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

Abstract

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. Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory. The present study suggests that an acute elevation of in vivo Reelin can have longterm effects on synaptic function and cognitive ability in wild-type mice.

The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior

“…An association between spine and spine-synapse density, hippocampal LTP and memory impairments has been observed in other animal models. For instance, a single intraventricular injection of Reelin, a modulator of synaptic function implicated in several cognitive disorders including autism and schizophrenia, leads to an increase in dendritic spine density, enhanced hippocampal CA1 LTP and improved associative and spatial learning and memory, whereas lack of its receptors VLDLR and apoER2 is responsible for deficits in LTP and contextual fear conditioning (Weeber et al 2002;Rogers et al 2011). In contrast to this postsynaptic phenotype, our data do not indicate alterations in presynaptic PPF.…”

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

“…Moreover, behavioral and memory deficits are also observed after Reelin knock-down in the prefrontal cortex in adult rats (Brosda et al, 2011). The important role of Reelin in modulating synaptic functions has also been highlighted by the enhancing effect of intraventricular infusions of recombinant Reelin on cognitive performance, synaptic plasticity, and dendritic spine density in wild-type (Rogers et al, 2011) and Reelin heterozygous mice (Rogers et al, 2012). Interestingly, also exercise during pregnancy induces Reelin expression in offspring and mitigates plaque pathology in AD-mice (Herring et al, 2012b).…”

Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein

“…Incubation with Reelin-PD keeps Dab1 levels low for as long as 24 h, indicating that N-t cleavage plays a major role in inactivating the Reelin-Dab1 pathway. In recent years, up-regulation of this pathway has been suggested to be beneficial for the treatment of neuropsychiatric diseases (19,21,53,54). In particular, a single injection of Reelin protein into the ventricle has been shown to have a beneficial effect on synaptic transmission, learning, and memory (19).…”

“…However, the mechanisms involved in regulating Reelin activity are largely unknown. Furthermore, there have been no methods developed to augment Reelin activity except for the direct injection of partially purified Reelin protein into the brain (19).…”