A pathophysiological framework of hippocampal dysfunction in ageing and disease

Small, Scott A.; Schobel, Scott; Buxton, Richard B.; Witter, Menno P.; Barnes, Carol A.

doi:10.1038/nrn3085

Cited by 799 publications

(789 citation statements)

References 186 publications

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“…In line with a recent study that reported greater hippocampal shape alterations in patients with schizophrenia and prior comorbid alcohol use disorders (Smith et al, 2011), we hypothesised that cannabis use would exert an additional effect on the hippocampal pathology typically observed in schizophrenia, particularly in the anterior hippocampus (Csernansky et al, 2002;Small et al, 2011;Tamminga et al, 2010).…”

Section: Introductionsupporting

confidence: 64%

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Alteration to hippocampal shape in cannabis users with and without schizophrenia

Solowij

Walterfang

Lubman

et al. 2013

Schizophrenia Research

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Abnormalities in hippocampal morphology are characteristic of schizophrenia and have also been reported in chronic cannabis users. There is a paucity of research investigating potential additive effects of cannabis use on brain pathology associated with schizophrenia. In this study, we performed hippocampal shape analysis in cannabis-using and non-using patients with schizophrenia, healthy cannabis users and healthy non-using controls. Hippocampal shape changes were observed in each group relative to controls, with the greatest degree of alterations (i.e., deflations across the hippocampus, and with an anterior predisposition), in cannabis-using schizophrenia patients. These alterations were associated with cannabis use patterns and psychotic symptoms. AbstractAbnormalities in hippocampal morphology are characteristic of schizophrenia and have also been reported in chronic cannabis users. There is a paucity of research investigating potential additive effects of cannabis use on brain pathology associated with schizophrenia. In this study we performed hippocampal shape analysis in cannabis-using and non-using patients with schizophrenia, healthy cannabis users and healthy non-using controls. Hippocampal shape changes were observed in each group relative to controls, with the greatest degree of alterations (i.e., deflations across the hippocampus, and with an anterior predisposition), in cannabis-using schizophrenia patients. These alterations were associated with cannabis use patterns and psychotic symptoms.

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Section: Introductionsupporting

confidence: 64%

“…Hippocampal pathophysiology is evident in a diverse range of disorders that appear to differentially target distinct subregions of the hippocampus (Small et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Alteration to hippocampal shape in cannabis users with and without schizophrenia

Solowij

Walterfang

Lubman

et al. 2013

Schizophrenia Research

View full text Add to dashboard Cite

show abstract

“…The reason for this large variance is partly the differences in the ability to recruit additional brain areas for task solving, which can partially counterbalance the effect of functional decline [7]. Another factor, which may contribute to the differences in the effect of ageing on cognitive functions, is the large variance in the sensitivity to age-related changes between brain areas and neuronal types [8,9]. Nevertheless, it is generally assumed that age-related progression in synaptic dysfunction and neuronal plasticity impairment are the direct causes of the alterations in neuronal connectivity [10] and thus functional deficits in ageing [11].…”

Section: Functional Histological and Molecular Changes In The Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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“…Based on these results, it was concluded that lesions of the DG decrease the efficiency of spatial pattern separation, which results in impairments on trials with increased spatial proximity and increased spatial similarity among working memory representations. Holden, Hoebel, Loftis, and Gilbert (2012) used an analogous task to that used for rats (Gilbert et al, 2001) to test young participants compared to aged participants who are likely to have DG dysfunction (see Small, et al, 2011). They report that aged participants that do not perform well on standard memory tests are impaired in displaying a pattern separation function.…”

Section: Pattern Separation --Spatial Attributementioning

confidence: 99%

Neurobiological foundations of an attribute model of memory

Kesner¹

2013

CCBR

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Memory is a complex phenomenon due to a large number of potential interactions that are associated with the organization of memory at the psychological and neural system level. In this review article a tripartite, multiple attribute, multiple process memory model with different forms of memory and its neurobiological underpinnings is represented in terms of the nature, structure or content of information representation as a set of different attributes including language, time, place, response, reward value (affect) and visual object as an example of sensory-perception. For each attribute, information is processed in the event-based, knowledge-based, and rule-based memory systems through multiple operations that involve multiple neural underpinnings. Of the many processes associated with the event-based memory system, the emphasis will be placed on short-term or working memory and pattern separation. Of the many processes associated with the knowledgebased memory system, the emphasis will be placed on perceptual processes. Of the many processes associated with the rule-based memory system the emphasis will be on short-term or working memory and paired associate learning. For all three systems data will be presented to demonstrate differential neuroanatomical mediation and where available parallel results will be presented in rodents, monkeys and humans.

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A pathophysiological framework of hippocampal dysfunction in ageing and disease

Cited by 799 publications

References 186 publications

Alteration to hippocampal shape in cannabis users with and without schizophrenia

Alteration to hippocampal shape in cannabis users with and without schizophrenia

The endocannabinoid system in normal and pathological brain ageing

Neurobiological foundations of an attribute model of memory

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