miRNA-132/212 Gene-Deletion Aggravates the Effect of Oxygen-Glucose Deprivation on Synaptic Functions in the Female Mouse Hippocampus

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 7; p. 1709
• Main Authors: Bormann, Daniel, Stojanovic, Tamara, Cicvaric, Ana, Schuld, Gabor J., Cabatic, Maureen, Ankersmit, Hendrik Jan, Monje, Francisco J.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 06.07.2021; MDPI
• Subjects: Acetylcholine receptors (muscarinic); Acetylcholine receptors (nicotinic); Alzheimer's disease; Animal cognition; Brain research; Brain slice preparation; Complications; Dentate gyrus; field excitatory postsynaptic potentials (fEPSP); Gene deletion; Glucose; Hippocampus; Hypoxia; Injuries; Ischemia; MeCP2 protein; Memory; Methyl-CpG binding protein; miRNA; miRNA 132/212; Neurogenesis; Oxygen; oxygen-glucose deprivation (OGD); Pathophysiology; Physiology; Stroke; Synaptic transmission; United Kingdom > UK; Austria
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10071709

Cerebral ischemia and its sequelae, which include memory impairment, constitute a leading cause of disability worldwide. Micro-RNAs (miRNA) are evolutionarily conserved short-length/noncoding RNA molecules recently implicated in adaptive/maladaptive neuronal responses to ischemia. Previous research independently implicated the miRNA-132/212 cluster in cholinergic signaling and synaptic transmission, and in adaptive/protective mechanisms of neuronal responses to hypoxia. However, the putative role of miRNA-132/212 in the response of synaptic transmission to ischemia remained unexplored. Using hippocampal slices from female miRNA-132/212 double-knockout mice in an established electrophysiological model of ischemia, we here describe that miRNA-132/212 gene-deletion aggravated the deleterious effect of repeated oxygen-glucose deprivation insults on synaptic transmission in the dentate gyrus, a brain region crucial for learning and memory functions. We also examined the effect of miRNA-132/212 gene-deletion on the expression of key mediators in cholinergic signaling that are implicated in both adaptive responses to ischemia and hippocampal neural signaling. miRNA-132/212 gene-deletion significantly altered hippocampal AChE and mAChR-M1, but not α7-nAChR or MeCP2 expression. The effects of miRNA-132/212 gene-deletion on hippocampal synaptic transmission and levels of cholinergic-signaling elements suggest the existence of a miRNA-132/212-dependent adaptive mechanism safeguarding the functional integrity of synaptic functions in the acute phase of cerebral ischemia.