dementia/Mental health Flashcards
aspects of alzheimers
60-80% of all cases
- impaired cognition, perturbation in brain energy metabolism
- hippocampus first region to suffer damage
Two aspects of the patholody of dementia
Neurofibrillary tangels
- hyperphosphorylated tau proteins
- coorelated to progression
Amyloid b plaque
- pro. fragments built up between neurons
-interfere w synaptic signaling
(microglia may be activated to clean up but can cause release of tnfa and IL6)
neuroinflammation in dementia causes
activated microglia
-TNFa, IL6, increase ROS
Apolipoprotien E4
- mitochondrial dysfunction
- inhibits neutrite outgrowth
- enhances tau phosphorylation
mito dysfunction in brain
-too much ca in mito opens MPTP and releases cytochrome c + A1F which leads to apoptosis
ROS and brain
- brain is extremely suseptible to oxidative stress (uses alot of mito therefor big risk of ROS prod
- brain is made of poly unsaturated fats which ROS attacks easily
How mito dysfunction leads to apoptosis
oxidative stress–> MTDNA mutations–> disruptions in ca homeostasis–> MPTP opening–> releases apoptic signaling
Brain hypometabolism (3 aspects)
- decreased GLUT1/3 expression
- cant get enough glu to brain= state of stress= ROS prod=neural apoptosis - Decreased cerebral BF
- periferal obesity=hypertension
- -which puts strain on CV system - Impaired insulin signaling
Pathway of systematic inflamation in brain
- Peripheral obesity-> adiposity
- chronic low grade inflamation
- releases cytokines (TNFa, IL6)
- pass blood brain barriers (activates microglia
- Chronic neuroinflamation
- Activates MAPKs
MAPKs effect
- increase neuronal apoptosis
- increase BACE1 (regulates prod of AB)
- Phosphorylation of APP by JNK
TNFa and JNK affects
- directly inhibits IRS1
- leads to impaired insulin signaling
Exercise effects on brain
Increase NOS, eNOS, increase BDNF, IGF1, Antioxidants
all lead to- increase cerebral BF, angiogenesis, neuroplasticity, lowers inflamation, increasess dendric density
BDNF effects on brain
- proliferation of hippocampal neurons
- enhances synaptic plasticity/ neurogenesis
- improves learning/memory
- inhibits neuroinflamation + apoptosis
IGF1 effects on brain
- proliferation of hippocampal neurons (more synapses= more buffered against the plaques, can afford to lose more)
- improves insulin sensitivity
- increase BDNF
Irisin effects on brain
- proliferation of hippocampal neurons
- enhances synaptic plasticitu and neurogenesis
- browning of WAT
- Stim AKT/MTOr path
Exercise training on mitochondria
- increase antioxidant capacity
- decrease apoptic markers
- increase biogenesis
- increase HSP
- reduce BACE 1 content
depression symptoms
- persistant feelings of sadness, hopelessness, worthlessness
- irritability, frusturation
- loss of interest
- fatigue