Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice.

Aging is accompanied by increased neuroinflammation, synaptic dysfunction, and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events.

Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome.

The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits.

Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse.

The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory. Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia. HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition.

CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity.

The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on the CNS insult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions.

Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density.

Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive function; however, the in vivo effect of enhanced Reelin signaling on cognitive function and synaptic plasticity in wild-type mice is unknown. The present studies test the hypothesis that in vivo enhancement of Reelin signaling can alter synaptic plasticity and ultimately influence processes of learning and memory.

Secretin deficiency causes impairment in survival of neural progenitor cells in mice.

Hippocampal neurogenesis is the lifelong production of new neurons in the central nervous system (CNS), and affects many physiological and pathophysiological conditions, including neurobehavioral disorders. The early postnatal stage is the most prominent neurogenesis period; however, the functional role of neurogenesis in this developing stage has not been well characterized. To understand the role of hippocampal neurogenesis in the postnatal developing period, we analyzed secretin, a neuropeptide, which is expressed significantly higher in the development stage.

Reelin and apoE actions on signal transduction, synaptic function and memory formation.

Low-density-lipoprotein receptors (LDLRs) are an evolutionarily ancient surface protein family with the ability to activate a diversity of extracellular signals across the cellular membrane in the adult central nervous system (CNS). Their intimate roles in modulating synaptic plasticity and their necessity in hippocampal-dependent learning and memory have only recently come to light. Two known LDLR ligands, specifically apolipoprotein E (apoE) and reelin, have been the most widely investigated in this regard.

Increased vulnerability of hippocampal neurons with age in culture: temporal association with increases in NMDA receptor current, NR2A subunit expression and recruitment of L-type calcium channels.

Excessive glutamate (Glu) stimulation of the NMDA-R is a widely recognized trigger for Ca(2+)-mediated excitotoxicity. Primary neurons typically show a large increase in vulnerability to excitotoxicity with increasing days in vitro (DIV). This enhanced vulnerability has been associated with increased expression of the NR2B subunit or increased NMDA-R current, but the detailed age-courses of these variables in primary hippocampal neurons have not been compared in the same study.