Hanipsych, bdnf in alzh.

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  • SOURCES: NCBI, ACCESSION # X60201; SHINTANI, ET AL. 1992; MURER, ET AL. 2001; MOWLA, ET AL. 2001
  • Hariri et al J Neurosci 2003
  • Hanipsych, bdnf in alzh.

    1. 1. BDNF May Protect Against Alzheimer's Prof. Hani Hamed Dessoki, M.D.Psychiatry Prof. Psychiatry Chairman of Psychiatry Department Beni Suef University Supervisor of Psychiatry Department El-Fayoum University APA member
    2. 2. Agenda Introduction
    3. 3. Brain-Derived Neurotrophic Factor (BDNF) BDNF Important for neurons to grow and connect to each other, and contributes to long-term potentiation Both are part of "neural plasticity" = the ability of the brain to change as a result of experience Shown in aplysia that long term memories cannot be formed when BDNF is blocked (University of California - Irvine (2006, September 6). Proteins Necessary For Brain Development Found To Be Critical For Long-term Memory. ScienceDaily. Retrieved May 5, 2011, from http://www.sciencedaily.com/releases/2006/09/060905225522.htm)
    4. 4. Introduction  Higher blood levels of brain-derived neurotrophic factor (BDNF) appear to protect against Alzheimer's disease (AD) and other types of dementia.  Blood levels of BDNF might be used to help predict risk for AD in older adults. Or giving BDNF to older people might prevent or counter AD symptoms.  BDNF targets the cortical cells themselves, preventing their death, stimulating their function and improving learning and memory.
    5. 5. Introduction  Higher serum BDNF levels may protect against future occurrence of dementia and AD.  BDNF has a role in the biology and possibly in the prevention of dementia and AD, especially in select subgroups of women and older and more highly educated persons.
    6. 6. Dementia DSM-IV-R  Memory and other cognitive deficits  Impairment in social and occupational functioning Degenerative dementias  Intrinsic to the nervous system  Affects the CNS selectively Nondegenerative dementias  Diverse etiologies
    7. 7. Dementia Alzheimer’s disease  Most prevalent form of dementia  Neuritic Plaques  Found in the cortex  Positively correlated with cognitive decline  Amyloid surrounded by degenerative cellular fragments  Paired Helical Filaments  Found in the cortex and hippocampus
    8. 8. Alzheimer's disease is characterized by a build-up of proteins in the brain. Though this cannot be measured in a living person, extensive autopsy studies have revealed this phenomenon. The build-up manifests in two ways: Plaques– deposits of the protein beta-amyloid that accumulate in the spaces between nerve cells Tangles – deposits of the protein tau that accumulate inside of nerve cells
    9. 9. Microscopy image of a neurofibrillary tangle, conformed by hyperphosphorylated tau protein.
    10. 10. Dementia Alzheimer’s disease  Neocortical Changes  Shrinkage of the cortex; not uniform
    11. 11. Dementia Alzheimer’s Disease  Neurotransmitter changes  Reduction in two or more transmitter systems  ACh, Noradrenaline, DA, 5-HT, and glutamate receptors
    12. 12. Putative Causes of Alzheimer’s Disease Genetics Trace Metals  Increased concentration of aluminum Immune Reactions  Antibrain antibodies that cause neuronal degeneration
    13. 13. Putative Causes of Alzheimer’s Disease Blood Flow  Decrease in blood flow to the brain Abnormal Proteins  Increased production of abnormal proteins that accumulate in the brain
    14. 14. Brain Derived Neurotrophic Factor and neuronal plasticity increases cortical neuron survival sculpts glutamate innervation patterns increases synaptic efficacy of glutamate modulates LTP in hippocampus expression increased during spatial memory expression increased by antidepressant treatments genetic associations: Alzheimers Disease, Parkinson’s Disease, bipolar disorder, schizophrenia
    15. 15. The BDNF Gene 11p13 CHROMOSOME 11 PROMOTER 1 297 468 492 11p14 681 1040 1353 BP 5´ START CODON MAY BE EXTRACELLULARLY ACTIVE AT TrkB RECEPTORS G492 → A492 ⇓ Val66 → Met66 CLEAVED IN ENDOPLASMIC RETICULUM Val66 → Met66 SIGNAL TRUNCATED proBDNF (28 kDa) PEPTIDE ACTIVITY UNKNOWN OR STOP CODON proBDNF (32 kDa) CLEAVED IN TRANS-GOLGI NETWORK AND/OR IMMATURE VESICLES Val66 → Met66 SIGNAL PEPTIDE MATURE BDNF (14 kDa) ESSENTIAL ROLE IN DEVELOPMENT, SURVIVAL AND FUNCTION OF NEURONS
    16. 16. BDNF: How do we get there from here ? BDNF: Cells: val66met polymor- Intracellular trafficking phism and regulated secretion bipolar disorder, schizophrenia Alzheimer’s Disease, antidepressant effects Behavior: Systems hippocampal complex functional processing of interactions and emergent memory phenomena
    17. 17. BDNF val/met genotype, hippocampal activation and prediction of recognition accuracy Variance in memory performance variability of recall 5% 25% 25% 5% hippocampal activation during retrieval interaction of BDNF genotype and hippocampal activation during encoding Hariri et al J Neurosci 2003
    18. 18. Dietary and Behavioral Neurohormesis Dietary Restriction Physical Exercise Cognitive Enrichment Cellular Stress Response serotonin Neuroprotection Neurogenesis Synaptic plasticity BDNF Resistance to Neurodegenerative Disorders Resistance to Diabetes and Cardiovascular Disease SSRI Improved Glucose Metabolism
    19. 19. Overeating: Our Nation’s Biggest Health Problem Cardiovascular disease Diabetes Cancers Stroke Neurodegenerative disorders? Reduced lifespan Disease AGING Genes Exercise Diet Mental Health Reduced Lifespan Average Lifespan Maximum Lifespan Dietary Restriction Increased insulin sensitivity Improved cardiovascular risk factors Decreased tumor incidence Increased cellular stress resistance Enhanced neuronal plasticity Disease resistance Increased lifespan
    20. 20. DIETARY LIPIDS AND AD Dietary cholesterol, saturated fats and trans fats may increase the risk of AD (Notkola et al., Neuroepidemiology. 1998; 17:14-20.; Evans et al., Neurology. 2000; 54:240-2.; Morris et al., Arch Neurol. 2003; 60:194-200), High cholesterol diet increases amyloidogenic processing of APP and Abeta accumulation in brain cells (Sparks et al., Exp Neurol. 1994; 126:88-94; Howland et al., J Biol Chem. 1998; 273:16576-82; Refolo et al., Neurobiol Dis. 2000; 7:321-31; .George et al., Neurobiol Dis. 2004; 16:124-132) Statins may lower the risk of AD (Wolozin et al., Arch Neurol. 2000; 57:1439-43; Jick et al., Lancet. 2000; 356:1627-31) Statins may reduce Abeta levels in AD patients (Simons et al., Ann Neurol. 2002; 52:346-50) DHA (docosahexaenoic acid) levels are decreased in AD and DHA suppresses amyloid an neuronal pathology in APP mutant mice (Tully et al., Br J Nutr. 2003; 89:483-9; Calon et al., Neuron. 2004; 43:633-45)
    21. 21. BDNF Cheng, A., S. Wang, M. S. Rao and M. P. Mattson (2002) Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev. Biol. 258: 319-333.. Lee, J., K. Seroogy and M. P. Mattson (2002) Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J. Neurochem. 80: 539-547.
    22. 22. Exercise and brain blood vessel growth In people ages 60-80, those who aerobically exercised 3+ hours a week over the course of 10 years showed: An increase in the number of large blood vessels in the cerebral region of the brain An increase in blood flow in the 3 major cerebral arteries The cerebral area controls consciousness, memory, initiation of activity, emotional response, language and word associations Narrowing and loss of blood vessels may be associated with cognitive decline Rahman, Feraz, et. al (2008). Study presented at Radiological Society of North America; UNC Chapel Hill researchers.
    23. 23. Effects of Aerobic Exercise on Brain  Delay or reverse cerebral structural & functional changes*  Delay beta-amyloid accumulation*  Improves memory*  Increases brain-derived neurotrophic factor (BDNF): a neurotrophin associated with learning, cell health
    24. 24. Effects of Aerobic Exercise on Brain Protects against hyperinsulinemia and insulin resistance Increased dopamine levels in the brain Increases cerebral vasculature and blood flow
    25. 25. Future Directions Blood levels of BDNF might be used to help predict risk for AD in older adults. Giving BDNF to older people might prevent or counter AD symptoms (Lithium???). Psychiatric News , 2013
    26. 26. Take Home Message Higher blood levels of brain-derived neurotrophic factor (BDNF) appear to protect against Alzheimer's disease (AD) and other types of dementia.

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