Neuron abnormal

FIGURE 2.7 Two-photon fluorescence microscopy of amyloid plaque (red) and surrounding neurons (green) in the brain of a mouse model of Alzheimer s. Numerous neuronal abnormalities, including swelling and decreased densities of spines (arrow in c), could be detected. 

Being at the center of a complex network linking immune response and inflammatory reactions, it is not surprising that imbalances in KP metabolites lead to pathophysiological consequences. In Drosophila (Drosophila melanogaster), genetic deletions of individual KP enzymes resulted in neuronal abnormalities... 

Moore, M.W., Klein, R.D., Farinas, I., Sauer, H., Armanini, M., Phillips, H., Reichardt, L.F., Ryan, A.M., Carver-Moore, K. and Rosenthal, A. (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382 76-79. 

Related to changes In excitability of spinal and supraspinal neurons Abnormal sensations associated with hyperalgesia... 

Comment A common association of type-2 fiber atrophy (discussed in Chapter 1) is an aspect of a lower-motor-neuron abnormality resulting in functional "dysinnervation," as may be part of the pathogenic mechanism in this patient. Note that routine diagnostic EMG cannot quantify the size of the type-2 muscle-fiber fast-twitch units because they are activated only by vigorous contraction, whereas slow-twitch type-1 motor-units are activated by... 

Hoffrnan, E.P., Kunkel, L.M. (1989). Dystrophin abnormalities in Duchenne/Becker muscular dystrophy. Neuron 2, 1019-1029. 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

That an episode arises and spreads from the synchronous as well as excessive discharge of a group of neurons (focus) means that not only must those neurons be in some way predisposed to so discharging but they can also recruit neurons that are otherwise normal. How that discharge manifests itself, i.e. which type of epilepsy occurs, will depend not only on where the abnormal focal neurons are located but also to what extent the activity they initiate can and does spread through the brain. There are consequently a number of different forms of epilepsy, i.e. the epilepsies. 

The dendrites of neurons adjacent to those which degenerate also show extensive growth and sprouting which could facilitate abnormal and disorganised synaptic transmission and cause hyperactivity. It is also known that the dendrites of cells around an alumina focus in monkeys, as well as in human epileptic brain, lose their spinous processes, which might contribute to the paroxysmal discharge by facilitating the spread of depolarisation to the neuron soma. Certainly an increase in the number of Na+ channels on the dendrites of spinal motoneurons, which would facilitate the occurrence of reactive dendritic Na+ spikes, has been seen after axotomy. 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

---