Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes, unique to eukaryotes, that are involved in many facets of cellular regulation. Initial research concentrated on defining the components and organization of MAPK signalling cascades, but recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death.

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Mammalian MAP kinase signalling cascades

2016 Alzheimer's disease facts and figures

The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase This dataset will provide a powerful new resource for understanding the development and function of the brain To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://webstanfordedu/group/barres_lab/brain_rnaseqhtml) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain

https://www.jneurosci.org/content/jneuro/34/36/11929.full.pdf

An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex

This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long‐distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD‐related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2013 for health care, long‐term care, and hospice services for people age 65 years and older with dementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These “long‐distance caregivers” face unique challenges, including difficulty in assessing the care recipient's true health condition and needs, high rates of family disagreement regarding caregiving decisions, and high out‐of‐pocket expenses for costs related to caregiving. Out‐of‐pocket costs for long‐distance caregivers are almost twice as high as for local caregivers.

2013 Alzheimer's disease facts and figures

Mechanisms and functional implications of adult neurogenesis.

Techniques and tools for measuring cognitive ability and/or detecting cognitive impairment or decline For example, techniques and tools are described that can be used to diagnose or test susceptibility to cognitive impairments in children or in elderly people (such as cognitive impairments associated with Alzheimer's Disease) Techniques and tools are described that can be used to evaluate treatment effects and/or measure cognitive decline over time

Object recognition testing tools and techniques for measuring cognitive ability and cognitive impairment

Methamphetamine (MA) has neurotoxic effects on the adult human brain that can lead to deficits in behavior and cognition. However, relatively little research has examined the behavioral or neurotoxic effects of MA in adolescents. The rising rates of adolescent MA use make it imperative that we understand the long-term effects of MA exposure on the adolescent brain and how these effects may differ from those seen in adults. In this study, the long-term effects of MA exposure during early adolescence on behavior and the vasopressin system in the paraventricular nucleus of the hypothalamus in late adolescent and adult male and female C57BL/6J mice were examined. MA exposure increased depression-like behavior in the Porsolt forced swim test in both late adolescent and adult male and female mice. Late adolescent male mice exposed to MA also showed a decrease in the number of vasopressin-immunoreactive neurons in the paraventricular nucleus compared to sex-matched saline-treated controls. Thus, similar to humans exposed to MA during adolescence, mice exposed to MA during adolescence show increased depression-like behavior later in life. These changes in behavior may be related to MA-induced alterations in vasopressin and the hypothalamic-pituitary-adrenal axis, especially in males.

/pdf/long-term-effects-of-early-adolescent-methamphetamine-5d2yz6eqhb.pdf

Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice

The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways. Significant overlap was observed between DNA methylation changes at the 2 and 20-week time points demonstrating specificity and retention of changes in response to radiation. Moreover, a novel class of DNA methylation change was observed following an environmental challenge (i.e. space irradiation), characterized by both increased and decreased 5hmC levels along the entire gene body. These changes were mapped to genes encoding neuronal functions including postsynaptic gene ontology categories. Thus, the brain's response to proton irradiation is both specific and prolonged and involves novel remodeling of non-random regions of the epigenome.

/pdf/bi-directional-and-shared-epigenomic-signatures-following-51c5156o85.pdf

Jacob Raber

Papers

Object recognition testing tools and techniques for measuring cognitive ability and cognitive impairment

Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice

Bi-directional and shared epigenomic signatures following proton and 56 Fe irradiation

Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E.

ApoE isoform modulates effects of cranial 56Fe irradiation on spatial learning and memory in the water maze