Abstract
It is known that aging is frequently accompanied by a decline in cognition. Furthermore, aging is associated with lower serum IGF-I levels that may contribute to this deterioration. We studied the effect of IGF-I in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging. Local injection of IGF-I in the HDB nucleus increased their neuronal activity and induced fast oscillatory activity in the electrocorticogram (ECoG). Furthermore, IGF-I facilitated tactile responses in the primary somatosensory cortex elicited by air-puffs delivered in the whiskers. These excitatory effects decreased in old mice. Immunohistochemistry showed that cholinergic HDB neurons express IGF-I receptors and that IGF-I injection increased the expression of c-fos in young, but not in old animals. IGF-I increased the activity of optogenetically-identified cholinergic neurons in young animals, suggesting that most of the IGF-I-induced excitatory effects were mediated by activation of these neurons. Effects of aging were partially ameliorated by chronic IGF-I treatment in old mice. The present findings suggest that reduced IGF-I activity in old animals participates in age-associated changes in cortical activity.
Highlights
Aging is a physiological process accompanied by a decline in cognitive performance
We studied the effect of insulin-like growth factor-I (IGF-I) in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging
Aging is associated with a reduction in the GH-IGF-I axis activity, resulting in lower serum IGF-I levels (Breese et al, 1991) and impaired brain IGF-I activity (Muller et al, 2012)
Summary
Aging is a physiological process accompanied by a decline in cognitive performance. In humans, aging has been associated with numerous and diverse changes in the EEG and on sleep, such as increased sleep fragmentation, decreased total sleep time, sleep efficiency, and in the frequency bands of the EEG (Landolt et al, 1996; Luca et al, 2015; Mander et al, 2017). Numerous studies have provided important insights into the global age-dependent alterations in sleep-wake and EEG architecture in mice (Hasan et al, 2012; Panagiotou et al, 2017; McKillop et al, 2018). There are notable discrepancies between species concerning the effects of aging. Slow-wave sleep (SWS) is decreased in aged humans, whereas it is enhanced in aged mice (Panagiotou et al, 2017; McKillop et al, 2018).
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