Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice

Abstract

Caloric restriction (CR) mitigates neurological damage arising from aging and a variety of other sources, including neuropathology in young adult mice that express single and double transgenic (tg) mutations associated with Alzheimer disease (AD). To evaluate the potential of CR to protect against relatively heavy AD-type pathology, middle-aged (13-14 month-old) mice that co-express two mutations related to familial AD, amyloid precursor protein (APP) and presenilin 1 (PS1), were fed balanced diets with 40% fewer calories than ad libitum-fed controls. Following 18 weeks of treatment, mice were killed and brains processed for quantification of total volume of amyloid-beta (Aβ) in the hippocampal formation and the overlying neocortex. Computerized stereology confirmed that CR reduced the total Aβ volume by about one-third compared to that in age-matched controls. Thus, CR appears to attenuate the accumulation of AD-type neuropathology in two cortical brain regions of middle-aged dtg APP/ PS1 mice. These findings support the view that CR could be a potentially effective, non-pharmacology strategy for reducing relatively heavy Aβ deposition in older adult dtg APP/ PS1 mice, and possibly afford similar protection against the onset and progression of AD in older adult humans.

Evaluation of the Role of Melatonin in Dietary Restriction Effects on Spatial Memory Impairment Induced by Streptozotocin (STZ) in Male Rats

“…Such neuroprotective effects have been demonstrated in some earlier reports (1,2,4,5,7,(28)(29)(30). The precise mechanisms mediating these beneficial effects of diet restriction are still unresolved though many hypotheses have been considered so far.…”

“…Recent studies suggest that DR may enhance brain functions including learning and memory (3)(4), synaptic plasticity (5), and neurogenesis (6). The precise mechanisms mediating such beneficial effects of DR are still unresolved.…”

Postnatal glucocorticoid-induced hypomyelination, gliosis, and neurologic deficits are dose-dependent, preparation-specific, and reversible

“…For the area fraction probe (frame 25 μm × 25 μm; guard zone 2 μm, interframe interval 400 μm), the user clicked on the grid points that touched myelin fibers in sections stained with MBP. The area fraction of myelination was quantified as the ratio of product of the area per point and number of points hitting reference area [a(point)· ΣP ref ] over the product of the area per point and number of points hitting the sampled area [a(point)· ΣP samp ], as reported (Buser et al, 2012; Mouton et al, 2009). Sampling continued until the coefficient of error (CE) was less than 0.10.…”

“…Sampling continued until the coefficient of error (CE) was less than 0.10. To assess gliosis, we determined total volume fraction of astrocyte cell bodies and fibers (Mouton et al, 2009). Volume fraction of astrocytes was quantified in a similar fashion as for myelin.…”

Calorie Restriction, Longevity and Cognitive Function

“…A study in 1997 showed the scatter plot of AD prevalence versus total food supply for countries; it further indicated that for every per capita additional grams of fat or calorie consumed per day, there is an average increase of 0.03% and 0.003%, respectively, in AD prevalence in the adult population of 65 years age or older (7). On the other hand, it has been shown that sustained CR reduces Aβ neuropathology compared with adlibitum feeding in several AD mouse models (11). Previous studies in which CR started in relatively young mice (<7months age) with transgenic APP mutations and relatively light amyloid loads demonstrated that CR blocks the mutation of Aβ-containing amyloid plaques (12).…”