Ghrelin as a neuroprotective and palliative agent in Alzheimer's and Parkinson's disease.

Ghrelin is a gastric hormone that stimulates growth hormone (GH) secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, GH secretagogue receptor (GHSR1a), which is most highly expressed in the pituitary and hypothalamus. Nowadays there is considerable evidence showing that the GHSR1a is also expressed in numerous extra-hypothalamic neuronal populations and the physiological role of ghrelin is by far wider than considered before including learning and memory, anxiety, depression and neuroprotection. The present review attempts to provide a comprehensive picture of the role of ghrelin in the central nervous system and to highlight recent findings showing its potential as an innovative therapeutic agent in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.

Neuropeptide Y (NPY) prevents depressive-like behavior, spatial memory deficits and oxidative stress following amyloid-ß (Aß(1-40)) administration in mice.

Neuropeptide Y (NPY) is a 36-amino acid peptide widely distributed in the central nervous system (CNS) that has been associated with the modulation of several functions including food intake, learning and memory, mood and neuroprotection. There is great interest in understanding the role of NPY in the deleterious effects induced by the central accumulation of amyloid-ß (Aß) peptides, a pathological hallmark of Alzheimer's disease (AD). Herein, we evaluated the effects of a single intracerebroventricular (i.c.v.) administration of NPY (0.0234 µmol/µL) 15 min prior to the i.c.v. injection of aggregated Aß1-40 peptide (400 pmol/mouse) in behavioral and neurochemical parameters related to oxidative stress in mice. Pretreatment with NPY prevented Aß1-40-induced depressive-like responses and spatial memory impairments evaluated in the tail suspension and object location tasks, respectively. The protective effects of NPY on spatial memory of Aß1-40-treated mice were abolished by the pretreatment with the selective Y2 receptor antagonist BIIE0246. On the other hand, the administration of NPY and Aß1-40 did not alter the performance of the animals in the elevated plus-maze and open field arena, indicating lack of effects on anxiety state and locomotor function. Although Aß1-40 infusion did not change hippocampal and cortical glutathione peroxidase (GPx) activity and glutathione (GSH) levels, Aß1-40-infused animals showed an increased lipid peroxidation in hippocampus and prefrontal cortex that were blunted by NPY administration. These findings indicate that central administration of NPY prevents Aß1-40-induced depressive-like behavior and spatial memory deficits in mice and that this response is mediated, at least in part, by the activation of Y2 receptors and prevention of oxidative stress.