Effect of Hormone Replacement Therapy in Normalizing Age Related Neuronal Markers in Different Age Groups of Naturally Menopausal Rats

Abstract

Aging of the normal brain is accompanied by changes in its structure, function, and metabolism. There are significant gender differences in aging brain. Most of these changes increase during menopausal condition in females when the level of estradiol and progesterone are decreased. The objective of this study was to determine the effect of estradiol and progesterone (separate as well as combined) hormones in neuronal tissues from naturally menopausal rats of different age groups. Results show decreased activity of Acetylcholine esterase (AChE) whereas the level of lipid peroxidation increased with age, and after the hormone treatments both AChE activity and level of lipid peroxidation returned to control values. The deposition of lipofuscin, a pigment that accumulated intraneuronally in brain and other tissues and is considered a marker of aging, was increased with aging and the hormone treatment decreased this deposition. The present study clearly shows reduction in risk factors associated with aging in the murine model system by hormone treatments, namely estrogen and progesterone by increasing the activity of acetylcholine esterase and decreasing the levels of lipid peroxidation and lipofuscin deposition in different parts of aging brain. This study suggests that hormone replacement therapy may either reduce or delay the onset of age related diseases like Alzheimer's, Parkinson's and other neurological disorders.

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions

“…Earlier studies have revealed that there is an increase in the lipid peroxides of aged liver and brain homogenates (Miyazawa et al 1993). Lipid peroxide levels were found to be significantly higher in brains of 18 months old as compared to 4 months old rats (Noda et al 1982;Moorthy et al 2005).…”

“…The accumulation of lipofuscin in cells occurs because it is undegradable and cannot be removed from the cells via exocytosis. As age progresses, the lipofuscin content per neuron as well as the number of pigmented neurons has been shown to increase in a linear fashion in many regions of the brain (Sharma et al 1993;Drach et al 1994;Moorthy et al 2005). Intraneuronal accumulation of lipofuscin is considered to be a marker of neuronal aging, and its formation appears to be integrative and proportional to the occurrence of lipid peroxidation.…”

A metabolic and functional overview of brain aging linked to neurological disorders

“…Percentage changes in the activities of NADP linked, glycolytic and membrane associated enzymes from synaptosomes prepared from cerebral hemispheres of aging rat brain taking 20 days old as 100%. Figure derived from Baquer et al (1990) Earlier work and ample evidence has shown that peroxidative damage to lipid and protein occurs with the aging process and the products of these reactions accumulate in the brain with age (Bondereff 1964;Mann and Yates 1974;Davison and Wright 1980;Baquer et al 1990;Moorthy et al 2004aMoorthy et al , 2005aBala et al 2006;Sinha et al 2005Sinha et al , 2008.…”

“…K ? ATPase Moorthy et al 2004aMoorthy et al , 2005aSiddiqui et al 2005) both enzymes controlling the polarization of neurons.…”

“…For example, by dietary regime or hormonal administration to aging animals to suppress formation of free radicals. Moorthy et al (2005a) have shown that administration of estradiol and progesterone reverse some of the aging effects in older animals. Mantha et al (2006) had shown the changes in membrane fluidity in synaptosomes with age.…”