Application of the Co-culture Membrane System Pointed to a Protective Role of Catestatin on Hippocampal Plus Hypothalamic Neurons Exposed to Oxygen and Glucose Deprivation.

Abstract:

:Depletion of oxygen and glucose even for brief periods is sufficient to cause cerebral ischemia, which is a predominant worldwide cause of motor deficits with the reduction of life quality and subsequently death. Hence, more insights regarding protective measures against ischemic events are becoming a major research goal. Among the many neuronal factors, N-methyl-D-aspartate receptors (NMDAR), orexinergic neuroreceptors (ORXR), and sympatho-inhibitory neuropeptide catestatin (CST) are widely involved with ischemic episodes. In this study, it was possible to induce in vitro ischemic conditions of the hamster (Mesocricetus auratus) hippocampal and hypothalamic neuronal cultures, grown on a newly compartmentalized membrane system, via oxygen and glucose deprivation (OGD). These cultures displayed notably differentiated NMDARergic and ORXergic receptor expression activities along with evident brain-derived neurotrophic factor (BDNF) plus orexin A (ORX-A) secretion, especially under co-cultured conditions. Interestingly, addition of CST in OGD-insulted hippocampal cells accounted for upregulated GluN1 and ORX1R transcripts that in the case of the latter neuroreceptor was very strongly (p < 0.001) increased when co-cultured with hypothalamic cells. Similarly, hypothalamic neurons supplied very evident upregulations of GluN1, ORX1R, and above all of GluN2A transcripts along with increased BDNF and ORX-A secretion in the presence of hippocampal cells. Overall, the preferential CST effects on BDNF plus ORX-A production together with altered NMDAR and ORXR levels, especially in co-cultured hypothalamic cells pointed to ORX-containing neurons as major protective constituents against ischemic damages thus opening new scenarios on the cross-talking roles of CST during ischemic disorders.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Mele M,Morelli S,Fazzari G,Avolio E,Alò R,Piscioneri A,De Bartolo L,Facciolo RM,Canonaco M

doi

10.1007/s12035-016-0240-5

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

7369-7381

issue

9

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-016-0240-5

journal_volume

54

pub_type

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