Development of the MAM model of schizophrenia in mice: Sex similarities and differences of hippocampal and prefrontal cortical function

ABSTRACTBackground:Prefrontal cortical lobe function is related to social behavior in humans. We investigated whether performance on tests of prefrontal cortical function was associated with social vulnerability. Associations with non-frontal cognitive function were investigated for comparison.Methods:1216 participants aged 70+ of the Canadian Study of Health and Aging-2 screening examination, who also underwent detailed neuropsychological testing, comprised the study sample. Performance on WAIS-R abstraction, WAIS-R comprehension, Trails B, FAS and category verbal fluency, Block construction, Token Test and Wechsler Memory Scale Information Subset was tested in relation to the participant's level of social vulnerability using regression models adjusted for age, education, sex, frailty, MMSE score, diagnosis of depression, and use of psychoactive medications. Social vulnerability was measured by an index comprising many social problems or “deficits”.Results:The most socially vulnerable group had worse performance on FAS verbal fluency, generating 4.1 fewer words (95% CI: 1.8–6.4, p<0.001) than those in the least socially vulnerable group; those with intermediate social vulnerability generated 2.6 fewer words (95% CI: 0.4–4.8, p = 0.02). Social vulnerability was also associated, though less strongly, with category verbal fluency. The most socially vulnerable people had impaired performance on the Trails B, taking 37 seconds longer (95% CI: 11–63, p = 0.005). These results were independent of age, education, sex, frailty, MMSE score, depression, and psychoactive medications. Social vulnerability was not associated with performance on WAIS-R abstraction, WAIS-R comprehension, Block Design, Token Test or Wechsler Memory Scale testsConclusions:High social vulnerability was associated with impaired performance on verbal fluency and set shifting but not with common sense judgment, abstraction, long-term memory, constructional ability, or language comprehension. The association between social functioning and the cognitive functions subserved by prefrontal cortex warrants further study.

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Dysregulated Prefrontal Cortical RhoA Signal Transduction in Bipolar Disorder with Psychosis: New Implications for Disease Pathophysiology

Cerebral Cortex ◽

10.1093/cercor/bhz070 ◽

2019 ◽

Vol 30 (1) ◽

pp. 59-71

Author(s):

Bailey A Kermath ◽

Amanda M Vanderplow ◽

Michael E Cahill

Keyword(s):

Signal Transduction ◽

Bipolar Disorder ◽

Signal Transduction Pathway ◽

Signal Transduction Pathways ◽

Cellular Functions ◽

Protein Activity ◽

Cortical Function ◽

Prefrontal Cortical ◽

Dorsolateral Prefrontal ◽

Key Factor

Abstract While research has identified alterations in dorsolateral prefrontal cortical function as a key factor to the etiology of bipolar disorder, few studies have uncovered robust changes in protein signal transduction pathways in this disorder. Given the direct relevance of protein-based expressional alterations to cellular functions and because many of the key regulatory mechanisms for the disease pathogenesis likely include alterations in protein activity rather than changes in expression alone, the identification of alterations in discrete signal transduction pathways in bipolar disorder would have broad implications for understanding the disease pathophysiology. As prior microarray data point to a previously unrecognized involvement of the RhoA network in bipolar disorder, here we investigate the protein expression and activity of key components of a RhoA signal transduction pathway in dorsolateral prefrontal cortical homogenates from subjects with bipolar disorder. The results of this investigation implicate overactivation of prefrontal cortical RhoA signaling in specific subtypes of bipolar disorder. The specificity of these findings is demonstrated by a lack of comparable changes in schizophrenia; however, our findings do identify convergence between both disorders at the level of activity-mediated actin cytoskeletal regulation. These findings have implications for understanding the altered cortical synaptic connectivity of bipolar disorder.

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Cannabinoids and prefrontal cortical function: Insights from preclinical studies

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2005.12.002 ◽

2006 ◽

Vol 30 (5) ◽

pp. 680-695 ◽

Cited By ~ 90

Author(s):

Alice Egerton ◽

Claire Allison ◽

Ros R. Brett ◽

Judith A. Pratt

Keyword(s):

Preclinical Studies ◽

Cortical Function ◽

Prefrontal Cortical

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The Physiological Basis of Executive Function and Working Memory

The Neuroscientist ◽

10.1177/107385849600200612 ◽

1996 ◽

Vol 2 (6) ◽

pp. 345-352 ◽

Cited By ~ 33

Author(s):

Mark D'Esposito ◽

Murray Grossman

Keyword(s):

Working Memory ◽

Executive Function ◽

Cognitive Abilities ◽

Brain Regions ◽

Cognitive Domain ◽

Distributed Network ◽

Cortical Function ◽

Physiological Basis ◽

Appropriate Behavior ◽

Prefrontal Cortical

The term “executive function” has been used to capture the highest order of cognitive abilities, including the planning, flexibility, organization and regulation necessary for the execution of an appropriate behavior. Executive function, although an elusive cognitive domain, may be highly dependent on working memory, which refers to the temporary storage and manipulation of information. The physiology of working memory is beginning to be mapped in both monkey and human studies at the neuroanatomical and neurochemical levels. Working memory is likely subserved by a distributed network of brain regions in which the prefrontal cortex is critical, subserving the process of maintaining representations across time. There is also a relationship between dopaminergic projections in the brain and working memory. Improved understanding of the physiological basis of executive functioning and working memory will provide a narrower view of prefrontal cortical function and may lead to new therapies in patients with cognitive dysfunction.

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Persistent impairments in hippocampal, dorsal striatal, and prefrontal cortical function following repeated photoperiod shifts in rats

Experimental Brain Research ◽

10.1007/s00221-012-3293-3 ◽

2012 ◽

Vol 224 (1) ◽

pp. 125-139 ◽

Cited By ~ 24

Author(s):

Erin L. Zelinski ◽

Amanda V. Tyndall ◽

Nancy S. Hong ◽

Robert J. McDonald

Keyword(s):

Cortical Function ◽

Prefrontal Cortical

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