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.

Role of H3-receptor-mediated signaling in anxiety and cognition in wild-type and Apoe-/- mice

Anxiety and cognition in female histidine decarboxylase knockout (Hdc−/−) mice

Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges.

Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction.

/pdf/methamphetamine-and-the-hypothalamic-pituitary-adrenal-axis-1dh3zfiev7.pdf

Methamphetamine and the hypothalamic-pituitary-adrenal axis

Exposure to methamphetamine during brain development impairs cognition in humans and rodents. In mice, these impairments are greater in females than males. Genetic factors, such as apolipoprotein E genotype, may modulate the cognitive effects of methamphetamine. Methamphetamine-induced alterations in the brain acetylcholine system may contribute to the cognitive effects of methamphetamine and may also be modulated by apolipoprotein E isoform. We assessed the long-term effects of methamphetamine exposure during brain development on cognitive function and muscarinic acetylcholine receptors in mice, and whether apolipoprotein E isoform modulates these effects. Mice expressing human apolipoprotein E3 or E4 were exposed to methamphetamine (5 mg/kg) or saline once a day from postnatal day 11-20 and behaviorally tested in adulthood. Muscarinic acetylcholine receptor binding was measured in the hippocampus and cortex. Methamphetamine exposure impaired novel location recognition in female, but not male, mice. Methamphetamine-exposed male and female mice showed impaired novel object recognition and increased number of muscarinic acetylcholine receptors in the hippocampus. The cognitive and cholinergic effects of methamphetamine were similar in apolipoprotein E3 and E4 mice. Thus, the cholinergic system, but not apolipoprotein E isoform, might play an important role in the long-term methamphetamine-induced cognitive deficits in adulthood.

/pdf/long-term-effects-of-methamphetamine-exposure-on-cognitive-joztdw6ofn.pdf

Jacob Raber

Papers

Role of H3-receptor-mediated signaling in anxiety and cognition in wild-type and Apoe-/- mice

Anxiety and cognition in female histidine decarboxylase knockout (Hdc−/−) mice

Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges.

Methamphetamine and the hypothalamic-pituitary-adrenal axis

Long-term effects of methamphetamine exposure on cognitive function and muscarinic acetylcholine receptor levels in mice.