Altered function of neuronal L-type calcium channels in ageing and neuroinflammation: Implications in age-related synaptic dysfunction and cognitive decline

The rapid developments in science have led to an increase in human life expectancy and thus, ageing and age-related disorders/diseases have become one of the greatest concerns in the 21st century. Cognitive abilities tend to decline as we get older. This age-related cognitive decline is mainly attributed to aberrant changes in synaptic plasticity and neuronal connections. Recent studies show that alterations in Ca2+ homeostasis underlie the increased vulnerability of neurons to age-related processes like cognitive decline and synaptic dysfunctions. Dysregulation of Ca2+ can lead to dramatic changes in neuronal functions. We discuss in this review, the recent advances on the potential role of dysregulated Ca2+ homeostasis through altered function of L-type voltage gated Ca2+ channels (LTCC) in ageing, with an emphasis on cognitive decline. This review therefore focuses on age-related changes mainly in the hippocampus, and with mention of other brain areas, that are important for learning and memory. This review also highlights age-related memory deficits via synaptic alterations and neuroinflammation. An understanding of these mechanisms will help us formulate strategies to reverse or ameliorate age-related disorders like cognitive decline.