Essential Role of Astrocytes in Learning and Memory.

One of the most biologically relevant functions of astrocytes within the CNS is the regulation of synaptic transmission, i.e., the physiological basis for information transmission between neurons. Changes in the strength of synaptic connections are indeed thought to be the cellular basis of learning and memory. Importantly, astrocytes have been demonstrated to tightly regulate these processes via the release of several gliotransmitters linked to astrocytic calcium activity as well as astrocyte-neuron metabolic coupling. Therefore, astrocytes seem to be integrators of and actors upon learning- and memory-relevant information. In this review, we focus on the role of astrocytes in learning and memory processes. We delineate the recognized inputs and outputs of astrocytes and explore the influence of manipulating astrocytes on behaviour across diverse learning paradigms. We conclude that astrocytes influence learning and memory in various manners. Appropriate astrocytic Ca2+ dynamics are being increasingly identified as central contributors to memory formation and retrieval. In addition, astrocytes regulate brain rhythms essential for cognition, and astrocyte-neuron metabolic cooperation is required for memory consolidation.

JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

c-Jun N-terminal kinases (JNKs) are a family of protein kinases activated by a myriad of stimuli consequently modulating a vast range of biological processes. In human postmortem brain samples affected with Alzheimer's disease (AD), JNK overactivation has been described; however, its role in AD onset and progression is still under debate. One of the earliest affected areas in the pathology is the entorhinal cortex (EC). Noteworthy, the deterioration of the projection from EC to hippocampus (Hp) point toward the idea that the connection between EC and Hp is lost in AD. Thus, the main objective of the present work is to address if JNK3 overexpression in the EC could impact on the hippocampus, inducing cognitive deficits. Data obtained in the present work suggest that JNK3 overexpression in the EC influences the Hp leading to cognitive impairment. Moreover, proinflammatory cytokine expression and Tau immunoreactivity were increased both in the EC and in the Hp. Therefore, activation of inflammatory signaling and induction of Tau aberrant misfolding caused by JNK3 could be responsible for the observed cognitive impairment. Altogether, JNK3 overexpression in the EC may impact on the Hp inducing cognitive dysfunction and underlie the alterations observed in AD.

Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: A Focus on Insulin Resistance.

Alzheimer's disease (AD) is the main type of dementia and is a disease with a profound socioeconomic burden due to the lack of effective treatment. In addition to genetics and environmental factors, AD is highly associated with metabolic syndrome, defined as the combination of hypertension, hyperlipidemia, obesity and type 2 diabetes mellitus (T2DM). Among these risk factors, the connection between AD and T2DM has been deeply studied. It has been suggested that the mechanism linking both conditions is insulin resistance. Insulin is an important hormone that regulates not only peripheral energy homeostasis but also brain functions, such as cognition. Insulin desensitization, therefore, could impact normal brain function increasing the risk of developing neurodegenerative disorders in later life. Paradoxically, it has been demonstrated that decreased neuronal insulin signalling can also have a protective role in aging and protein-aggregation-associated diseases, as is the case in AD. This controversy is fed by studies focused on neuronal insulin signalling. However, the role of insulin action on other brain cell types, such as astrocytes, is still unexplored. Therefore, it is worthwhile exploring the involvement of the astrocytic insulin receptor in cognition, as well as in the onset and/or development of AD.