Introduction-Adverse life events occurring in early development can result in long-term effects on behavioural, physiological and cognitive processes. In particular, perinatal stressors impair neurogenesis in the hippocampus which consequently impairs memory formation. Exercise has previously been shown to have antidepressant effects and to increase cognitive functioning by increasing neurogenesis and neurotrophins in the hippocampus. The current study examined the effects of maternal separation, which has been shown to model anxiety in animals, and the effects of exercise on learning and memory.Methods-Forty-five male Sprague-Dawley rats were divided into 4 groups, maternally separated / non-runners, maternally separated / runners, non-separated / runners and nonseparated / non-runners. Maternal separation occurred from postnatal day 2 (P2) to 14 (P14) for 3 hours per day. Exercised rats were given voluntary access to individual running wheels attached to their cages from P29 to P49. Behavioural testing (Morris water maze (MWM) and object recognition tests) took place from P49 to P63.Results-Maternally separated rats showed no significant difference in anxiety levels in the elevated plus maze and the open field compared to the normally reared controls. However, rats that were allowed voluntary access to running wheels showed increased levels of anxiety in the elevated plus maze and in the open field. Maternal separation did not have any effect on memory performance in the MWM or the object recognition tasks. Exercise increased spatial learning and memory in the MWM with the exercised rats displaying a decreased latency in locating the hidden platform than the non-exercised rats. The exercised rats spent significantly less time exploring the most recently encountered object in the temporal order task in comparison to the non-exercised controls, therefore showing improved temporal recognition memory. All groups performed the same on the other recognition tasks, with all rats showing intact memory performance. Conclusion-Resultsindicate that maternal separation had little effect on the rats whereas exercise enhanced both spatial and recognition memory.
BackgroundExposure to early adverse events can result in the development of later psychopathology, and is often associated with cognitive impairment. This may be due to accelerated cell aging, which can be catalogued by attritioned telomeres. Exercise enhances neurogenesis and has been proposed to buffer the effect of psychological stress on telomere length. This study aimed to investigate the impact of early developmental stress and voluntary exercise on telomere length in the ventral hippocampus (VH) and prefrontal cortex (PFC) of the rat. Forty-five male Sprague–Dawley rats were categorised into four groups: maternally separated runners (MSR), maternally separated non-runners (MSnR), non-maternally separated runners (nMSR) and non-maternally separated non-runners (nMSnR). Behavioural analyses were conducted to assess anxiety-like behaviour and memory performance in the rats, after which relative telomere length was measured using qPCR.ResultsMaternally separated (MS) rats exhibited no significant differences in either anxiety levels or memory performance on the elevated-plus maze and the open field compared to non-maternally separated rats at 49 days of age. Exercised rats displayed increased levels of anxiety on the day that they were removed from the cages with attached running wheels, as well as improved spatial learning and temporal recognition memory compared to non-exercised rats. Exploratory post-hoc analyses revealed that maternally separated non-exercised rats exhibited significantly longer telomere length in the VH compared to those who were not maternally separated; however, exercise appeared to cancel this effect since there was no difference in VH telomere length between maternally separated and non-maternally separated runners.ConclusionsThe increased telomere length in the VH of maternally separated non-exercised rats may be indicative of reduced cellular proliferation, which could, in turn, indicate hippocampal dysfunction. This effect on telomere length was not observed in exercised rats, indicating that voluntary exercise may buffer against the progressive changes in telomere length caused by alterations in maternal care early in life. In future, larger sample sizes will be needed to validate results obtained in the present study and obtain a more accurate representation of the effect that psychological stress and voluntary exercise have on telomere length.
Stress affects the brain differently depending on the timing, duration and intensity of the stressor. Separation from the dam for 3 hours per day is a potent stressor for rat pups which causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, evidenced by increased plasma levels of adrenocorticotropin (ACTH) and glucocorticoids. Behaviourally, animals display anxiety-like behaviour while structurally, changes occur in neuronal dendrites and spines in the hippocampus and prefrontal regions involved in emotion and behaviour control. The aim of the present study was to determine whether maternal separation alters expression of synaptic markers, synaptophysin and calcium/calmodulin-dependent protein kinase II, CaMKII, in rat hippocampus and prefrontal cortex. A second aim was to determine whether voluntary exercise had a beneficial effect on the expression of these proteins in rat brain. Maternal separation occurred from postnatal day 2 (P2) to P14 for 3 hours per day. Exercised rats were housed in cages with attached running wheels from P29 to P49. At P65, the prefrontal cortex and hippocampus were removed for protein quantification. Maternal separation did not have any effect while exercise increased synaptophysin and CaMKII in the ventral hippocampus but not in the dorsal hippocampus or prefrontal cortex. Since the ventral hippocampus is associated with anxiety-related behaviour, these findings are consistent with the fact that voluntary exercise increases anxiety-like behaviour and improves learning and memory.
The prevalence of delirium in acute medical inpatients is high, with estimates ranging from 10% to 31%. [1] Short-and long-term complications of delirium include increased mortality and length of hospitalisation, post-discharge institutionalisation, and long-term functional and cognitive decline. [2] This is a considerable healthcare burden: in developed countries the cost of delirium is equal to that of falls and diabetes mellitus. [3] A number of risk factors for delirium have been identified, including predisposing factors such as dementia and advancing age and acute precipitating factors such as drugs, infections and metabolic abnormalities. [2] Protective factors include a higher level of education, a marker of cognitive reserve. [4] Unfortunately, the data on delirium outcomes and risk factors in general medical inpatients are derived almost exclusively from geriatric populations in developed countries, a very different population to acute medical admissions in developing country settings with a high HIV/tuberculosis (TB) burden. [5] Furthermore, the few studies from developing country settings such as sub-Saharan Africa (SSA) have either been conducted in medical patients aged >60 years or in specialised populations, such as psychiatric and intensive care settings. [6][7][8] In developed countries such as the USA, studies were done among HIV-infected populations before universal access to combination antiretroviral therapy (ART). [9][10][11][12][13][14] HIV targets the central nervous system (CNS) with resultant neurocognitive impairment (NCI), a well-described predisposing risk factor for delirium. Acute and opportunistic infections (OIs), also known risk factors for delirium, occur more commonly with advancing immunosuppression. It is therefore unsurprising that studies have shown high prevalence rates of delirium (3.7 -57%) in HIV-infected populations. [6,[11][12][13] Delirium in HIV is often concomitant with NCI, in 8 -22% of cases. [15] Combination ART both prevents and improves NCI and decreases the incidences of acute and OIs. Widespread access to ART may therefore mitigate delirium risk. It is unclear whether HIV infection remains an independent risk factor for delirium in acute medical admissions in endemic HIV settings with universal ART programmes. [9] Furthermore, in developing country settings such as South Africa (SA), with high This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.
Background: The Cambridge Cognitive Examination-Revised (CAMCOG-R) is a sensitive screening tool for the early diagnosis of dementia in older adults. Overall performance on the CAMCOG-R is influenced by educational attainment. Few studies have, however, examined the association between educational attainment and performance on the individual CAMCOG subscales. We aimed to address this question in a sample from a low-and middle-income country (LAMIC), where resource constraints may have compromised access to, and quality of, education for many older adults. Methods: Participants, all over 60 years of age, were 51 cognitively healthy community-dwelling volunteers and 47 individuals diagnosed with mild-moderate stage Alzheimer's disease (AD). Most participants had some high school education. They were administered the CAMCOG-R under standardized conditions. Results: Within both the control and AD patient groups, there were significant associations between years of completed education and CAMCOG-R total score, MMSE score, and CAMCOG-R Language subscale score. In both groups, level of education was not associated with scores on these subscales: in controls, recent memory, R 2 = .21, p = .055, learning memory, R 2 = .16, p = .398, attention/calculation, R 2 = .19, p = .467, and perception, R 2 = .18, p = .984; in AD patients, recent memory, R 2 = .14, p = .340, learning memory, R 2 = .03, p = .680, perception, R 2 = .09, p = .723, and attention/calculation, R 2 = .19, p = .097. Conclusions: Some CAMCOG-R subscale scores were more strongly associated with educational attainment than others. Importantly, however, performance on the recent memory and learning memory subscales was not affected by education. These subscales are sensitive indicators of amnestic mild cognitive impairment (MCI) and early AD. These subscales may therefore remain valid for use as an AD screening tool in resource-poor healthcare settings.
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