Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with diverse occurrence and functions. One of the most well-known effects of PACAP is its strong neuroprotective effect. In this presentation we give an insight into recently described neurochemical changes induced by PACAP or altered by PACAP the lack of it. In an invertebrate model for Parkinson’s disease we found that PACAP effectively counteracts the dopamine-decreasing effect of rotenone, a mitochondrial neurotoxin. Similarly, in a 6-hydroxydopamine-induced rat model of Parkinson’s disease, we found that PACAP effectively increases dopamine levels. Furthermore, our proteomics analysis shows that PACAP treatment also counteracts the 6-OHDA-induced decrease in PARK-7 protein, effective against oxidative stress. Studying the role of endogenous PACAP, we found that PACAP-deficient mice show higher susceptibility to toxic agents causing degeneration of the substantia nigra dopaminergic neurons. Using proteomic analysis we revealed that the expression of numerous proteins is altered in the mesencephalon and striatum of knockout mice. Among the altered proteins, several are involved in metabolic processes, energy homeostasis, and structural integrity. ATP-synthase and tubulin beta-2A were expressed more strongly in PACAP-knockout mice. In contrast, the expression of more peptides/proteins markedly decreased in knockout mice, like pyruvate kinase, fructose biphosphate aldolase-A, glutathione S-transferase, peptidyl propyl cis-trans isomerase-A, gamma enolase, beta-synuclein and aspartate amino transferase. The altered expression of these proteins might partially account for the decreased antioxidant, cytoprotective and detoxifying capacity of PACAP-deficient mice. The described changes may provide further explanation for the neuroprotective potency of PACAP.
Highlights
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia
The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression
No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression
Summary
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors
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