Abstract
Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood–brain barrier, which triggers gliosis after ischemic insults.
Highlights
Intermittent fasting (IF) entails alternate cycles of feeding and fasting to induce energy and dietary restriction [1]
The three major mechanisms underlying the neuronal death induced by transient global brain or forebrain ischemia include the following: (1) oxidative stress induced by overproduction of reactive oxygen species (ROS), (2) inflammatory response by pro-inflammatory cytokines and immune cells, and (3) glutamate-induced excitotoxicity [25,26,27]
We investigated whether an IF-mediated increase in CB expression influenced neuronal survival, reactive gliosis and blood–brain barrier (BBB) leakage in the hippocampal cornu ammonis 1 (CA1) region
Summary
Intermittent fasting (IF) entails alternate cycles of feeding and fasting to induce energy and dietary restriction [1]. A few studies using rodent models of focal cerebral ischemia have demonstrated that IF increases resistance to ischemia/reperfusion injury in rodent brains [1,2,3,4]. In these studies, IF attenuates tissue damage (infarction) and neurological deficit following focal brain ischemia, demonstrating that IF acts as a mild metabolic stressor in neurons or glial cells and effectively upregulates the expression of several neuroprotective antioxidant enzymes, inflammatory mediators, and calcium-binding proteins. Irreversible neuronal death in the gerbil model occurs in vulnerable subregions of the brain, including the striatum, neocortex and hippocampus [6,7]. Gliosis in CNS insults is initiated after the disruption of the blood–brain barrier (BBB), allowing non-CNS molecules including blood and serum components to enter the brain parenchyma [11,12,13,14]
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