Post-mortem studies

Since these neurons form the dopaminergic nigrostriatial tract (Fig. 7.1) it is not surprising that PD patients also show a loss of striatal DA. This was first detected in post-mortem studies in 1960 by Hornykiewicz and numerous studies since have shown that not only is PD associated with and presumably caused by a loss of striatal DA, but at death that loss actually reaches more than 80%. Within the striatum DA loss is greater in the putamen which has predominantly motor links with the cortex than in the caudate mucleus with its connections to cortical association areas. 

Dr. Rebec also said that the brains on post mortem studies of schizophrenics tended to be mushy and to have very low levels of ascorbic acid in their constituent tissue. 

In this book it is suggested that one possible cause of death in prolonged starvation is severe hypoglycaemia. This may be due to a lack of amino acid precursors since almost all the body protein has been broken down. Alternatively, the fat store in the body has been totally depleted, so that the plasma fatty acid level will be close to zero. Consequently, there will be no fatty acid oxidation in the liver and therefore little or no ATP generation to support gluconeogenesis. Post-mortem studies on individuals who have died of starvation show that the fat stores are totally depleted. This topic is discussed further in Chapter 16. 

Post mortem studies have shown that the level of polynn-satnrated fatty acids in some areas of the brain is decreased (particnlarly the hippocampus, striatum and cortex). In addition, it is known that the fluidity of membranes in... 

The only known change in neurotransmitter metabolism so far detected is a deficiency of acetylcholine in the brain. This has been shown in post-mortem studies on the brains of patients with Alzheimer s disease. Some success in reducing the symptoms of the disease has been obtained with drugs that inhibit the activity of acetylcholinesterase leading to an increase in the acetylcholine concentration, but the improvement is minimal so that its use is controversial. 

Thus when the results of the studies on platelets, lymphocytes, changes in cerebrospinal fluid metabolites of brain monoamines and the post-mortem studies are taken into account it may be concluded that a major abnormality in both noradrenergic and serotonergic function occurs in depression, and that such changes could be causally related to the disease process. 

While these proposals provide useful and testable hypotheses, they are based on slim evidence from post mortem neurochemistry of schizophrenia. Since the deficits in GABAergic markers may be interpreted as demonstrating neuronal hypofunction rather than cell loss, they could equally be ascribed to a consequence of, rather than a cause of, glutamatergic abnormalities. It would be valuable to identify temporal changes in neurochemistry over the disease course, rather than end-stage information that most post-mortem studies inevitably provide, as well as more information from individuals at risk for schizophrenia. 

A post-mortem study on the brains of alcohoUcs showed a modest increased binding for [3H]glutamate and [3H]CGP-39653—a competitive NMDA receptor antagonist (Freund and Anderson 1996). In humans with a history of alcohol abuse, an increase in immunoreactivity toward AMPA GluR2 and GluR3 subunits was also found (Breese et al. 1995). In rodents lacking functional... 

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Reinikainen KJ, Paljarvi L, Huuskonen M, Soininen H, Laakso M, Riekkinen PJ (1988) A post-mortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer s disease. J. Neurol. Sci. 84 101-116. 

Forrest, F. M., Forrest, I. S., Roizin, L. (1963). Clinical, biochemical and post mortem studies on a patient treated with chlorpromazine. Revue Agressologie, 4, 259-265. Fowler, M. (1992). Educator s manual A project of the CH.A.D.D. National Education Committee. Plantation, FL CHADD. 

Falkai P, Bogerts B, Greve B, Pfeiffer U, Machus B, et al. 1992. Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study. Schiz Res 7 23-32. Falkai P, Bogerts B, Schneider T, Greve B, Pfeiffer U, et al. 1995. Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study. Schiz Res 14 161-176. 

Reynolds GP, Brown JE, McCall JC, Mackay AVP (1992) Dopamine receptor abnormalities in the striatum and pallidum in Tardive Dyskinesia. A post mortem study. J Neural Transm 87 225-230. 

Apart from the classic biomarkers, i.e., tau protein(s) and their phosphorylated forms as well as AP peptides, several other candidate biomarkers have been tested, as recently and extensively reviewed by Frank et al. (2003). Neuronal thread proteins (NTPs) are a family of molecules expressed in the CNS. In a post mortem study, brains of AD patients expressed significant increases of NTP immunoreactivity (de la Monte and Wands, 1992). Following this finding, CSF examination for NTP revealed increased concentration of NTP which correlated tvith progression of dementia and neuronal degeneration (de la Monte et al, 1992). Sensitivity and specificity of this protein as a possible marker of AD, however, have not been determined in a large enough number of patients. 

Pakkenberg B (1987) Post-mortem study of chronic schizophrenic brains. Br J Psyclriati y 151 744—752. 

Coombs DW, Fratkin JD, Meier FA, Nierenberg DW, Saunders RL. Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study. Pain 1985 22(4) 337-51. 

Dettmeyer R, Wessling B, Madea B. Heroin-associated nephropathy - a post-mortem study. Forensic Sci Int 1998 95 109-116. 

Small, papillary, usually multiple tumors of the renal pelvis and ureters are also one of the characteristic findings (Figure 2B]. In post-mortem studies tumors were reported in 8-50% of cases [74, 79]. 

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