Dendritic and Synaptic Losses

The normal organization of neuronal networks is maintained in many healthy elderly, but for some older individuals, the number of dendrites and dendritic spines may be reduced (the so-called "denudation" of neurons). For example, the cortex of a typical young individual shows large pyramidal cells with abundant dendrites rich in dendritic spines. A corresponding zone, in a typical old individual, shows a striking loss of dendrites and spines (40). Dendrites function as receptor membranes of the neurons and represent the sites of excitatory or inhibitory activity. Dendritic spines, tiny and numerous on each dendrite, amplify such activity, and by doing so, control increases in synaptic calcium transport that may serve for induction of information storage. Loss of dendrites and spines results in neuronal isolation and failure of interneuronal communication. With reduced dendrites, synapses are lost, neurotransmission is altered, and communication within and without the nervous system is impaired. However, further reflecting the persistence of plasticity of the brain, it is also known that increased density of dendritic growth and length of individual dendrites may occur in different brain areas—including the cerebral cortex—in humans in their seventies (41,42).

Inasmuch as dendrites undergo a certain degree of continuous renewal, the denudation of the neurons may not be a true loss, but rather a slowing of the renewal process. When the loss of dendrites is viewed in a network of neurons, the consequences of diminished connectivity become apparent (43,44). In normal aging, with continued environmental stimulation, dendritic loss may be minimal, absent, or even supplemented with a degree of dendritic outgrowth. In dementia (Chapter 7), the dendritic loss is severe and progressive (Fig. 4).

The decreased number of synapses in discrete areas of the aging brain follows the corresponding loss of dendrites and dendritic spines. Alterations in synaptic components— membrane, vesicles, and granules—have been variously reported. The "reactive synaptogenesis" or axonal sprouting that follows the loss of a neuron is not entirely lost but decreases with aging (8). Reactive synaptogenesis represents a compensatory reaction to neuronal loss or damage and is characterized by an increase in the number of synaptic contacts provided by the nearby neurons. Such a compensation, although less efficient, can persist in the old brain.

As "hyperconnectivity" resulting from neurologic causes (e.g., temporal epilepsy) may lead to heightened attention, perceptions, memories, and images, progressive loss of interneuronal communication may cause a downward shifting of neurologic and mental processes. Relatively impaired CNS function in normal old age may be due to a multifactorial "hypoconnectivity" and increasing "rigidity" (consequent to vascular and metabolic alterations) rather than to regional and moderate neuronal losses. Several functions [e.g., electrocardiogram (ECG), electroencephalography (EEG), pulsatile hormonal secretions] that were formerly thought to be relatively periodic show a complex type of variability reminiscent of

FIGURE 4 Semischematized drawing summarizing the changes that may occur in pyramidal neurons of the aging human cerebral cortex. Sequence A, B, C follows the changes that may occur in the normal aging cortex under the effects of continued physical and cognitive "challenge" in the probable presence of continuing small amounts of neuronal loss. Increasing dendritic growth, especially in the peripheral portions of the basilar dendrites, reflects dendritic response to optimal cortical "loading," plus presumed supplementary growth to fill neurophil space left by dendrite systems of those neurons that die. Sequence A, D, E, F epitomizes the progressive degenerative changes that characterize senile dementia of the Alzheimer type and includes progressive loss of dendritic spines and dendritic branches culminating in death of the cell. Basilar dendrite loss precedes loss of the apical shaft. Sequence A, D, G, E, F represents a unique pattern of deterioration of the dendrite tree found only in the familial type of presenile dementia of AD. During the period of dendritic degeneration, bursts of spine-rich dendrites in clusters appear along the surface of the dying dendrite shafts. Such changes have been seen in neocortex, archicortex (hippocampus), and cerebellar cortex. The cause and mechanisms of these eruptive attempts at regrowth, even as the neurons are in a degenerative phase, are unknown. Abbreviation. AD, Alzheimer's disease. Source. Courtesy of Dr. A. B. Scheibel.

"chaos" (i.e., unpredictable behavior arising from internal feedback from interconnected loops of nonlinear systems) (45). Aging, by reducing the interconnectedness and complexity of these systems, might diminish the plasticity and dynamics of brain processes (46-48).

A number of other harmful changes in brain structure, usually quite moderate and with considerable individual variability, may occur in normal aging. These include alterations in the axons that may contribute to disruption of neural circuitry, demyelination, axonal swelling, and changes in the number of neurofilaments and neurotubules. Changes occurring with aging in the neural cytoskeleton [as in neurofibrillary tangles (NFTs)], accumulation of amyloid proteins [as in neuritic plaques (NPs)], impaired cell survival (reduced antiapoptotic synaptic proteins), alterations in the cerebrospinal fluid composition and volume, and other changes are discussed below and in ■ Chapter 7 in relation to their repercussions (e.g., dementia).

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment