Smoking and Brain Development

Effects of Smoking during Pregnancy: Apply to second hand smoke

  • reduced fetal growth

  • spontaneous abortion

  • preterm birth

  • SIDS

  • increased chance of death at birth

  • increased risk of behavior and emotional disorders

  • lower cognitive abilities

  • Motality rate is 71% higher for infants of smokers

Growth Effects:

  • increased risk of low birth weight

  • increased risk of microcephaly

  • abnormal artery flow

  • increased vascular resistance in fetal vessels

  • impaired oxygen exchange

  • chronic hypoxia

  • mititoc arrest→ cell death

Smoking, Mechanisms and Outcomes

Smoking and SIDS

  • exposure to second hand smoke leads to respiratory illnesses and SIDS

    • Ammonia , formaldehyde, cadmium, chromium, lead, isoprene, benze

  • associated with hypoplasia of the arcuate nucleus which has autonomic functions

    • kainate, muscarinic, cholinergic and serotonin receptor associations

  • Genetic risk factors of SIDS:

    • cardiac ion channelopathies

    • polymorphins

    • genetic alterations

Nicotine

  • along with CO causes vasoconstriction in the placenta and fetal tissues

  • high lipid solubility

  • main metabolite is cotine, and makes its way into embryonic and fetal bloodstresm

  • First metabolized in the lungs, mostly metabolized in the liver

    • cotine has a longer half life

  • A fetus might be exposed to higher concentrations of nicotine than a smokeing mother

  • Excreted: urine and breast milk

Nicotine and Acetylcholine

  • nicotine binds to acetylcholine receptors (nAChRs)

  • nAChRs are widely expressind in fetal CNS

  • Neuronal nicotinic ssystems are in cholinergic neurons

  • Non-neuronal nicotinic systems inclde cell proliferation, differentiation and migration

Heteromeric Acetylcholine Rs

  • gate Na+

  • have alpha and beta subunits

Homomeric Acetylcholine Rs

  • gate Ca2+ and Na+

  • only have alpha subunits

  • nicotinic receptors are necessary for cognitive development and have gene expression as early as 4-5 weeks (neural tube stage)

  • nAChRs activation interefered in DA, NE and Serotonin

  • play a role in neurite growth, synaptogenesis, gene expression, cell prolif. and diff. and apoptosis

Behavioral/ Psychiatric disorders associated with smoking during pregnancy

  • Conduct disorder

  • ADHD/ADD

  • Alcohol/substance abuse

  • depression

  • low IQ/ cognitive deficit

Effects on brain structures and brain development

  • thinning cortex

  • microcephaly/microencephaly

  • myelin death

  • promotes gliogenesis in the dentate gyrus and diminishes neurogenesis

    • associated with BDNF

  • impairs proliferation and maturation of neuronal progenitons,

  • fewer GLUT neurons in th medial prefrontal cortex

Mitochondria as a target for Nicotine

In vitro (isolated)

  • impact expression level of respiratory chain subunits

  • lower activity of individual complexes

  • lower O2 consumption

  • lower ROS

Activation of ROS and Ca2+ dependent signaling pathways

  • stimulation of biogenesis

  • increased mitochondria-ER contacts

  • transient mitochondrial fragmentation and dissosciation from microtubules

Both lead to a stress response which leads to either adaptation or cell death

In situ (intact cells)

  • impact the expression level of respiratory chain subunits

  • increased oxygen uptake/consumption

  • change levels of antioxidant enzymes

  • increased Ca2+

  • increased ROS

  • increased nAChRs expression

  • increased resistance to apoptosis

Effect of maternal smoking on inflammatory markers IL-1β, IL-1R and IL6:

  • IL1-β mRNA was not changed

  • IL-IR mRNA increased

  • IL6 mRNA was stimulated in later development

Neurotransmitters affected by smoking

  1. Acetylcholine: is associated with wakefulness, anger, and thirst and stimulated hormone secretion

  2. Norepinephrine: excitatoru important for focus of the CNS

  3. Serotonin: inhibitory used for mood stabilizer, depleted by stimulants

Synaptoc Proteins in the Synapses

  • reduced after exposure to Tobacco smoke

  • Synapsins: regulation of the vescicle pool at presynaptic terminals , elongation of axons and synaptic vesicle docking

  • Synaptophysin: calcium binding protein associated with presynaptic vesicles

  • PSD-95: scaffolding protein in excitatory postsynaptic density; regulated synaptic strength