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Abstract Through their well described actions in the hypothalamus, appetitive peptides such as insulin, orexin and leptin are recognized as important regulators of food intake, body weight and body composition. Beyond these metabolic activities, these peptides also are critically involved in a wide variety of activities ranging from modulation of immune and neuroendocrine function to addictive behaviors and reproduction.

The neurological activities of insulin, orexin and leptin also include facilitation of hippocampal synaptic plasticity and enhancement of cognitive performance. In view of the importance of these peptides in metabolic disorders, it is not surprising that there is a greater focus on their potential role in cognitive deficits associated with aging.

The goal of this review is to describe the evidence from clinical and pre-clinical studies implicating insulin, orexin and leptin in the etiology and progression of age-related cognitive decline.

Collectively, these studies support the hypothesis that leptin and insulin resistance, concepts normally associated with the hypothalamus, are also applicable to the hippocampus. Introduction Neuroplasticity may be defined as the ability of an organism to adapt to changes in the external or internal milieu and can be assessed using a variety of experimental approaches.

In this regard, neuroplasticity can be evaluated through approaches ranging from neuroanatomical analyses to neurochemical and electrophysiological measures to behavior.

An important question is what are the underlying molecular, cellular and neurochemical factors that regulate brain plasticity? In addition to neurotransmitters and neurotrophic factors, insulin, leptin and orexin are examples of neuropeptides that promote hippocampal synaptic plasticity Figure 1. Insulin derived from the pancreas and leptin derived from adipocytes have well described activities in the hypothalamus, which includes regulation of the orexin system. Indeed, recent studies indicate that activation of these orexigenic pathways facilitates the performance of hippocampal-dependent tasks Stanley et al.

Conversely, age-related decline in hippocampal neuroplasticity and cognition is associated with impairments in the functional activities of insulin, orexin and leptin. The focus of this review is to highlight how these peptides that are normally associated with the regulation of metabolism and body weight play a critical role in the facilitation of hippocampal neuronal plasticity, as well as how the impairments in the neuroplasticity activities of these appetitive peptides is a contributing factor in age-related cognitive decline.

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FOOD FOR THOUGHT: THE ROLE OF APPETITIVE PEPTIDES IN AGE-RELATED COGNITIVE DECLINE

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