Co-creating Humanistic AI AgeTech to Support Dynamic Care Ecosystems: A Preliminary Guiding Model.

As society rapidly digitizes, successful aging necessitates using technology for health and social care and social engagement. Technologies aimed to support older adults (e.g.

Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP.

Glutamate regulates the function of central nervous system (CNS), in part, through the cAMP and/or IP3/DAG second messenger-associated metabotropic glutamate receptors (mGluRs). The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has been extensively used to elucidate potential physiological and pathophysiological functions of mGluR5. Unfortunately, recent evidence indicates significant non-specific actions of MPEP, including inhibition of NMDA receptors.

Novel neuroprotective tripeptides and dipeptides.

It has long been recognized that thyrotropin-releasing hormone (TRH) and certain TRH analogues are neuroprotective in a variety of animal models of CNS trauma. In addition to these neuroprotective actions, TRH and most TRH analogues have other physiological actions that may not be desirable for treatment of acute injury, such as analeptic, autonomic, and endocrine effects. We have developed a series of dual-substituted TRH analogues that have strong neuroprotective actions, but are largely devoid of these other physiological actions.

Neuroprotective activity of the mGluR5 antagonists MPEP and MTEP against acute excitotoxicity differs and does not reflect actions at mGluR5 receptors.

1 Neuroprotection has been reported after either activation or blockade of the group I metabotropic glutamate receptor subtype 5 (mGluR5). However, some recent evidence suggests that protection provided by mGluR5 antagonists may reflect their ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity. 2 Here, in both rat and mouse cortical neurons, we compare the neuroprotective actions of two mGluR5 antagonists: 2-methyl-6-(phenylethynyl)-pyridine (MPEP), which has been commonly used and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), a more recently developed compound believed to have greater mGluR5 selectivity.

The "dark side" of endocannabinoids: a neurotoxic role for anandamide.

Endocannabinoids, including 2-arachidonoylglycerol and anandamide (N-arachidonoylethanolamine; AEA), have neuroprotective effects in the brain through actions at CB1 receptors. However, AEA also binds to vanilloid (VR1) receptors and induces cell death in several cell lines. Here we show that anandamide causes neuronal cell death in vitro and exacerbates cell loss caused by stretch-induced axonal injury or trophic withdrawal in rat primary neuronal cultures.

Modulation of metabotropic glutamate receptors as potential treatment for acute and chronic neurodegenerative disorders.

It is well established that in both animal models and humans, traumatic or ischemic insults to the brain or spinal cord cause an excessive release of excitatory amino acids, including glutamate. Moreover, multiple in vivo and in vitro studies show that excessive release of glutamate, and subsequent activation of ionotropic (iGluRs) and metabotropic (mGluRs) classes of glutamate receptors, cause neuronal cell death through either necrosis or apoptosis. Although studies in adult animals have demonstrated the neuroprotective effects of inhibiting iGluRs following central nervous system injury, results from human trials have been disappointing.

Modulation of stretch-induced enhancement of neuronal NMDA receptor current by mGluR1 depends upon presence of glia.

Stretching of cultured neurons has been used to model diffuse axonal injury associated with brain trauma. N-Methyl-D-aspartate receptor (NMDAR) activation and group I metabotropic glutamate receptors (mGluRs) are implicated in the pathophysiology of such injury. Here we detail the effects of culture condition and mGluR1 modulation on stretch-enhanced NMDA receptor activity, and show the presence of mGluR1 in addition to mGluR5 in glia.

Modulation of epileptiform burst frequency by the metabotropic glutamate receptor subtype mGluR3.

Spontaneous epileptiform burst activity occurs in acute hippocampal slice dentate granule cells perfused with 10mM potassium and 0.5mM calcium [J. Neurophys.

Ceramide-induced neuronal apoptosis is associated with dephosphorylation of Akt, BAD, FKHR, GSK-3beta, and induction of the mitochondrial-dependent intrinsic caspase pathway.

Neuronal apoptosis has been implicated as an important mechanism of cell death in acute and chronic neurodegenerative disorders. Ceramide is a product of sphingolipid metabolism which induces neuronal apoptosis in culture, and ceramide levels increase in neurons during various conditions associated with cell death. In this study we investigate the mechanism of ceramide-induced apoptosis in primary cortical neuronal cells.

Neuronal and glial mGluR5 modulation prevents stretch-induced enhancement of NMDA receptor current.

Neuronal stretching in culture has been used to model diffuse axonal injury caused by head trauma, and activation of N-methyl-D-aspartate receptors (NMDARs) has been implicated in the pathophysiology of such injury. Here we report the effects of modulating injury severity and the metabotropic glutamate receptor subtype 5 (mGluR5) on NMDAR activity after stretch injury. Following mild stretch, cortical neurons plated upon a confluent layer of astrocytes (NG) exhibited both increased maximal current (I(NMDA)) and reduction in the voltage-dependent Mg2+ block.