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

被引:148
作者
Bianchi, M.
Fone, K. F. C.
Azmi, N.
Heidbreder, C. A.
Hagan, J. J.
Marsden, C. A.
机构
[1] GlaxoSmithKline, Dept Biol, CEDD, Harlow CM19 5AW, Essex, England
[2] Univ Nottingham, Sch Med, Queens Med Ctr, Inst Neurosci,Sch Biomed Sci, Nottingham NG7 2UH, England
[3] GlaxoSmithKline, Dept Biol, Ctr Excellence Drug Discovery Psychiat, Verona, Italy
关键词
alpha-tubulin isoforms; early stress; microtubules; novel object recognition;
D O I
10.1111/j.1460-9568.2006.05170.x
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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.
引用
收藏
页码:2894 / 2902
页数:9
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