Mechanisms mediating brain plasticity: IGF1 and adult hippocampal neurogenesis.

Llorens-Martín M, Torres-Alemán I, Trejo JL.

The Neuroscientist.
doi: 10.1177/1073858408331371.

This review addresses the role of serum insulin-like growth factor 1 (IGF1) as one mechanism of adult neural plasticity, specifically, its regulation of hippocampal neurogenesis among other plasticity-related processes. It is suggested that IGF has been reused advantageously both for the control of energy expenditure as a function of the organism's activity and to protect, repair, and plastically modulate the brain. Moreover, because as the main source of IGF1 in the adult organism is outside the brain and its presence in this organ is a function of the activity, IGF1 becomes an ideal factor to induce plastic/neuroprotective functions as a function of the organism's activity. The link for this point of view comes from the original function of IGF1 during ontogeny/phylogeny, the promotion of cell survival and control of neural cell numbers, whereas one of the IGF1 functions in the adult brain is the control of hippocampal neurogenesis. The investigation of the IGF1 role as mediator of exercise effects suggests that many but not all the effects of physical activity are mediated by IGF1. These investigations have contributed to delimit the role of IGF1 as mediator of exercise actions, but at the same time are unveiling new roles for serum IGF1 inside the brain.

Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal.

Hernández-Rabaza V, Llorens-Martín M, Velázquez-Sánchez C, Ferragud A, Arcusa A, Gumus HG, Gómez-Pinedo U, Pérez-Villalba A, Roselló J, Trejo JL, Barcia JA, Canales JJ.

doi: 10.1016/j.neuroscience.2008.11.054.

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a "purely" contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies.


Centro de Biología Molecular Severo Ochoa (CBMSO) Universidad Autónoma de Madrid (Campus de Cantoblanco)
C/ Nicolás Cabrera 1 - 28049 Madrid (Spain)

María Llorens-Martín (PI)
+34 911964632