Neuronal Cell Deterioration

Neuronal cell deterioration Neuronal cell death... 

Neurodegeneration refers to the processes whereby damaged neuronal cells deteriorate or degenerate and eventually die. 

Some mental disorders also appear to result from disruption of the natural flow of neurotransmitters between neurons. For example, scientists now believe that the disorder known as Parkinson s disease may result from a deficiency of the neurotransmitter dopamine. Parkinson s disease is characterized by muscular rigidity, tremor while the person is at rest, difficulty in initiating movement (a condition known as hradykinesia), slowness of voluntary movement, difficulty with balance, and difficulty with walking. When the neuronal cells that produce dopamine begin to deteriorate, they release less of the neurotransmitter the normal flow of dopamine between cells is reduced and disruptions of normal nerve patterns develop, as evidenced by the symptoms described. 

The mechanism of the neurological symptoms in Parkinson s disease was discovered from the ability of reserpine to cause akinesia in humans by the depletion of central catecholamine stores. The dopamine levels in patients who died from parkinsonism were found to be extremely low because of deterioration of the dopaminergic neuronal cell bodies and the pathways connecting the substantia nigra with the corpus striatum. 

BD and other forms of NCL are relatively rare, occurring in an estimated two to four of every 100,000 live births in the US [www.ninds.nih.gov]. There is currently no specific treatment for BD and current therapy simply alleviates the symptoms of the disease. Anticonvulsant drugs alleviate the associated seizures, and occupational therapy helps individuals compensate for the loss of vision, physical and mental abilities. Because BD involves the deterioration of neuronal cell tissue, it is a candidate for cellular therapy. 

Depletion of NE may cause deterioration of AD pathology in different animal models (Heneka et al., 2002) (Kalinin et al., 2007) (Heneka et al., 2006). Animals who received amyloid-P injections into the cortex and chronic DSP4 to induce LC neuronal cell death led to induction of inflammatory changes within the CNS of AD animals. An increase in iNOS, IL-ip, and IL-6 expression compared to control animals was measured in the brain. However, COX-2 expression was transiently reduced in the AD animals. Co-injection with NE or the P-adrenoreceptors agonist isoproterenol attenuated the inflammatory response in the amyloid-P and DSP4 injected animals. The inflammatory response caused by NE depletion seems to be due to reduced levels of NF-kB inhibitory IkB proteins and of heat shock protein 70 (Heneka et al., 2003). 

PD affects approximately one million Americans (1% of people over 60 years of age). The average age of onset is 60 years of age, and PD is fairly uncommon in those under age 40. The etiology of PD is unknown, but genetic predisposition, environmental factors, or combinations of these have been proposed to explain why nerve cells in the substantia nigra deteriorate. About 15% of patients with PD have a first-degree relative with the disease. The pathogenesis of cell death (neuron degeneration) may be due to oxidative stress, mitochondrial... 

The neuronopathic symptoms described above are caused by substances that attack and destroy the cell bodies of neurons. Another class of toxic effects occurs as the result of deterioration of nerve axons and its surrounding myelin. Symptoms resulting from this effect are called axonopa-thies. A classic toxicant cause of axonopathies is that of y-diketones, most commonly 2,5-hex-anedione ... 

Most animal studies report irreversible neuronal damage, including cell death, after relatively brief exposure to neuroleptics. Of great importance, animal studies with longer durations of exposure to neuroleptics— 1 year (Pakkenberg et al., 1973), 8 months (Jeste et al., 1992), and 36 weeks (Nielsen et al., 1978)—show the expected neuronal deterioration in the basal ganglia. 

Studies from several laboratories have shown that T cells patrol the healthy CNS, but do not accumulate there. The recent data suggest that, in the event of an acute injury or chronic neurodegenera five condition, T cells are recruited by and accumulate in the CNS (Hirschberg et al., 1998 Moalem et al., 1999a), where they might rescue neurons from degeneration if the damage caused by the toxic biochemical environment is not yet irreversible moreover, the recruited T cells will prevent further deterioration. It is also possible that this autoimmune protective mechanism also operates when the... 

Degenerative Diseases. Xenotransplantation trials are taking place with Parkinson s disease, a neurode-generative disorder that causes progressive deterioration in the cells of the brain. The trials involve patients who have had fetal pig neurons implanted into their brains. The hope is that these cells will help reverse the damage caused by their disease. Xenotransplantation is therefore a potentially useful therapy in cases in which whole-organ transplantation is not suitable and for which no effective treatment exists. 

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