Background Excessive microglial activation is implicated in the pathogenesis of various age-related neurodegenerative diseases. In addition to neurons, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are also expressed in microglia. However, the direct effect of BDNF on age-related microglial activation has rarely been investigated. Methods We began to address this question by examining the effect of age on microglial activation and the BDNF-TrkB pathway in mice. By using pharmacological and genetic approaches, the roles of BDNF and downstream signaling pathways in microglial activation and related neurotoxicity were examined in microglial cell line and primary microglial cells. Results We showed that microglial activation was evident in the brains of aged mice. The levels of BDNF and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of BDNF. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of BDNF, while shTrkB induced local microglial activation in naïve mice. In cultured microglial cell line and primary microglial cells, BDNF inhibited LPS-induced microglial activation, including morphological changes, activations of p38, JNK, and NF-кB, and productions of proinflammatory cytokines. These effects were blocked by shTrkB. BDNF induced activations of ErK and CREB which then competed with LPS-induced activation of NF-кB for binding to a common coactivator, CREB-binding protein. Conclusions Decreasing BDNF-TrkB signaling during aging favors microglial activation, while upregulation BDNF signaling inhibits microglial activation via the TrkB-Erk-CREB pathway.

Adolescence is a time of developmental changes and reorganization in the brain. It has been hypothesized that stress has a greater neurological impact on adolescents than on adults. However, scientific evidence in support of this hypothesis is still limited. We treated adolescent (4-week-old) and adult (8-week-old) rats with social instability stress for 5 weeks and compared the subsequent structural and functional changes to amygdala neurons. In the stress-free control condition, the adolescent group showed higher fear-potentiated startle responses, larger dendritic arborization, more proximal dendritic spine distribution and lower levels of truncated TrkB than the adult rats. Social instability stress exerted opposite effects on fear-potentiated startle responses in these two groups, i.e., the stress period appeared to hamper the performance in adolescents but improved it in adult rats. Furthermore, whilst the chronic social stress applied to adolescent rats reduced their dendritic field and spine density in basal and lateral amygdala neurons, the opposite stress effects on neuron morphology were observed in the adult rats. Moreover, stress in adolescence suppressed the amygdala expression of synaptic proteins, i.e., full-length TrkB and SNAP-25, whereas, in the adult rats, chronic stress enhanced full-length and truncated TrkB expressions in the amygdala. In summary, chronic social instability stress hinders amygdala neuron development in the adolescent brain, while mature neurons in the amygdala are capable of adapting to the stress. The stress induced age-dependent effects on the fear-potentiated memory may occur by altering the brain-derived neurotrophic factor (BDNF)-TrkB signaling and neuroplasticity in the amygdala.

Background Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3–6 months to induce chronic obesity. Results The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1 + -microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein. Conclusions Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption. Electronic supplementary material The online version of this article (10.1186/s12868-019-0516-6) contains supplementary material, which is available to authorized users.

Background: Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Objective: Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Methods: Young (3 months), middle-aged (9–12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. Results: The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. Conclusion: The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline.

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