Current neurobiology最新文献

It is urgent to find the appropriate technology for the early detection of Alzheimer's disease (AD) due to the unknown AD etiopathologies that bring about serious social problems. Early detection of mild cognitive impairment (MCI) has pivotal importance in delaying or preventing the AD onset. Herein, we utilize deep learning (DL) techniques for the purpose of multiclass classification between normal control, MCI, and AD subjects. We used multi-categorical data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) including brain imaging measurements, cognitive test results, cerebrospinal fluid measures, ApoE4 status, and age. We achieved an overall accuracy of 87.197% for our artificial neural network classifier and a similar overall accuracy of 88.275% for our 1D convolutional neural network classifier. We conclude that DL-based techniques are powerful tools in analyzing ADNI data although further method refinements are needed.

Metastatic brain tumors are the most common brain tumors in adults. With numerous successful advancements in systemic treatment of most common cancer types, brain metastasis is becoming increasingly important in the overall prognosis of cancer patients. Brain metastasis of peripheral tumor is the result of complex interplay of primary tumor, immune system and central nervous system microenvironment. Once formed, brain metastases hide behind the blood brain barrier and become inaccessible to chemotherapies that are otherwise successful in targeting systemic cancer. The approval of immune checkpoint inhibitors for several common cancers such as advanced melanoma and lung cancers brings with it the opportunity and obligation to further understand the mechanisms of immunosuppression by tumors that spread to the brain as well as the interaction between the brain environment and tumor microenvironment. In this review paper we define the central role of the immune system in the development of brain metastases. We performed a comprehensive review of the literature to outline the molecular mechanisms of immunosuppression used by tumors and how the immune system interacts with the central nervous system to facilitate brain metastasis. In particular we discuss the tumor-type-specific mechanisms of metastasis of cancers that preferentially metastasize to the brain as well as the therapies that effectively modulate the immune response, such as immune checkpoint inhibitors and vaccines.

The purpose of the present study was to evaluate the impact of sleep disturbances on subsequent depressive symptomatology among a representative sample of patients following traumatic brain injury (TBI). Within a retrospective cohort design, our sample included 305 individuals from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot; NINDS-OD09-004) database. At 3-months post-TBI, symptoms of insomnia were reported by 34% of patients, and symptoms of hypersomnia were reported by 39% of patients. For the vast majority of individuals, sleep complaints were likely to persist through 6-month follow-up. Symptoms of hypersomnia but not insomnia at three months were associated with worsened depressive symptomatology at six months. These results highlight the importance of sleep disturbances in recovery from TBI and suggest targeted sleep treatments as a pathway to improve outcomes and quality of life following TBI.

Background: The presence of Subjective Cognitive Decline (SCD) in the absence of objective change and the inflammatory biomarker Alpha 2 Macroglobulin (A2M) have both been implicated in preclinical Alzheimer's disease. Mexican Americans are population with high rates of cardiovascular and inflammatory disorders.

Objectives: The current study investigated the levels of A2M in cognitively normal Mexican Americans with and without complaints of cognitive decline.

Method: 293 (243 females, 50 males) community-based cognitively normal older Mexican Americans from the ongoing Health and Aging Brain among Latino Elders (HABLE) study were grouped based on subjective cognitive decline and blood samples were assayed by electrochemiluminescence to determine levels of A2M.

Results: Participants with SCD had significantly higher levels of A2M than those without SCD. Females with SCD had a significantly higher level of A2M.

Conclusions: Results suggest that higher levels of A2M, a marker of neuronal injury, may be involved in subtle changes in cognitive functioning recognizable to persons reporting SCD but too subtle to be objectively measured. Longitudinal research is needed to assess the impact of SDC and A2M in progression to MCI and dementia in Mexican Americans.

Mechanisms mediating protective effects of dietary restriction during aging are of great interest since activating such mechanisms protect against a wide range of age-related diseases. In mammals key metabolic responses to nutritional deprivation are mediated by the transcription factor PPAR-alpha, which is activated by free fatty acids and promotes lipid metabolism while inhibiting glucose metabolism. The C. elegans gene nhr-49 appears to function similarly in C. elegans. Here we report that protective effects of dietary restriction and inhibition of glucose metabolism to increase lifespan wild-type C. elegans and reduce toxicity in a polyQ model of Huntington's disease in C. elegans are dependent on NHR-49 and its co-activator CREB-Binding Protein (CBP). We have previously demonstrated that inhibition of cbp blocks protective effects of dietary restriction and blocks the molecular switch from glucose metabolism to alternative substrates. Conversely, increased glucose concentration and inhibition of cbp reduce lifespan and increase proteotoxicity. Lactate and inhibition of ETC complex II mimicked toxic effects of glucose on proteotoxicity whereas pyruvate and inhibition of ETC complex I protected against glucose-enhanced proteotoxicity. These results support that PPAR-alpha-like activity mediates protective effects of dietary restriction by reducing glucose metabolism via reducing production of NADH, and corroborate and extend recent studies demonstrating that PPPAR-alpha agonists increase lifespan in C. elegans dependent on NHR-49.