Leptin and its role in hippocampal synaptic plasticity

Abstract

It is well documented that the hormone leptin plays a pivotal role in regulating food intake and body weight via its hypothalamic actions. However, leptin receptors are expressed throughout the brain with high levels found in the hippocampus. Evidence is accumulating that leptin has widespread actions on CNS function and in particular learning and memory. Recent studies have demonstrated that leptin-deficient or-insensitive rodents have impairments in hippocampal synaptic plasticity and in spatial memory tasks performed in the Morris water maze. Moreover, direct administration of leptin into the brain facilitates hippocampal long-term potentiation (LTP), and improves memory performance in mice. There is also evidence that, at the cellular level, leptin has the capacity to convert hippocampal short-term potentiation (STP) into LTP, via enhancing NMDA receptor function. Recent data indicates that leptin can also induce a novel form of NMDA receptor-dependent hippocampal long-term depression. Here, we review the evidence implicating a key role for the hormone leptin in modulating hippocampal synaptic plasticity and discuss the role of lipid signaling cascades in this process.

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

“…Moreover, direct administration of leptin into the dentate gyrus enhances LTP in rats (Wayner et al, 2004), while direct leptin administration into the CA1 region of the hippocampus improves spatial memory and learning in mice (Farr et al, 2006). At the cellular level, leptin has been shown to enhance NMDA receptor function (Shanley et al, 2001), possibly through rapid trafficking of NMDA receptors to the plasma membrane (Harvey et al, 2006), in a manner analogous to insulin (Skeberdis et al, 2001). Thus leptin may enhance memory and learning through mechanisms that modulate synaptic plasticity in the hippocampus.…”

Central leptin insufficiency syndrome: An interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions

“…Intriguingly, leptin insufficiency in the brain of obese and diabetic patients, may also adversely impact neural functions [2,38,49,50,58,60]. Diabetes mellitus was associated with cognitive deficits, including psychomotor efficiency, attention, learning and memory, intelligence and executive function.…”

“…Diabetes mellitus was associated with cognitive deficits, including psychomotor efficiency, attention, learning and memory, intelligence and executive function. Moreover, even non-diabetic individuals suffering either from hyperinsulinemia and insulin resistance or from poor glucose regulation, displayed impaired learning and memory performance, and atrophy of temporal lobe structures, including hippocampus and amygdala [49,50,56,60,107,113]. Thus, a chronic low-grade decrease in central leptin levels in humans, a consequence of impaired BBB transport [12,27,29,124], may inflict hippocampal damage, volume loss and atrophy, decrease general cognition performance, and memory impairment.…”

“…Leptin injections reinstated myelinization, synaptogenesis, and promoted overall brain growth in ob/ob mice [1,16,23,24,60,100,117,128]. Also, the possibility that cognition deficit may be associated with leptin insufficiency has been explored.…”

“…Consequently, as alluded to earlier, it is highly possible that when leptin transport into the CNS is compromised in obese and aging subjects, and those suffering from metabolic diseases, low levels of leptin in the hippocampus may instill cognitive deterioration [56,60,113]. Leptin insufficiency in the brain either alone, or in concert with hyperglycemia and/or hyperinsulinemia is a significant risk factor for impaired cognitive function in the aging population [56,60,113].…”