Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections (original) (raw)

Reelin Regulates Postnatal Neurogenesis and Enhances Spine Hypertrophy and Long-Term Potentiation

Reelin, an extracellular protein essential for neural migration and lamination, is also expressed in the adult brain. To unravel the function of this protein in the adult forebrain, we generated transgenic mice that overexpress Reelin under the control of the CaMKII promoter. Overexpression of Reelin increased adult neurogenesis and impaired the migration and positioning of adult-generated neurons. In the hippocampus, the overexpression of Reelin resulted in an increase in synaptic contacts and hypertrophy of dendritic spines. Induction of long-term potentiation (LTP) in alert-behaving mice showed that Reelin overexpression evokes a dramatic increase in LTP responses. Hippocampal field EPSP during a classical conditioning paradigm was also increased in these mice. Our results indicate that Reelin levels in the adult brain regulate neurogenesis and migration, as well as the structural and functional properties of synapses. These observations suggest that Reelin controls developmental processes that remain active in the adult brain.

Reelin affects chain-migration and differentiation of neural precursor cells

Molecular and Cellular Neuroscience, 2009

In the adult mammalian brain, multipotential neural stem cells (NSC) persist throughout life in areas where neurogenesis is maintained. A distinctive trait of NSCs growing in vitro as neurospheres (NS), is their ability to self-renew, differentiate and migrate to sites of injury, such as gliomas. We have studied the role of Reelin, an extracellular matrix protein involved in brain development, in NSCs derived from normal newborn mice or from reeler, a natural mutant in which Reelin is not expressed. We show that the absence of Reelin negatively affects proliferation, NS-forming ability, and neuronal differentiation. Reeler NSCs are unable to migrate in chains, a migration mode typical of neural precursors homing to injury sites in adult CNS. All these effects are partially rescued by ectopic Reelin supplementation. Finally, we show that reeler NSCs fail to migrate in vivo towards gliomas. Overall, our results indicate that Reelin affects all major features of postnatal NSCs, and that it is required for the proper homing of NSCs to tumor sites in adult brain.

Study of the expression and functional mechanisms of the extracellular matrix protein, reelin, during prenatal development of the rodent brain

2011

Reelin is an extracellular matrix protein that plays a role in neuronal migration and positioning during development of the central nervous system (CNS) (reviewed by Huang and D'Arcangelo, 2008). Besides this role in early development, reelin is also expressed in the adult brain, where it has been related with synaptic plasticity by enhancing the induction and maintenance of long-term potentiation (Weeber et al., 2002; Beffert et al., 2006), and with dendrite and dendritic spine development (Dong et al., 2003; Niu et al., 2004; 2008; Beffert et al., 2006; Campo et al., 2009). In 1998 was reported the decreased expression of reelin protein and mRNA (about 50%) in post-mortem brains of schizophrenic patients (Impagnatiello et al., 1998). After that seminal finding, other reports also found significant reductions of reelin levels in post-mortem brains of patients with schizophrenia, bipolar disorder, major depression (Fatemi et al., 2000; Guidotti et al., 2000; Fatemi et al., 2001b...