Hippocampus atrophy

Smaller hippocampus, atrophy greater if depressed longer... 

Breyhan H, Wirths O, Duan K et al (2009) APP/PSIKI bigenic mice develop early synaptic deficits and hippocampus atrophy. Acta Nemopathol 117 677-685... 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

As a possible consequence of direct neurotoxic effects of sustained hypercortisolism, hippocampal atrophy has now repeatedly been reported for depressed patients (Sheline et ah, 1996 Bremner et al., 2000a). Hippocampal atrophy may be associated with disinhi-bition of CRF secretion and further increases in cortisol secretion, which in turn may further damage the hippocampus. Impaired inhibition of the HPA axis is also evidenced by nonsuppression of cortisol by dexame-thasone and decreased GR numbers in depressed patients both findings parallel those in maternally separated rats. 

Horn, R., Ostertun, B., Fric, M., Solymosi, L., Steudel, A., et al. (1996) Atrophy of hippocampus in patients with Alzheimer s disease and other diseases with memory impairment. Dementia 7, 182-186. 

VVliilc current theories about the actions of antidepressants are best viewed as tentative, recent work on tlic ncurobiology of depression has provided some exciting new insights. A link has been known to exist ben ccn depression (and also chronic stress and anxiety) and atrophy and cell loss in the hippocampus. Research by several researchers (e.g., Duman, 2004 Duman, Nakagawa, Malberg, 2001 Malhcrg,... 

Eisch, Ncstler, Duman, 2000 Santarclli et al., 2003) has demonstrated that antidepressant treatment increases neurogenesis, or new cell growth, in the hippocampus. This neurogenesis may block or reverse the effects of depression on hippocampal neurons. Further, the new cell growth appears to take several weeks to occur, and this may account for the fact that antidepressant medications typically take several weeks to exert their action. The findings suggest that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the atrophy and loss of hippocampal neurons associated with depression. 

Neuronal loss is a pathognomonic finding in AD and the final common path of multiple pathogenic mechanisms leading to neurodegeneration in dementia. Atrophy of the medial temporal lobe, especially the hippocampus and the parahippocampal gyrus, is considered to be the most predictive structural brain biomarker for AD. The medial and posterior parts of the parietal lobe seem to be preferentially affected, compared to the other parietal lobe parts [19]. 

Tributyltin and tributyltin oxide are still used on boats and ships to prevent growth of barnacles. They are extremely toxic for many invertebrates in the sea, notably some snails whose sexual organs develop abnormally. In these snails the female develops a penis. In oysters and other bivalves, their shells become too thick. Tributyltin must be regarded as one of the most serious environmental pollutants, but contrary to the lower analogues, trimethyl tin and triethyltin, they are not very toxic to man and other mammals. Trimethyltin is of considerable interest for neurotoxicologists because it leads specifically to atrophy of the center for short-term memory, the hippocampus. The ethyl analogue has other serious detrimental effects on the brain. 

AD is characterized by marked atrophy of the cerebral cortex and loss of cortical and subcortical neurons. The pathological hallmarks of AD are senile plaques, which are spherical accumulations of the protein -amyloid accompanied by degenerating neuronal processes, and abundant neurofibrillary tangles, composed of paired helical filaments and other proteins. In advanced AD, senile plaques and neurofibrillary tangles are most abundant in the hippocampus and associative regions of the cortex, whereas areas such as the visual and motor cortices are relatively spared. This corresponds to the clinical features of marked impairment of memory and abstract reasoning, with preservation of vision and movement. 

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