Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals

Abstract

Aging leads to progressive deterioration of physiological function and diminished responses to environmental stress. Organic and functional alterations are frequently observed in elderly subjects. Although chronic sleep loss is observed during senescence, little is known about the impact of insufficient sleep on cellular function in aging neurons. Disruption of neuronal calcium (Ca²⁺) signaling is related to impaired neuronal function and cell death. It has been hypothesized that sleep deprivation may compromise neuronal stability and induce cell death in young neurons; however, it is necessary to evaluate the impact of aging on this process. Therefore, the aim of this study was to evaluate the effects of chronic sleep restriction (CSR) on Ca²⁺ signaling and cell death in the hippocampus of young and aged animals. We found that glutamate and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) induced a greater elevation in cytosolic Ca²⁺ ([Ca²⁺](c)) in hippocampal slices from aged rats subjected to CSR compared to age-matched controls. Interestingly, aged-matched controls showed a reduced Ca²⁺ response to glutamate and FCCP, relative to both CSR and control young animals. Apoptotic nuclei were observed in aged rats from both treatment groups; however, the profile of apoptotic nuclei in aged CSR rats was highly variable. Bax and Bcl-2 protein expression did not change with aging in the CSR groups. Our study indicates that aging promotes changes in Ca²⁺ signaling, which may also be affected by CSR. These age-dependent changes in Ca²⁺ signaling may increase cellular vulnerability during CSR and contribute to Ca²⁺ signaling dysregulation, which may ultimately induce cell death.

The Regulation of SKF38393 on the Dopamine and D1 Receptor Expression in Hippocampus during Chronic REM Sleep Restriction

“…In addition, after CSR, the expression of D 1 R at transcriptional and translational level was significantly reduced in CSR group while increased in SKF group (Figure 2C-E).Our findings demonstrate that although SKF38393 administration during the late phase of CSR cannot change the loss of weight and stamina, it may partially improve the deficiency of spatial learning and memory induced by CSR and enhance the explorative activity. At the same time, it can also protect the hippocampal ultrastructure and the function of dopaminergic system in hippocampus during the late phase of CSR.CSR cannot only decrease hippocampal volume but also induce apoptosis and calcium overload in the hippocampus of rats [7,8]. The present study further demonstrates that CSR can lead to the destruction of the hippocampal neuronal ultrastructure, including Figure 2 Results of morphological and biochemical determination.…”

Measures of Sleep–Wake Patterns and Risk of Mild Cognitive Impairment or Dementia in Older Women

“…(39) In addition, in aged rats, chronic sleep restriction leads to alterations in Ca++ signaling and abnormalities of synaptic plasticity in the hippocampus, an area of the brain that plays an important role in memory and where early abnormalities are seen in Alzheimer's disease. (40-42) Recent studies in humans have linked lower sleep efficiency and greater WASO measured by actigraphy as well as poorer sleep quality and shorter sleep duration measured by self-report to greater amyloid deposition. (43,44)…”

Sleep and Human Aging

“…Functionally, chronic sleep restriction in rats, which is more representative of age-related sleep impairment than acute total sleep deprivation, adds to age-related calcium signaling impairments within the hippocampus of older animals (de Souza et al, 2012). This represents another viable route through which impairments in hippocampal-dependent learning can be affected by sleep impairments in later life.…”