Dataset Information

Long-term perturbation of spine plasticity results in distinct impairments of cognitive function.

ABSTRACT: Dendritic spines serve as the post-synaptic structural component of synapses. The structure and function of dendritic spines are dynamically regulated by a number of signaling pathways and allow for normal neural processing, whereas aberrant spine changes are thought to contribute to cognitive impairment in neuropsychiatric and neurodegenerative disorders. However, spine changes within different brain regions and their contribution to specific cognitive functions, especially later in adulthood, is not well understood. In this study, we used late-adult KALRN-deficient mice as a tool to investigate the vulnerability of different cognitive functions to long-term perturbations in spine plasticity in different forebrain regions. We found that in these mice, loss of one or both copies of KALRN lead to genotype and brain region-dependent reductions in spine density. Surprisingly, heterozygote and knockout mice showed differential impairments in cognitive phenotypes, including working memory, social recognition, and social approach. Correlation analysis between the site and magnitude of spine loss and behavioral alterations suggests that the interplay between brain regions is critical for complex cognitive processing and underscores the importance of spine plasticity in normal cognitive function. Long-term perturbation of spine plasticity results in distinct impairments of cognitive function. Using genetically modified mice deficient in a central regulator of spine plasticity, we investigated the brain region-specific contribution of spine numbers to various cognitive functions. We found distinct cognitive functions display differential sensitivity to spine loss in the cortex and hippocampus. Our data support spines as neuronal structures important for cognition and suggest interplay between brain regions is critical for complex cognitive processing.

SUBMITTER: Vanleeuwen JE

PROVIDER: S-EPMC3493825 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term perturbation of spine plasticity results in distinct impairments of cognitive function.

Vanleeuwen Jon-Eric JE Penzes Peter P

Journal of neurochemistry 20121011 5

Dendritic spines serve as the post-synaptic structural component of synapses. The structure and function of dendritic spines are dynamically regulated by a number of signaling pathways and allow for normal neural processing, whereas aberrant spine changes are thought to contribute to cognitive impairment in neuropsychiatric and neurodegenerative disorders. However, spine changes within different brain regions and their contribution to specific cognitive functions, especially later in adulthood, ...[more]

PMID: 22862288

Similar Datasets

Project description:Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

Dataset Information

Long-term perturbation of spine plasticity results in distinct impairments of cognitive function.

Publications

Long-term perturbation of spine plasticity results in distinct impairments of cognitive function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets