Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats

Pham, T. M.; Söderström, Stine; Winblad, Bengt; Mohammed, Abdul K.

doi:10.1016/s0166-4328(99)00019-4

Cited by 147 publications

(71 citation statements)

References 32 publications

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“…Notwithstanding this differential regula- tion, hippocampal and frontal cortex NGF levels are alike in control and APP23 animals. It has been speculated that lack of adequate environmental stimulation might be of importance in age-related behavioral and neurochemical deficits, because novel environments caused significant changes in hippocampal NGF levels (Mohammed et al 1990;Pham et al 1999). In contrast, the present work may indicate that after onset of the disease, training may have detrimental effects, as has also been observed in young normal subjects (Markowska et al 1994).…”

Section: Discussionmentioning

confidence: 47%

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Hellweg¹,

Lohmann²,

Huber³

et al. 2006

Learn. Mem.

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Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease (AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and APP23 animals in the radial maze. In contrast, performance in the complex maze was better in wild-type than APP23 animals. Contrary to the wild-type, hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and frontal cortex NGF levels in APP23 animals correlated with the time to solve the complex maze, but correlated inversely with escape time in wild-type animals. NT-3 levels were alike in wild-type and APP23 animals and were unchanged even after training. Both types of mazes depend on hippocampal integrity to some extent. However, according to the cognitive mapping theory of spatial learning, the complex maze because of the increased complexity of the environment most likely depends more strongly on preserved hippocampal function than the radial maze in the working memory configuration applied here. Greater impairment in complex maze performance than in radial maze performance thus resembles the predominant affliction of the loss of hippocampal function in human AD. NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike.

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Section: Discussionmentioning

confidence: 47%

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Hellweg¹,

Lohmann²,

Huber³

et al. 2006

Learn. Mem.

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“…Interestingly, controls that were prevented from getting food storing experience were found to have a higher proportion of apoptotic cells (i.e., programmed cell death) relative to birds that experienced storing food (Clayton, 1995). In addition, studies of rodents and birds exposed to an enriched environment have shown increases in the density of neurons, size of cell bodies, dendritic branching, spine density, and levels of nerve growth factor (Greenough et al, 1973;Pham et al, 1999;Pinaud et al, 2002;Kolb et al, 2003). It has been shown that the primate hippocampus generates new Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Gray Matter Differences Correlate with Spontaneous Strategies in a Human Virtual Navigation Task

Bohbot¹,

Lerch²,

et al. 2007

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Young healthy participants spontaneously use different strategies in a virtual radial maze, an adaptation of a task typically used with rodents. Functional magnetic resonance imaging confirmed previously that people who used spatial memory strategies showed increased activity in the hippocampus, whereas response strategies were associated with activity in the caudate nucleus. Here, voxel based morphometry was used to identify brain regions covarying with the navigational strategies used by individuals. Results showed that spatial learners had significantly more gray matter in the hippocampus and less gray matter in the caudate nucleus compared with response learners. Furthermore, the gray matter in the hippocampus was negatively correlated to the gray matter in the caudate nucleus, suggesting a competitive interaction between these two brain areas. In a second analysis, the gray matter of regions known to be anatomically connected to the hippocampus, such as the amygdala, parahippocampal, perirhinal, entorhinal and orbitofrontal cortices were shown to covary with gray matter in the hippocampus. Because low gray matter in the hippocampus is a risk factor for Alzheimer's disease, these results have important implications for intervention programs that aim at functional recovery in these brain areas. In addition, these data suggest that spatial strategies may provide protective effects against degeneration of the hippocampus that occurs with normal aging.

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“…C57BL/6 learning-impaired mice [52] show increased survival of hippocampal cells if exposed to an EC, while DHA prolongs cell survival in retinal photoreceptors [53]. Brains of EC rodents exhibit increased NGF (nerve growth factor) expression [54]; likewise DHA administration can increase the expression of NGF [55]. Brains of EC rodents also exhibit increased expression of mRNA for BDNF [8]; BDNF modulates synapsin 1 levels during learning [56], and giving UMP plus DHA increases synapsin 1 levels in gerbil brain [14].…”

Section: Discussionmentioning

confidence: 99%

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Holguin

Huang

Liu

et al. 2008

Behavioural Brain Research

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Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDPcholine. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively-impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg ) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal-and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; coadministration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP, DHA, nor both compounds affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that coadministration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all p<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all p<0.01) and total brain phospholipids (p<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.

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Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats

Cited by 147 publications

References 32 publications

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Gray Matter Differences Correlate with Spontaneous Strategies in a Human Virtual Navigation Task

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

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