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Impaired calcium regulation in subcortical vascular encephalopathy
1Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Insights
Lymphocyte calcium signaling is impaired in patients with subcortical vascular encephalopathy (SVE), indicating potential immune dysfunction. This immune dysregulation may offer new insights into SVE pathogenesis and inflammatory processes.
Area of Science:
- Neuroimmunology
- Cellular Physiology
Background:
- Chronic cerebral ischemia may affect immune status, including T lymphocyte proliferation.
- Progressive subcortical vascular encephalopathy (SVE) is a condition where immune function changes may occur.
Purpose of the Study:
- To investigate intracellular calcium ([Ca2+]i) homeostasis in lymphocytes of SVE patients.
- To compare calcium regulation in lymphocytes from SVE patients versus Alzheimer's disease (AD) patients.
Main Methods:
- Measured basal and phytohemagglutinin (PHA)-stimulated [Ca2+]i in lymphocytes from 26 SVE patients, 26 AD patients, and 26 controls using the fura 2 method.
- Assessed the impact of beta-amyloid peptide and tetraethylammonium on Ca2+ signaling.
Main Results:
- Lymphocytes from SVE patients showed a significantly reduced Ca2+ response after PHA stimulation compared to controls and AD patients.
- Beta-amyloid affected Ca2+ signaling similarly in SVE and control lymphocytes but reduced it in AD lymphocytes.
- Potassium channels were not implicated in the impaired Ca2+ response in SVE lymphocytes.
Conclusions:
- Lymphocyte calcium homeostasis appears impaired in SVE, suggesting a role for immune disturbances in the disease's pathogenesis.
- These findings may provide new insights into the inflammatory or immunologic aspects of SVE.
Background And Purpose:
A number of clinical observations and first in vitro findings indicate that chronic cerebral ischemia influences immunologic status, such as the proliferative response of T lymphocytes. The purpose of the present report was to assess (1) whether changes of immune function are likewise detectable in patients with progressive subcortical vascular encephalopathy (SVE) by investigating the [Ca2+]i homeostasis of lymphocytes and (2) whether differences exist in calcium regulation between lymphocytes from SVE patients and from Alzheimer's disease (AD) patients. This is of great interest, since specific changes have been reported recently in AD patients.
Methods:
[Ca2+]i was recorded in 26 patients with SVE, 26 age-matched nondemented control subjects, and 26 age-matched patients with AD. Basal [Ca2+]i and [Ca2+]i after lymphocyte activation with the mitogen phytohemagglutinin (PHA) were measured with the fura 2 method. In addition, modulation of the Ca2+ signaling by the peptide beta-amyloid and the potassium channel blocker tetraethylammonium was studied.
Results:
Basal [Ca2+]i was not different between patients and control subjects. After stimulation with PHA, however, a significant reduction of the Ca2+ response could be observed in lymphocytes of SVE patients compared with control subjects and with AD patients, providing evidence that the Ca2+ homeostasis of lymphocytes is impaired in SVE. The effect of the peptide beta-amyloid, the major constituent of senile plaques in AD brain, on Ca2+ signaling was similar in SVE patients and nondemented control subjects but typically reduced in cells of AD patients. Potassium channels were not involved in the impaired Ca2+ response of SVE lymphocytes after cell activation.
Conclusions:
[Ca2+]i is not only one of the most important second messengers in signal transduction of many cells but also an early event in the signal cascade of cell proliferation as a reaction to antigen recognition. This mechanism seems to be impaired in SVE. These findings may result in new insights regarding the pathogenesis of this disease and the possible involvement of inflammatory or immunologic disturbances.