Isolation rearing induces recognition memory deficits accompanied by cytoskeletal alterations in rat hippocampus

Abstract

Social isolation from weaning affects hippocampal structure and function in the rat. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal development and organization. Accordingly, the present paper investigated the effects of social isolation on hippocampal levels of alpha-tubulin isoforms associated with microtubule dynamics, the dendritic marker MAP-2 and alterations in locomotor activity and recognition memory. Male Lister Hooded rats (postnatal day 25-28) were housed either in groups or singly (isolated animals) for 30 days. Locomotor activity in a novel arena and novel object recognition were monitored in activity boxes. The hippocampus was dissected out 18 h after the novel object recognition task. Levels of alpha-tubulin isoforms and MAP-2 were analysed using Western blots. The experiments were conducted in duplicate, using two batches of rats obtained from different suppliers. Isolated animals were hyperactive and showed recognition memory deficits in the novel object recognition task. These behavioural alterations were accompanied by specific alterations in hippocampal alpha-tubulin isoforms and decreased MAP-2 expression. The results confirm that rearing rats in isolation produces hyperactivity and cognitive deficits. The behavioural alterations were accompanied by hippocampal cytoskeletal changes consistent with microtubule stabilization, and by decreased MAP-2 expression. These findings are indicative of an abnormal development of synaptic connections and/or reductions in neuronal cell number. The developmental structural abnormalities in the hippocampus may contribute to the cognitive impairments which result from isolation rearing in rats.

Intrahippocampal Transplantation of Transgenic Neural Precursor Cells Overexpressing Interleukin-1 Receptor Antagonist Blocks Chronic Isolation-Induced Impairment in Memory and Neurogenesis

“…Our findings that chronic isolation significantly impaired contextual fear conditioning and spatial memory, but not auditory-cued fear conditioning or nonspatial performance in the water maze are consistent with previous reports that either acute (Barrientos et al, 2003) or chronic (Kogan et al, 2000;Bianchi et al, 2006) isolation markedly impaired hippocampal-dependent memory, but not memory that does not depend on hippocampal functioning. Previous studies on the effects of chronic stress on hippocampal neurogenesis demonstrated decreased cell proliferation in the dentate gyrus following chronic isolation (Dong et al, 2004), as well as several other chronic stressors (Simon et al, 2005; Lee et al, 2006;.…”

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

“…The NOR task was performed as described (5). An inter-trial interval (ITI) of 2 h was used between the familiarization and the choice trial.…”

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

“…In addition, these circuits also appear to be capable of integrating over much longer time scales (i.e., days to months), thus allowing the functionality of these structures to be shaped by relatively subtle changes in the environment. Consistent with this idea, in animal studies, alterations in the external environment which enhance sensory stimulation (i.e., environmental enrichment; EE), or conversely, environmental conditions that deprive the animal of stimuli for many weeks, have been found to profoundly affect/shape cognitive capacity (van Praag et al 2000;Bruel-Jungerman et al 2005;Bianchi et al 2006). At a cellular level, EE triggers an increase in the generation and integration of adult-born neurons into the granule cell layer (GCL) of the hippocampus and increases dendritic branching complexity and synapse formation in excitatory neurons of the hippocampus (Kempermann et al 1997(Kempermann et al , 1998van Praag et al 2000;Faherty et al 2003).…”

“…At a cellular level, EE triggers an increase in the generation and integration of adult-born neurons into the granule cell layer (GCL) of the hippocampus and increases dendritic branching complexity and synapse formation in excitatory neurons of the hippocampus (Kempermann et al 1997(Kempermann et al , 1998van Praag et al 2000;Faherty et al 2003). Further, reduced sensory stimulation leads to a decrease in progenitor proliferation and dendrite branch patterns, which likely results in the wellcharacterized increase in depression and reduced cognitive capacity (Silva-Gomez et al 2003;Bianchi et al 2006;Ibi et al 2008). Importantly, retrospective analysis of humans exposed to psychosocial or behavioral enrichment appears to support the findings of animal studies (Cotman and Berchtold 2002;Agrigoroaei and Lachman 2011;Erickson et al 2011).…”