An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat

Ordy, J. M.; Thomas, Garth J.; Volpe, Bruce T.; Dunlap, William P.; Colombo, Piergiuseppe

doi:10.1016/s0197-4580(88)80131-3

Cited by 110 publications

(45 citation statements)

References 39 publications

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“…The present finding that aged rats exhibited impaired working memory retention is essen tially consistent with other reports (8,9). However, Willig et al (10) and Aggleton et al (12) found no significant age decline in the working memory using a comparable T-maze task.…”

Section: Discussionsupporting

confidence: 93%

“…Dunnet et al (9) have reported, using a 2-lever operant chamber for delayed nonmatching to position task, that aged rats showed a progressively greater impaired performance as the delays lengthened. On the other hand, Ordy et al (8) have reported that aged Long-Evans rats exhibited parallel decrease in choice accuracy at 10, 90 and 180 sec delays compared with young and middle aged groups. We employed the wide ranged delay intervals (5 to 300 sec) on the assumption that memory impairment in aged rats should be greater with extended de lay intervals.…”

Section: Discussionmentioning

confidence: 95%

“…A few reports have fo cused on this point but conflicting results were obtained in these studies. Some investigators reported impaired working memory retention (8,9), but others demonstrated preservation of the memory (10 -12) in aged rats. In the present study, we employed delayed non matching to a position task, which is favorable for assessing the retention of spatial working memory (13).…”

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confidence: 99%

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Working Memory Deficit in Aged Rats in Delayed Nonmatching to Position Task and Effect of Physostigmine on Performance of Young and Aged Rats.

Ohta

Matsumoto

et al. 1991

Jpn.J.Pharmacol

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-Young (5 month) and aged (23 month) male rats were tested in delayed nonmatching to position task using a T-maze, and their ability of working memory re tention was assessed over interrun intervals ranging between 5 and 300 sec. There were no significant age differences in pretest performance at 0 sec interval, but signifi cant memory loss was observed in aged rats when tested with the interrun intervals. Physostigmine (0.1 and 0.2 mg/kg) improved this age-related decline in working mem ory in a dose-dependent manner, whereas the treatment slightly but not significantly improved the performance of young rats. These results suggest that the central cho linergic system in aged rats was functionally deteriorated and that stimulation of the system could enhance working memory retention in aged rats.It is well-established that aged rodents ex hibit impaired performance on a variety of learning and memory tasks (1-5), but only lim ited information is available on working mem ory in aged rodents. To study this type of memory, an 8-arm radial maze task has been the most commonly used. Using the radial maze task, impaired performance of aged rats has been demonstrated mainly in acquisition of the task (5-7). As for the retention of working memory, it still remains unclear whether it is actually impaired in aged rats. Therefore, one of the purposes of the present study is to test the ability of working memory retention in aged rats. A few reports have fo cused on this point but conflicting results were obtained in these studies. Some investigators reported impaired working memory retention (8, 9), but others demonstrated preservation of the memory (10 -12) in aged rats. In the present study, we employed delayed non matching to a position task, which is favorable for assessing the retention of spatial working memory (13). In addition, such delayed re sponse tasks corresponded well to memory tasks in humans. A number of reports have proved these delayed response tasks to be appropriate and useful in studies of ex perimental amnesia in monkeys (14, 15) and memory dysfunction in human dementia (16). We also tested the effect of physostigmine (PHY) on the performance in this task to test the possibility that stimulation of the cho linergic system could ameliorate age-related decline in working memory.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Working Memory Deficit in Aged Rats in Delayed Nonmatching to Position Task and Effect of Physostigmine on Performance of Young and Aged Rats.

Ohta

Matsumoto

et al. 1991

Jpn.J.Pharmacol

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“…brillary tangles (A␤ 25/26 -35 ) and in the degenerating hippocampal CA1 neurons with intracellular neurofibrillary tangles (A␤ [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] ), in AD brains, but not in agematched control subjects. 15 Deposits of A␤ [25][26][27][28][29][30][31][32][33][34][35] peptide after its injection have not yet been characterized by IHC, for lack of specific and selective antibodies.…”

Section: Discussionmentioning

confidence: 99%

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Zussy

Brureau

Delair

et al. 2011

The American Journal of Pathology

116

129

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Alzheimer's disease (AD) is a neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss. The major component of senile plaques is an amyloid ␤ protein (A␤) formed by pathological processing of the A␤ precursor protein. We assessed the time-course and regional effects of a single intracerebroventricular injection of aggregated A␤ fragment 25-35 (A␤ 25-35 ) in rats. Using a combined biochemical, behavioral, and morphological approach, we analyzed the peptide effects after 1, 2, and 3 weeks in the hippocampus, cortex, amygdala, and hypothalamus. The scrambled A␤ 25-35 peptide was used as negative control. The aggregated forms of A␤ peptides were first characterized using electron microscopy, infrared spectroscopy, and Congo Red staining. Intracerebroventricular injection of A␤ 25-35 decreased body weight, induced short-and long-term memory impairments, increased endocrine stress, cerebral oxidative and cellular stress, neuroinflammation, and neuroprotective reactions, and modified endogenous amyloid processing, with specific time-course and regional responses. Moreover, A␤ 25-35 , the presence of which was shown in the different brain structures and over 3 weeks, provoked a rapid glial activation, acetylcholine homeostasis perturbation, and hippocampal morphological alterations. Alzheimer's disease (AD) is a chronic neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss in brain areas responsible for learning and memory impairments. 1 The major component of senile plaques is an amyloid ␤ protein (A␤) derived from amyloid precursor protein (APP). Genetic, cell biological, and postmortem studies on AD brain, together with A␤ neurotoxicity findings, gave rise to the amyloid cascade hypothesis to explain A␤-associated neurodegenerative processes. 2 In normal healthy individuals, A␤ peptides are present only in small quantities, as soluble monomers that circulate in cerebrospinal fluid and blood. In AD patients, A␤ peptides, which vary in length from 40 to 43 amino acids, accumulate as insoluble fibrillar deposits. 3 When cultured rat hippocampal neurons are exposed to aggregated A␤ peptides, their neurites adopt a dystrophic appearance and become comparable to those observed surrounding and infiltrating senile plaques. This observation suggested that A␤ is responsible for the neuritic abnormalities in AD pathology. 4 Structure-activity studies revealed that peptides containing the highly hydrophobic 25-35 region formed stable aggregates and mediated neuronal death by necrosis or apoptosis. 5,6,7 The truncated A␤ 25-35 fragment includes extracellular and intramembrane residues that have been reported to represent an active region of A␤. 8

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“…The dentate gyrus can be unaffected -early beta and gamma irradiation reduces cell numbers in the CA1-3 regions [99,100] with additional damage in the cerebellum, but not in the dentate gyrus. Oxygen deprivation (as in cerebral ischemia) leaves the dentate intact but selectively destroys hippocampal CA region pyramidal neurons [101,102] as seen in some ASD subjects [52] . While these studies confirm the regional vulnerability of the hippocampus, clearly the location and type of damage does not depend on the presence of dividing cells.…”

Section: Dividing Cellsmentioning

confidence: 99%

Environmental Factors and Limbic Vulnerability in Childhood Autism

Lathe¹

2008

American J. of Biochemistry and Biotechnology

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Abstract:The rise in prevalence of autism spectrum disorders (ASD) is suggestive of a new etiology. Diagnostic substitution alone is unlikely to account for the increase, while genetic association with detoxification gene alleles points to an environmental contribution. Subtle structural anomalies in the ASD brain are widespread but limbic damage seems important for the development of behaviors diagnostic of ASD. The limbic brain is especially susceptible to environmental challenge: internal sensing, physiological feedback and neuroinflammatory processes may underlie this sensitivity to insult. Primary damage leading to ASD in later life is likely to take place in utero and/or in the immediate postnatal period. Despite evidence of heavy metal involvement, a causal connection may not yet be concluded because subjects exposed to metals tend to be exposed to other environmental agents. Because maternal minerals and lipids are supplied to the unborn child, historic toxic exposure of the mother may be pivotal. A two-hit combination of genetic susceptibility and environmental challenge is argued to underlie the rise in ASD.

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An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat

Cited by 110 publications

References 39 publications

Working Memory Deficit in Aged Rats in Delayed Nonmatching to Position Task and Effect of Physostigmine on Performance of Young and Aged Rats.

Working Memory Deficit in Aged Rats in Delayed Nonmatching to Position Task and Effect of Physostigmine on Performance of Young and Aged Rats.

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Environmental Factors and Limbic Vulnerability in Childhood Autism

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