Joseph M. Thompson and Dr. Edwin D. Lephart, Zoology

Calcium plays a major role in the body; it’s involved in bone growth, muscle contraction, and especially in the central nervous system (CNS) development and function. However, an overabundance of calcium leads to cell degeneration and eventually cell death, disrupting the formation of synapses. The body regulates excess calcium in the brain through calcium-binding proteins.

Calbindin-28k (CALB) is a calcium-binding protein that serves an important role in the development and function of the CNS [1,2]. CALB is the most abundant calcium-binding protein in neurons, acting to buffer intracellular calcium levels for proper function. Brain sites that are exposed to toxic amounts of calcium where calcium-binding proteins are present experience less neurodegeneration than areas where the proteins are less abundant [3]. These proteins sequester and regulate intracellular calcium during genesis of CNS and act as neuroprotective factors against apoptosis (programmed cell death) that is associated with neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s disease [2].

Phytoestrogens (estrogen-like molecules) are plant hormones that resemble and mimic the actions and effects of steroidal estrogens that occur naturally in the body. High concentrations of phytoestrogens are thought to reduce the risk of breast cancer, prostate cancer, coronary heart disease, and osteoporosis. Phytoestrogens may also have adverse effects. Our lab has previously published that dietary phytoestrogens can significantly decrease CALB levels in adult male rat brains [4,5].

In the female body, the hormones estradiol and progesterone fluctuate regularly through four different phases. It is not known how the fluctuation of these hormones during the female estrous cycle effects the calcium binding proteins in the brain. My project has focused on quantifying and qualifying CALB levels in order to see how the natural circulating estrogen levels effect the calcium-binding protein.

I observed the CALB levels in different parts of the brain using Western Blot Analysis. The results of my research show there to be a significant increase of CALB levels in brain tissue in which the rats were sacrificed 24 hours after the estrous phase of the cycle, while the other stages in the cycle showed no significant deviation from one another. These results lead to the conclusion that CALB levels do fluctuate during the estrous cycle in female rats.

These results are very significant considering that while much attention has been devoted to the effects of testosterone on calbindin levels, little was known about the effects of estrogen before this project. Gaining a greater understanding of why and when calcium-binding proteins fluctuate will hopefully help us to better understand Alzheimer’s, Huntington’s, and Parkinson’s diseases in females.

This research has been written up in an abstract to be published in the near future in a scientific journal.

References

1. Baimbridge KG, Celio MR. Roger JH, Calcium-binding proteins in the nervous system. Trends Neuroscience 15 (1992) 303-308
2. Iacopino AM, Quintero EM, Miller EK, Calbindin-D28k a potential neuroprotective protein. Neurodegeneration 3 (1994) 1-20
3. Hirsch EC, Mouat A, Thomasset M, Javoy-Agid F, Graybiel AM, Expression of calbindin- D28K-like immunoreactivity in catecholaminergic cell groups of the human midbrain: Normal distribution and distribution in Parkinson’s disease. Neurodegeneration 1 (1992) 83- 93
4. Lephart ED, Dimorphic expression of calbindin-D28K in the medial basal hypothalamus from perinatal male and female rats. Developmental Brain Research 9 (1996) 281-284
5. Lephart ED, Watson MA, Jacobsen NA, Rhees RW, Ladle DR, Developmental Brain Research 100 (1997) 117-120.