Age-related alterations of GABAergic input to CA1 Pyramidal neurons and its control by nicotinic acetylcholine receptors in rat hippocampus

Old-onset caloric restriction effects on neuropeptide Y- and somatostatin-containing neurons and on cholinergic varicosities in the rat hippocampal formation

“…We have found that aging induced a significant decrease of the density of cholinergic varicosities in the dentate hilus and also in the CA3 and CA1 subfields of the HF, in accordance with other works that described aging deleterious effects upon the cholinergic system in several brain regions (Zhang et al 1998;Lukoyanov et al 1999;Cardoso et al 2006;Potier et al 2006;Ypsilanti et al 2008). Interestingly, we have also found that old-onset caloric-restricted rats presented a higher density of cholinergic varicosities in the dentate hilus and in the CA3 and CA1 hippocampal subfields when compared to age-matched 24-month-old controls.…”

“…Furthermore, we have also found, in the same hippocampal regions, that aging induced significant reduction of the total number of SS-IR neurons. This finding was as well described by others that found reduction not only in the hippocampal SS-IR neuronal number (Spiegel et al 2013) and density (Potier et al 2006;Gavilán et al 2007;Stanley et al 2012) but also in its mRNA levels (Vela et al 2003;Gavilán et al 2007). The reduction of NPY-IR and SS-IR neurons during aging could be due to several reasons including cell death, decrease of activity, or even alteration of the protein conformation (Cadacio et al 2003;Vela et al 2003;Gavilán et al 2007).…”

“…Bearing in mind that NPY-and SS-ergic systems are dependent of the cholinergic innervation in the cerebral cortex (Milner et al 1997;Zhang et al 1998;Cardoso et al 2006;Potier et al 2006), we also sought to analyze the effects of aging and caloric restriction upon the cholinergic system of the HF. We have found that aging induced a significant decrease of the density of cholinergic varicosities in the dentate hilus and also in the CA3 and CA1 subfields of the HF, in accordance with other works that described aging deleterious effects upon the cholinergic system in several brain regions (Zhang et al 1998;Lukoyanov et al 1999;Cardoso et al 2006;Potier et al 2006;Ypsilanti et al 2008).…”

“…Increasing evidence suggests that acethylcholine exerts trophic effects upon target areas of the basal forebrain cholinergic projections, including the cerebral cortex (Wettstein et al 1995;Zhu and Waite 1998;Cardoso et al 2006). It has been described that NPY-IR and SS-IR neurons are innervated by cholinergic terminals (Lamour and Epelbaum 1988;Wettstein et al 1995;Jolkkonen et al 1997;Potier et al 2006) and that the selective lesion of basal forebrain cholinergic nucleus decreases the number of cortical NPY-and SS-IR neurons (Jolkkonen et al 1997;Milner et al 1997;Zhang et al 1998). Furthermore, we have previously reported that infusion of the neurotrophin NGF, known to have neurotrophic effect upon cholinergic neurons (Cuello et al 1992;Niewiadomska et al 2002), resulted in the recovery of VAChT cholinergic varicosities in the somatosensory cortex of old rats that was paralleled by a complete recovery of expression of NPY in the same region (Cardoso et al 2006).…”

“…Furthermore, knowing that in the cortex, the NPYand SS-ergic systems seem to be dependent of cholinergic system (Jolkkonen et al 1997;Zhang et al 1998;Cardoso et al 2006;Potier et al 2006), we also studied the effects of caloric restriction upon the cholinergic fibers by analyzing the vesicular acetylcholine transporter (VAChT) immunoreactive (IR) varicosities density. Finally, because humans have difficulties engaging in caloric restriction regimen over the long-term (Scheen 2008;Anton and Leeuwenburgh 2013), we decided to start the nutritional deprivation at 18-month-old rats (oldonset) and to verify if the chronic treatment starting at this age is enough to induce the expected beneficial effects.…”