Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease.

Introduction: Physical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD. Similar to AD patients, double-transgenic APPswe/PS1dE9 (APP/PS1) mice exhibit Αß plaques in the cortex and hippocampus, hyperlocomotion, memory deficits, and exacerbated inflammatory response. Therefore, the aim of this study was to investigate the effects of 4 weeks of RE intermittent training on the prevention and recovery from these AD-related neuropathological conditions in APP/PS1 mice. Methods: For this purpose, 6-7-month-old male APP/PS1 transgenic mice and their littermates, negative for the mutations (CTRL), were distributed into three groups: CTRL, APP/PS1, APP/PS1+RE. RE training lasted four weeks and, at the end of the program, the animals were tested in the open field test for locomotor activity and in the object recognition test for recognition memory evaluation. The brains were collected for immunohistochemical analysis of Aß plaques and microglia, and blood was collected for plasma corticosterone by ELISA assay. Results: APP/PS1 transgenic sedentary mice showed increased hippocampal Aß plaques and higher plasma corticosterone levels, as well as hyperlocomotion and reduced central crossings in the open field test, compared to APP/PS1 exercised and control animals. The intermittent program of RE was able to recover the behavioral, corticosterone and Aß alterations to the CTRL levels. In addition, the RE protocol increased the number of microglial cells in the hippocampus of APP/PS1 mice. Despite these alterations, no memory impairment was observed in APP/PS1 mice in the novel object recognition test. Discussion: Altogether, the present results suggest that RE plays a role in alleviating AD symptoms, and highlight the beneficial effects of RE training as a complementary treatment for AD.

Transplantation of inhibitory precursor cells from medial ganglionic eminence produces distinct responses in two different models of acute seizure induction.

Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons during development. Following transplantation in postnatal developing brain, MGE cells can increase local inhibition suggesting a possible protection to GABAergic dysfunction in brain disorders, such as epilepsy. Since it has been shown that MGE-derived cells harvested as neurospheres are able to suppress seizures, it might be important to investigate whether these protective effects would change in different seizure models. Here, we used pentylenetetrazole-(PTZ) and maximal electroshock (MES)-induced seizure models to test whether the transplantation of MGE cells would increase the threshold to trigger acute seizures. When transplanted into the neocortex (layers 3-4) of neonatal mice (postnatal days 3-4), MGE cells were able to survive and were mainly found in piriform cortex, fimbria, and ventricular wall regions. Additionally, the number of GFP+ cells found in the brains of mice induced with PTZ and MES differed significantly and suggests proliferation and larger survival rate of MGE-transplanted cells after PTZ, but not MES-induced seizures. Following transplantation, there was a reduction in the number of animals presenting mild and severe seizures induced by PTZ. Furthermore, MGE-cell transplantation was able to increase threshold to seizures induced by PTZ, but was not able to prevent seizure spread induced by MES.

Maternal deprivation alters growth, food intake, and neuropeptide Y in the hypothalamus of adolescent male and female rats.

Maternal deprivation (MD) for 24 hr during the neonatal period impairs body weight gain in adolescent and adult rats. It has been previously shown that maternally deprived rats consume less standard and carbohydrate-rich diets. Because neuropeptide Y (NPY) is implicated in feeding behavior, we assessed, prospectively, the effects of maternal deprivation, imposed on postnatal days (PND) 3 (DEP3) or 11 (DEP11), on physical development (snout-anal length and body weight gain, measured once a week) and food intake (assessed daily, during the rest and active phases, from PND 23 to PND 51); NPY-immunoreactivity (NPY-ir) in the arcuate nucleus of the hypothalamus was evaluated in male (at PND 52) and female rats in estrous (at PND 53-60). DEP3 and DEP11 male and female adolescents were smaller, lighter, and ate less during the active phase, than their CTL counterparts. This change in food intake was accompanied by reduced NPY-ir in the arcuate nucleus of the hypothalamus. The present results indicate that maternal deprivation had a negative impact on the physical development and feeding behavior of adolescent rats that may be explained by reduced hypothalamic NPY production.