In the brain, calcium is thought to play a particular significant role in both health and disease. In normal amounts, calcium apparently triggers signalling pathways essential for certain type of memory; in excess, calcium is thought to cause brain damage. Calcium is intracellular messenger capable of activating many cell functions. Without calcium the nervous system would have no outputs.
Huntington disease is characterized by four features: heritability, behavioral or psychiatric disturbance, cognitive impairment and death -- 15 or 20 years after onset. The disease is caused by widespread loss of neurons in the brain. The mechanism of cell death occurs primarily by the persistent action of glutamate on the N-methyl-D-aspartate, or NMDA, type of glutamate receptors and the excessive influx of calcium. Excess calcium has several damaging consequences that lead to cytotoxicity and death. First, it can activate calcium dependent proteases that produce a toxic effect on nerve cells. Second, calcium produces eicosanoids that produce inflammation and free radicals that cause tissue damage.
Brain damage from repeated seizures can occur with the preferential loss of neurons in the hippocampus region of the brain. The release of excitatory amino acid transmitter, L-glutamate, causes overactivation of glutamate receptors. This leads to an excessive increase in intracellular calcium, which activates many calcium-dependent enzymes, such as calcenurin, calpains and lipases. A study published in 2003 and conducted at the University of Wisconsin, found that calcium-dependent enzymes cause production of free radicals that damage vital cellular protein and leads to brain damage.
Spinocerebellar ataxia, or SCA3 is a fatal genetic disorder that impairs coordination, speech, and vision. A 2008 study published in the Journal of Neuroscience found that the cells from a person with spinocerebellar ataxia 3 showed abnormally high levels of calcium release when treated with bradykinin, a substance which activates the calcium channel present in the brain. Such abnormal calcium release results in impaired motor functions in people with SCA3.
Dyskinesias is characterized by excessive motor activity, the symptoms of which are involuntary movements like tremors and writhing. The involuntary movements result from the deposition of excess calcium in the basal ganglia and cerebellum regions of the brain.
- PubMed: “Medical Hypotheses”; Targeting Glutamate Mediated Excitotoxicity in Huntington's Disease: neural progenitors and partial glutamate antagonist—memantine; M. Anitha; Jan 2011
- PubMed: “Epilepsy Currents”; Radical Ideas About Seizure-Induced Neuronal Damage; Carl E. Stafstrom; March 2003.
- PubMed: “Biological Psychiatry”; Antagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-dihydroxyphenylalanine-induced Dyskinesia; Schuster S; March 2009
- Medical News Today: Deranged Calcium Signalling Contributes To Neurological Disorder