Figure 1: NH and EE treatments display lifelong protective effects against neurodegeneration in the rat hippocampus. Representative microphotographs (original magnification, 290×) of neurons from CA1 hippocampal field in male rats from the outbred RLA/Verh (Roman low-avoidance) rat line (findings were the same for their RHA/Verh–Roman high-avoidance-counterparts; Meaney et al., 1988; Fernández-Teruel et al., 1997; for similar results with NH treatment). Y: Young, untreated, 5-month-old rats; A: Aged, untreated, 24-month-old rats; NH: aged (24 months old) rats, treated with neonatal handling; EE: aged (24 months old) rats, treated with environmental enrichment from 6 weeks of age until 7 months of age. Brains were embedded in paraffin and cut into 6-μm coronal sections, collected in parallel series, and stained with hematoxylin-eosin for the demonstration of hippocampal cytoarchitecture and atrophic neurons (Fernández-Teruel et al., 1997). The red-blue arrowheads show neurons with normal morphological features, in contrast with atrophic neurons–indicated by the blue arrow- displaying a dystrophic morphology with discernible retraction of the cell body and increased eccentricity. Note that Y rats have normal neurons, whereas A rats show neuronal atrophy (i.e. neurodegeneration), which is prevented by NH and EE treatments (as well as by combining both treatments; not shown; Fernández-Teruel et al., 1997). The semi-quantitative evaluation of neuronal atrophy in several sections (from medial to caudal hippocampus), per rat and experimental group, from CA1, CA2, CA4, fascia dentata and the hylus, can be seen in Fernández-Teruel et al. (1997, Table IV). In short, we used a scoring scale of “–” (no atrophy, 0 points) and “+, ++, +++, ++++” (1–4 points of neuronal atrophy, for each section and rat of a given experimental group). Results: According to this scoring method, and pooling the results from both RLA/Verh and RHA/Verh rats, the 3 treated (NH, EE and NH + EE) groups and the 5 hippocampal regions, the mean neuronal atrophy scores were: Y rats, 0.5; A rats, 3.2; “treated and aged” (NH, EE or NH + EE) groups, 0.7 (P < 0.05 between the “treated and aged” group and the A group; see Table IV by Fernández-Teruel et al., 1997). These anti-neurodegeneration effects were paralleled by complete prevention of the age-related hippocampus-dependent spatial learning/memory deficits in NH-, EE- and NH + EE-treated rats (Fernández-Teruel et al., 1997; figure partially adapted from Fernández-Teruel et al., 1997).