Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion.

This indicates that decrease of NE in locus ceruleus projection areas facilitates the inflammatory reaction of microglial cells in AD and impairs microglial migration and phagocytosis, thereby contributing to reduced Abeta clearance. Supplying the mice the norepinephrine precursor L-threo-DOPS restored microglial functions in NE-depleted mice. In vivo laser microscopy confirmed a reduced recruitment of microglia to Abeta plaque sites and impaired microglial Abeta phagocytosis in NE-depleted APP-transgenic mice. Induced degeneration of the locus ceruleus increased expression of inflammatory mediators in APP-transgenic mice and resulted in elevated Abeta deposition. NE stimulation of mouse microglia suppressed Abeta-induced cytokine and chemokine production and increased microglial migration and phagocytosis of Abeta. To elucidate the effect of LC degeneration and subsequent NE deficiency on Alzheimer's disease pathology, we evaluated NE effects on microglial key functions. Locus ceruleus (LC)-supplied norepinephrine (NE) suppresses neuroinflammation in the brain. It improves cognitive dysfunction and ameliorates cerebral damage. LIR also improves hippocampal histological features of ALC元 administrated rats and decreases the percentage of neuronal loss. LIR prevents the impairment of learning and improves both working memory and reference memory through significant reduction of serum tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ) and malondialdehyde (MDA) and through the increase of superoxide dismutase (SOD), dopamine, adrenaline, and noradrenaline. Histopathological and immunofluorescent examinations were performed.

Serum blood glucose, proinflammatory cytokines, oxidative stress markers were measured and hippocampal tissue homogenate neurotransmitters were evaluated. To explore the probable neuroprotective impact of Glucagon-like peptide-1 (GLP-1) on rats' behavior and to elucidate its underlying mechanisms.Ī total of 24 male albino rats were assigned to control, LIR (300 µg/kg subcutaneously (s.c.)), AD only (100 mg/kg aluminum chloride (AlCl3 ) orally) and LIR + AD treated groups. Liraglutide (LIR) has neuroprotective effects in preclinical animal models. Alzheimer's disease (AD) is a worldwide severe medical and social burden.

Epinephrine deficiency diseases