When Is the Hippocampus Involved in Recognition Memory?

Barker, Gareth R I; Warburton, E. Clea

doi:10.1523/jneurosci.6413-10.2011

Cited by 668 publications

(684 citation statements)

References 41 publications

(43 reference statements)

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“…The behavioral effects of MAP4343 correlated with rescue of the alterations induced by isolation-rearing in α-tubulin isoforms and microtubule dynamics in the hippocampus, amygdala, and PFC. The three brain areas examined are important in all of the behavioral tests used (23)(24)(25) and have been shown to differently respond to stress in terms of alterations in dendritic structure (26). It is possible to speculate that the different effects on microtubule dynamics induced by MAP4343 in the three brain regions are associated with restoration of neuronal integrity and physiological behavioral patterns.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental design. Briefly, male SD rats (postnatal day [21][22][23][24][25] were housed in groups of four per cage (grouped, n = 16) or singly housed (isolated, n = 48) for 40 d. Thereafter, the animals started receiving daily (once a day) injections of treatments as follow: (i) Grouped+Vehicle (control; n = 16); (ii) Isolated+ Vehicle (n = 16); (iii) Isolated+MAP4343 (10 mg/kg; n = 16) and (iv) Isolated+Fluoxetine (10 mg/kg; n = 16). To study the effects of the drugs in relation to the duration of treatments, the animals were split in two cohorts (n = 8 per each treatment group), namely the acute phase cohort with behavioral assays performed between days 1 and 4 of treatment (treatment injection received before behavioral testing), and the subchronic phase cohort with behavioral assays performed between days 7 and 10 of treatment (treatment injection received after behavioral testing).…”

Section: β-Methoxy-pregnenolone (Map4343) As An Innovative Therapeutmentioning

confidence: 99%

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3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

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Section: Discussionmentioning

confidence: 99%

Section: β-Methoxy-pregnenolone (Map4343) As An Innovative Therapeutmentioning

confidence: 99%

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…It remains controversial whether the hippocampus plays a role in recognition memory during the probe trial, with some studies showing that damage to the hippocampus has little effect,32, 33, 34 whereas others show a correlation with impaired performance 35, 36, 37. Because our model does not show major neuropathological abnormalities in the hippocampus apart from mild neuroinflammation, we suggest that major alterations to the brain network caused by axonal shearing in the corpus callosum (which contains nerve fibers connecting one hemisphere to the other) may contribute to disruptions in neuronal communication, impaired cognitive processing and spatial learning, thus driving the poor performance of the r‐mTBI animals.…”

Section: Discussionmentioning

confidence: 99%

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Mouzon

Bachmeier

Ojo

et al. 2017

Ann Clin Transl Neurol

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ObjectiveExposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long‐term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival.MethodsMale C57BL/6J mice (aged 2–3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety‐like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies.ResultsAt 24 months survival animals exposed to r‐mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule‐motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI.InterpretationIn this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.

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“…We used three object memory tasks: novel object recognition, object location, and object-in-place (SI Appendix, Fig. S3), each of which requires different brain regions for optimal performance (18). Obese rats performed poorly on the novel object recognition task, which requires the PRC, compared with normal weight controls (t 12 = 2.343, P = 0.04) (Fig.…”

Section: Significancementioning

confidence: 99%

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

Bocarsly

Fasolino

Kane

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

194

151

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Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses. Here, a rat model of diet-induced obesity was used to explore changes in brain regions important for cognition. Obese rats showed deficits on cognitive tasks requiring the prefrontal and perirhinal cortex. Cognitive deficits were accompanied by decreased dendritic spine density and synaptic marker expression in both brain regions. Microglial morphology was also changed in the prefrontal cortex. Detrimental changes in the prefrontal cortex and perirhinal cortex occurred before metabolic syndrome or diabetes, suggesting that these brain regions may be particularly vulnerable to early stage obesity.O besity is a growing public health concern, affecting more than one-third of the United States adult population (1). Obesity increases the incidence of diabetes, vascular disease, and mental illness, all of which reduce quality of life and place a heavy financial burden on patients and society. Less recognized consequences of obesity are its deleterious effects on cognitive function. Individual cognitive performance, both rudimentary and scholastic, declines with increases in body mass and energy consumption (2-5). These deficits can be observed throughout life, from childhood to late adulthood. Obesity is also associated with an increased incidence of mild cognitive impairment and dementia in the elderly (6).Some evidence suggests that obese individuals have decreased overall brain volume (7), with further studies indicating more specific reductions in the volume of brain regions important for cognition, including the hippocampus, prefrontal cortex (PFC), and anterior cingulate (5,8,9). Few studies, however, have investigated the cellular and biochemical mechanisms that might underlie obesityinduced changes in brain volume and cognitive function.Although clinical studies strongly suggest that obesity produces cognitive impairment and brain atrophy, it is difficult to determine whether these changes arise from obesity itself or from conditions often associated with obesity, like metabolic syndrome, diabetes, and vascular disease. Such conditions, even in the absence of obesity, have been linked to cognitive dysfunction and decreases in brain volume (10-13). Little research has been done exploring the effects of obesity on brain structure and cognition in obese, but otherwise healthy, individuals. To investigate whether obesity in the absence of obvious illness alters brain structure and function, we used a rat model of dietinduced obesity to assess the PFC, the perirhinal cortex (PRC), and the hippocampus...

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When Is the Hippocampus Involved in Recognition Memory?

Cited by 668 publications

References 41 publications

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

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