Regeneration, Repair, and Plasticity Chapters 6, 7, 8, 10 P.S. Timiras

The Theories of Aging Decay of mitochondria Cell senescence Oxidative Stress Shortening of telomeres Evolutionary theories Disposable soma Antagonistic pleiotropy Mutation accumulation System theories Neuroendocrine Immune Rate of living

Neuroendocrine Theory The Nervous System Central (brain, spinal cord) Peripheral (whole-body innervation) Autonomic (regulation of visceral organs, tissues) The Endocrine System Hypophysiotropic hormones: ADH Oxytocin Hypothalamus Limbic system Pituitary hormones: Gonadotropins Adrenal steroids Thyroid hormones Growth hormone Prolactin Pancreas: Insulin GI hormones

Brain Plasticity and CNS Regenerative Potential From the beginning of the 20th Century until the 1990s, it was stated that neurons DID NOT proliferate. The fact that they COULD NOT proliferate did not exclude the possibility of proliferation under “specific conditions.” In fact, the CNS has a considerable regenerative potential depending on the special conditions of the neuronal environment. From the beginning of the 20th Century until the 1990s, it was stated that neurons DID NOT proliferate. The fact that they COULD NOT proliferate did not exclude the possibility of proliferation under “specific conditions.” In fact, the CNS has a considerable regenerative potential depending on the special conditions of the neuronal environment.

Neurons that may proliferate into adulthood include: Progenitor “precursor” neurons lining the cerebral ventricules Neurons in the hippocampus Neurons usually “dormant” with potential for neuron and glia proliferation Neuroglia (astrocytes, oligodentrocytes) and microglia (immune cells) with the ability to perpetually self renew and produce the three types of neural cells Progenitor “precursor” neurons lining the cerebral ventricules Neurons in the hippocampus Neurons usually “dormant” with potential for neuron and glia proliferation Neuroglia (astrocytes, oligodentrocytes) and microglia (immune cells) with the ability to perpetually self renew and produce the three types of neural cells

Regenerative potential depends on changes in whole body and neural microenvironment Whole body changes: –Physical exercise –Appropriate nutrition –Good circulation –Education –Stress –others Whole body changes: –Physical exercise –Appropriate nutrition –Good circulation –Education –Stress –others Neural microenvironment changes: –Brain metabolism (oxygen consumption, free radicals, circulatory changes) –Hormonal changes (estrogens, growth factors, others) –others

Death Rates in 1986 among Persons Years Old in Selected Education and Income Groups According to Race and Sex. ________________________________________________________ GroupWhiteBlack Men WomenMenWomen deaths per 1000 Education- yr Completed School College  Income-$ <9, ,000-14, ,000-18, ,000-24, >25, ______________________________________________________________________________________ Pappas, G., Queen, S., Hadden, W., and Fisher, G. The increasing disparity in mortality between socioeconomic groups in the United States, 1960 and N. Engl. J Med. 329, , 1993.

Proportion of Remaining Life Expected to be Lived with a Disability in Activities of Daily Living and Death Rates ________________________________________________________ At Age At Age At Age Death Rates per 1,000 White men Low education Higher education White women Low education Higher education Black men Low education Higher education Black women Low education Higher education ________________________________________________________________________ From: Guralink, J.M., et al., Educational status and active life expectancy among older blacks and whites, N Engl. J Med., July 8, 1993, Vol. 29:

Mechanisms of Education Effects Better access to recreational activity Better nutrition Higher income Responsibility to health behaviors No alcohol intake No smoking Increased brain reserve capacity? More dendritic branching, cortical synapses?; Better cerebral blood flow?; Better neural cell efficiency, adaptability, redundancy, survival and growth Better access to medical care

Fig. 7-4: “Denudation” of the neurons. Changes in pyramidal neurons of the aging human cerebral cortex

Anatomical Correlates of Educational Protective Effects* Educational Level Increasing levels from 12 grades Anatomical Correlate total dendritic length mean dendritic length dendritic segment count Location Pyramidal cells in layer 2,3 of Wernicke’s area Variable Studied Gender Hemisphere Education Personal history Hormonal Correlate Thyroid Hormones dendritic number and length Glucocorticoids reactive synaptogenesis ______________ * From Jacobs et al., J Comp. Nuerol., 327, 97, 1993