabolism altered by: –Maternal nutrition (e.g., folate deficiency) –Maternal neurotoxins/teratogens (nicotine, alcohol etc.) exposure, diabetes = NDD

Answer 30

–In-born errors of metabolism (IEM) – single gene defects in biochemical pathways (Phenylketonuria) –Lysosomal storage disorders (intracellular structures responsible for break down of metabolic waste products) =NDD

Answer 31

In children, diabetes can produce impaired neurodevelopment/cognition

Answer 32

In utero, a non-diabetic fetus can also be subjected to glucose effects if its mother has undetected gestational diabetes (~6% of all pregnancies) –~10-fold increase in congenital abnormalities if during 1st trimester –CNS defects including anencephaly and spina bifida –Seizures –Delays in motor and cognitive function in childhood

Answer 33

hildren who were affected in the second trimester of their mother's pregnancy had 10X increased incidence of Schizophrenia as adults At 56-59 years of age, showed impaired cognitive ability due to accelerated brain aging

Answer 34

Exogenous agents that causes birth defects

Answer 35

Each organ system is most vulnerable to disruption at the time when it is developing most rapidly

Answer 36

Accutane (13-cis-retinoic acid) produced as treatment for acne –>2,000 women using this during pregnancy had high rates of children born with birth defects –Hearing and visual impairment, intellectual disability

Answer 37

•2% of women drink significantly during pregnancy (binge), 10% drink some

Answer 38

Fetal brain damage occurs at regular doses of 1-2 oz/da

Answer 39

* Infant: Problems with sleep, feeding, milestones, muscle tone, sensory information processing * Child: Hyperactive, poorly coordinated, learning delays * Adolescent/Adult: poor judgment, attention, problems with arithmetic, memory, abstraction, frustration/anger

Answer 40

Alcohol inhibits all stages of brain development, except neuronal death, which it promotes

Answer 41

•Nicotine is a fetal neuroteratogen –Targets nicotinic acetylcholine receptors in the fetal brain –Impairs cell proliferation and differentiation, synaptogenesis, and induced neuronal apoptosis –Constricts placental blood vessels, to reduced blood flow/nutrients to fetus

Answer 42

Decreased IQ, depression, criminal behavior

Answer 43

Spectrum of nervous system damage including neurodevelopmental behavioral disorders in children, visual impairment, impaired coordination, hallucinations, intellectual disability, depression, and death

Answer 44

* Neuronal, astrocyte, and oligodendrocyte apoptosis | * Altered neurotransmitter storage/release