Basal Forebrain Lactate Release and Promotion of Cortical Arousal during Prolonged Waking Is Attenuated in Aging

Abstract

The wake-promoting basal forebrain (BF) is critically involved in sustaining cortical arousal. In the present study, we investigated how aging affects the capacity of the BF to cope with continuous activation during prolonged waking. Increased neuronal activity induces lactate release in the activated brain area, and BF stimulation increases cortical arousal. We used in vivo microdialysis to measure lactate levels in the BF, and electroencephalography (EEG) to measure cortical arousal, during 3 h sleep deprivation (SD) in three age groups of rats. Lactate increased during SD in young but not in aged (middle-aged and old) rats. The increase in high-frequency (HF) EEG theta power (7-9 Hz), a marker of cortical arousal and active waking, was attenuated in the aged. Furthermore, a positive correlation between BF lactate release and HF EEG theta increase was found in young but not in aged rats. We hypothesized that these age-related attenuations result from reduced capacity of the BF to respond to increased neuronal activation. This was tested by stimulating the BF with glutamate receptor agonist NMDA. Whereas BF stimulation increased waking in young and old rats, lactate increase and the HF EEG theta increase were attenuated in the old. Also, the homeostatic increase in sleep intensity after SD was attenuated in aged rats. Our results suggest that an age-related attenuation in BF function reduces cortical arousal during prolonged waking. As the quality of waking is important in regulating the subsequent sleep, reduced cortical arousal during SD may contribute to the age-related reduction in sleep intensity.

Time-of-day modulation of homeostatic and allostatic sleep responses to chronic sleep restriction in rats

“…7A), and two peaks in the delta and theta ranges during wake (Fig. 7B), consistent with previous reports (44,64,65).…”

Sleep, its regulation and possible mechanisms of sleep disturbances

“…Changes in metabolic demand would therefore reflect the homeostatic sleep process with prolonged wakefulness consuming excessively energy. This was demonstrated by studies showing that (i) cortical neurones increase firing in the course of waking ) and (ii) that this increase in cortical activity during waking is paralleled by increases in the brain's lactate level (Urrila et al 2003, Wigren et al 2009, Dash et al 2012. Also, many of the genes involved in energy metabolism and synaptic potentiation are upregulated during waking .…”

“…Whether this reflects reduced build-up of homeostatic sleep pressure with ageing, reduced ability to sleep or problems producing slow waves, is currently not known (Dijk et al 2010). Recent studies suggest, however, that the age-related decrease in SWA is most likely caused by reduced homeostatic sleep pressure (Duffy et al 2009, Wigren et al 2009, Dijk et al 2010, Rytkonen et al 2010, although the underlying molecular mechanisms are not well understood. The reduction could be due to changes in the homeostatic sleep factors (Duffy et al 2009, Rytkonen et al 2010 or due to reduced synaptic density and connectivity (Carrier et al 2011).…”

Spontaneous sleep–wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats

“…Neuronal projections from the basal forebrain regulate the development and functioning of its target regions, including the cortex (Fahnestock et al, 2002;Wigren et al, 2009;Zant et al, 2012). In the cortex, we found that Bdnf transcripts were induced by SD with more prominent changes in Bdnf1 expression: main effect of SD for Bdnf1 F 1,28 = 26.56, P < 0.0001, for Bdnf4 F 1,28 = 10.47, P = 0.003 and a trend for Bdnf9a F 1,28 = 3.29, P = 0.081 (Fig.…”