Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Abstract

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O2 hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Cav 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Cav 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Cav 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.

Simultaneous monitoring of mouse grip strength, force profile, and cumulative force profile distinguishes muscle physiology following surgical, pharmacologic and diet interventions

“…In healthy individuals, we expect that grip strength and force profile should be highly correlated. Indeed, peak grip strength and cumulative force profile are often used interchangeably to report about muscle 12 , 13 or neural physiology 14 – 16 . However, it is appreciated that muscle impairment likely differs depending upon the disease context.…”

The regulatory role of NAAG-mGluR3 signaling on cortical synaptic plasticity after hypoxic ischemia

“…When NAAG levels increased 12–24 h after HI, so did mGluR3 expression, and NAAG was positively correlated with mGluR3, implying that NAAG binding to mGluR3 increased and downstream molecular pathways were activated during this period. The main function of voltage-sensitive Ca 2+ channels is to control Ca 2+ entry into the cell to influence the vesicular neurotransmitter release and to bind to and regulate Ca 2+ -dependent neurotransmitter release from the cytoplasmic domain of the transmembrane polypeptide of syph [ 43 , 44 ]. Therefore, this study further confirmed the effect of NAAG on syph and SVs.…”

Environmental Enrichment Improves the Recognition Memory in Adult Mice Following Social Isolation via Downregulation of Kv4.2 Potassium Channels

“…Speci cally, EE has been found to improve recognition memory in animal models of normal aging and disease by stimulating synaptic plasticity via increased numbers of dendritic spines and enhanced synaptic function [16][17][18]. EE is also known to have an effect on neuronal activity through regulating the expression of ion channels and synaptic proteins of many brain areas including the PFC [19], hippocampus [20,21] and NAc [22]. Thus, it is not surprising that EE may exert neuroplasticity and neuroprotective effects in adult mice following SI.…”