Central nervous system neuronal loss

The condition is caused by deficiencies of palmitoyl protein thioesterase 1 (PPTl) (or tripeptidyl peptidase 1 (TPPl) and possibly other enzymes resulting in the same clinical presentation of NCL (for Aeural Ceroid Lipofuscinose)). PPTl cleaves long-chain fatty acids from S-acylated proteins within the lyso-some (Lu et al., 1996). How the loss of this activity causes the death of central nervous system neurons is not known. 

Central nervous system effects predominate in acute exposures at massive doses, whereas peripheral neuropathy is more common with lower doses.After cessation of exposure to acrylamide, most cases recover, although the course of improvement can extend over months to years and depends on the severity of exposure. Because peripheral neurons can regenerate and central axons cannot, severely affected individuals may still experience residual ataxia, distal weakness, reflex loss, or sensory disturbance. 

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter. For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines. 

Neurotoxicity Cells of the central nervous system, CNS (brain and spinal cord) and the peripheral nervous system (nerves outside the CNS) Neuronopathies (neuron injury) Axonopathies (axon injury) Demyelination (loss of axon insulation) Interference with neurotransmission... 

Among the catecholamines, dopamine has long been of interest to both chemists and neuroscientists. It is one of the most important neurotransmitters and is ubiquitous in the mammalian central nervous system[5]. It modulates many aspects of brain circuitry in a major system of the brain including the extra pyramidal and mesolimbic system, as well as the hypothalamic pituitary axis[6]. It also plays a crucial role in the functioning of the central nervous, cardiovascular, renal and hormonal systems[4], A loss of dopamine containing neurons or its transmission is also related to a number of illnesses and conditions including Parkinson s disease, schizophrenia, motivational habit, reward mechanisms and the regulation of motor functions and in the function of the central nervous, hormonal and cardiovascular system[5,18,19]. It is therefore of interest to measure dopamine in the extracellular fluid in animals to order to monitor neurotransmission processes and correlate neurochemistry with behavior[19]. 

Commercially available P. ginseng products have been reported to have stimulant effects on the central nervous system (CNS) in humans (34) (see Section 5). In animal models, ginseng extracts have been shown to have CNS-stimulant effects (35). Ginsenoside Rgl inhibits neuronal apoptosis in vitro (35), and ginsenoside Rbl reverses short-term memory loss in rats (4). 

Some cases also show dyscontrol of autonomic functions mediated by the potentially affected central noradrenergic sympathetic nervous system, with losses of norepinephrine neurons of the locus coeruleus (4). There can also be variable late neuropsychiatric disturbances that sometimes progress to a debilitating state and eventual fatality (2, 5, 6). Dementia is about six times more frequent in elderly patients with PD than without it (5). Major depression also occurs in PD, and psychosis is sometimes associated with DA agonist therapy (5-7). Mortality is 2-5-times higher among PD patients than in age-matched non-affected persons, and life expectancy is greatly reduced (8). 

Since iron is involved in many central nervous system processes that could affect infant behaviour and development, iron deficiency has adverse effects on brain development, both pre- and post-natal. In various epidemiological studies, it is reported that children with iron-deficiency anaemia have poorer performances on tests of some specific cognitive function. Animal experiments have identified some of the defects of reduced iron availability on brain function, which include post-translational changes (which result in a failure of iron incorporation into protein structures which are subsequently degraded), vulnerability of the developing hippocampus (with loss of the neuronal metabolic marker cytochrome c oxidase), and altered dendritic stmcture. Iron deficiency will also have a direct effect on myelin, including a decrease in myelin lipids and proteins, as well as neurotransmitter systems, since iron... 

GSK-3P deficiency in genetically modified mice is embryonic lethal, supporting a potentially important function during embryonic development where GSK-3 affects the Wnt and NFkB signalhng pathways [7]. These findings also suggest that GSK-3a cannot compensate for the fimction of GSK-3, further supporting distinct functions for the two isoforms. Selective overexpression of GSK-3 in the central nervous system (CNS) causes a reduction in brain and spinal cord volume in conjunction with reduced dendritic mass in the spinal cord. The reduction in brain voliune is accompanied by an increased neuronal density, but no apparent loss of neurons [8]. 

Alzheimer s disease is associated with a progressive loss of cholinergic neurons in the brain that results in memory disturbances and cognitive dysfunction. One strategy for the treatment of Alzheimer s patients has been the use of acetylcholinesterase (AChE) inhibitors such as rivastigmine to enhance choUnergic activity in the central nervous system,... 

Seizure—Paroxysmal disorder of central nervous system, characterized by abnormal neuronal discharges with or without loss of consciousness. They vary in cause, presentation, consequences, duration, and management. 

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