Researchers at the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego have demonstrated that oral administration of a cysteine protease inhibitor, E64d, not only reduces the build-up of β-amyloid (Aβ) in the brains of animal models for Alzheimer’s disease, but also results in a substantial improvement in memory deficit. (More here)
From the news release:
Increased Aβ levels in the brain are associated with the development of memory loss and amyloid plaque, the hallmark of Alzheimer’s disease. Aβ peptides are “cut” out from a larger protein called the amyloid precursor protein (APP) by an enzymatic “scissor” called β-secretase, and aggregate to form plaques in the brain regions responsible for memory.
E64d reduces Aβ by inhibiting the β-secretase “scissors” from “cutting” the APP chain into smaller toxic Aβ peptides. But in this study, the researchers found that the compound actually increases the activity of a protease called BACE1 which, to date, has been regarded as the primary β-secretase. Instead, E64d appears to lower brain Aβ by inhibiting the β-secretase activity of another protease, Cathepsin B.
On the topic of the Anon who asked about ADHD. I was diagnosed with ADHD-PI a few months back and I am 18 and in my second year of uni. My older brother has combined ADHD and was diagnosed with it as a child, and while I had brought it up with my mother once or twice that I thought I could have ADHD she said I didn’t. I was diagnosed more by accident then anything. I was seeing a psychiatrist who is known for treating people with ADHD for other problems when it came out I had it. If you believe you have ADHD, go see your schools psychologist or guidance counsellor. It can’t hurt. If you don’t have it, then it’s something you don’t have to worry about it and if you do have it, then you can get help for it.
In response to anon's ADHD question--I wasn't diagnosed until I was 17 and I was very, very angry because of it. I had been showing symptoms since kindergarten--if not sooner. There are psychologists at school usually, he/she could try approaching them instead of talking to her parents. I tried telling my mom that I was depressed/suicidal in 8th grade and she just laughed at me. Nothing hurts worse that being invalidated by a parent. ADHD is a serious matter and it's not something to be taken lightly. Anon--feel free to check out my blog i've posted quite a few times about my struggle with ADHD.
Thanks for your input. Anon, if you are feeling this way you should really try visiting a doctor…
Hi, I have a question about ADHD. Well I'm a freshman in high school, and I noticed that I matched the signs of ADHD since i read about it like about 3 years ago. I try to tell my parents that i honestly think i may have it, but they don't think so. They say that we would have been able to tell earlier. I was just wondering if that ever happens, where you don't get diagnosed until you're a teenager.
From my understanding, not necessarily. I mean, if your parents have never taken you to the doctor to see if your symptoms might be related to the disorder, it’s hard to tell. And many people get diagnosed as teenagers. My sister was diagnosed when she was in her 20s…
do you think personality characteristics are mostly learned? or through genes?
I believe that when it comes to personality, there’s a definite gene-environment interaction. I believe experience and circumstances shape whatever genetic predisposition we may have. For example, an individual may have genes that are associated w/ personality traits like impulsivity and novelty-seeking, but are raised in a strict and conservative environment where these qualities are not necessarily desirable… What I’m trying to get at is that the environment (society, culture, relationships) selects for some traits, regardless of what biological predisposition you may have.
Also, I’m a firm believer that humans have to ability to choose what they want to be like. For this reason, I feel that personality is both a conscious and unconscious effort.
What is the relationship between social and physical pain?
According to MacDonald and Leary, social pain refers to the emotional reactions that accompany the perception that one is being excluded from a social relationship or being devalued by desired relationship partners or groups. Usually, when people talk about emotional/social pain (social pain is considered by some as a type of emotional pain), they think of the word pain as being an adequate metaphor for hurt feelings. But what if emotional pain caused by social exclusion, rejection and loss, for example, operates through a similar mechanism than physical pain?
MacDonald and Leary (2005) have an interesting hypothesis: reactions to rejection are mediated by aspects of the physical pain system. From an evolutionary perspective, inclusion in social groups is essential for survival (in social animals). Thus, the authors propose that threats to social connections are basically processed and perceived as threats to safety. While this group argues that the aversive state characterized by emotional/social pain is similar to that experienced when going through physical pain, others (Thornhill & Thornhill, 1989) have argued that emotional pain functions in an analogous way to physical pain. They propose that such pain (social) focuses attention on significant social events (that may be important for survival) to promote the correction and avoidance of such future events. Interesting theory, no?
However, evidence supporting the theory of overlap between social and physical pain is abundant. For example, social and physical pain overlap in attitudes and behaviors and these 2 types of pain correlate similarly with factors such as extraversion, social support, anxiety, aggression and depression. Below is some of the evidence of overlap that I found most convincing:
Shared physiological mechanisms: Both types of pain have been shown to involve the anterior cingulate cortex, periaqueductal brain structures, and opioid/oxytocin systems.
The experience of pain consists of 2 components: pain sensation and pain affect. Pain sensation conveys information about actual tissue damage and is processed by specialized mechanoreceptors. Pain affect consists of the unpleasant and negative feelings that typically accompany pain sensation as well as the emotions associated with future implications of those sensations. Emotional pain taps into the pain circuitry indirectly- via the pain affect component.
Emotional pain, like physical pain, can serve to regulate and modify future behavior. Emotional and physical pain may both serve as negative reinforcement that functions to guide the animals to safety. Increases/decreases in pain mark avoidance/approach responses and behaviors, respectively in order to minimize pain.
In the context of learning, specific early life experiences are involved in alleviating both types of pain. In babies, physical pain (hunger) or discomfort (soiled) is usually alleviated by emitting signals (crying, gestures) that elicit a caregiver response. The baby learns that physical (and social) contact may help minimize the pain so babies form attachment relationships. Basically, the baby learns that if it’s alone (socially isolated), it will be in pain (nobody will take care of it). In short, babies make this connection between social and physical pain very early on.
MacDonald and Leary. 2005. Why Does Social Exclusion Hurt? The Relationship Between Social and Physical Pain. The Psychological Bulletin. 131 (2): 202-223. DOI: 10.1037/0033-2909.131.2.202
Related seminal work: Panksepp, J. (1998). Affective neuroscience: The foundations of human and animal emotions. London: Oxford University Press.
hey there, i was wondering how long you've been studying for? and also, at what stage does one become adequately qualified to work in the neuropsych profession?
it's been my dream to be a neuropsychologist for years now, im currently in my final year of highschool and have already had interviews with universities who say that they'd accept me but I'd love to know what studying is like and what topics you look at in the first few years of the course... i'm pretty sure however that the australian system (where i'm from) is quite different to the american system but i'd just love to know your perspective anyhow because i don't know anyone else who is remotely as interested in the subject as i am around here haha...
B.S. Biology = 4 years
Neuroscience and Physiology Ph.D. program=2 years (end of my second year). My NSF grant runs for 3 more years so hopefully it won’t be more than 5 years total for my Ph.D.
Again, I’m not the right person to ask for the neuropsych because I study neuroscience, not neuropsychology.
Studying is hard but it pays off in the end. Just knowing that I can wrap my mind around these complex subjects is enough of payoff for me to be honest.
Hi. I really love your blog and am a prospective applicant into a doctoral neuro program. I am taking the GRE soon (by June) and would appreciate if you can recommend some study material. I was thinking of taking 2 subject tests in biology and psychology along with the general. Does this sound like a good idea? I'd appreciate your input so much (ie. which study materials you used, especially for the general exam as well b/c I'm told that the subject tests are easier) Thanks so much and I'm looking forward to hearing your response!
Hey, thanks :]
I didn’t study much for the GRE. It’s basically just verbal (english) and quantitative (math). I did some practice for the quantitative part. I took some reviews that the SLOAN program back at my home institution paid for. Somebody from Baylor came to help us review…
I also didn’t take any subject tests so I may not be the best person to ask. I’ve asked my friends from grad school what they’ve taken and what they’ve think and the consensus is that the biology one is way more important than the psych one. Both are a good idea, if you are up to it, but are not necessary. For the psych one I would suggest taking one in a subject you master, obviously.
I have gotten so many questions about people who are interested in neuroscience as a career that I have created this post so I can reference back to it in the future.
Note: This is a guide directed towards people that want RESEARCH careers. My graduate program’s approach towards neuroscience integrated knowledge from many areas like electrophysiology, cellular and molecular biology, and computational neurobiology relying on mathematics/physics. Also, a number of you seem to be under the impression that I am studying neuropsych, which I am not. Neuropsych is traditionally a more clinically-oriented branch within neuroscience.
First of all, if you want to become a neuroscientist, you will most likely have to complete formal graduate training in a related branch or field. You have to be ready for this, because it is something that will take a long time. Not to worry though, time flies and if you like what you’re doing you won’t mind…
In college, the most common options are majoring in either biology or psychology. Some schools have a neuroscience or biopsychology major that may be in the biological sciences department or the psych department or even a combination of both. For example, you could major in biology and minor in psych or vice versa… Because neuroscience is an interdisciplinary field, I would recommend taking courses outside your major (especially if you’re in a psych dept). Helpful and attractive courses include: physics, calculus, organic chemistry, biochem, genetics, cell and molecular biology, bioethics, and neuropsych or psych courses. Importantly, some people come from other backgrounds like electrical/computer engineering that are also helpful in areas like electrophysiology, computational neurobiology and neuronal modeling. Thus, a major in biology or psychology is not a MUST but it definitely gives you an advantage.
While in college, it is also important to gain research experience (try volunteering in labs just to learn or for course credit) while maintaining a decent GPA. And by decent I mean higher than 3.5 on a 4.0 scale. Of course, not all is lost if your GPA is below a 3.5. It will just be harder and you might not be regarded as competitive as other students. Mind you, if you have a 4.0 but all your classes are in the soft sciences and you didn’t take challenging courses, you’re in trouble as well… Third year of college (assuming you will graduate in 4 years) is crucial. This is the time to beef up your CV/resume, take the GRE, talk to people who will be your references, and complete your application to graduate schools. Graduate schools have a wide variety of programs (i.e. neurobiology, neuroscience, neuropsych) with different kinds of focus. Look at the curriculum for each program and find one that is well-suited for your interests and career aspirations. Remember to apply early and to ask for fee waivers, if available (I applied to 8 schools and got fee waivers for all but one of them!). Your personal statement is essential. And by that I mean it absolutely has to be good if not great. Different schools have different criteria for this essay and you should remember to pay attention to these criteria and follow instructions. You should also have several people proofread it before you send it. After you submit your application, send an e-mail to make sure everything is complete. If you get an interview, ask who your interviewers will be and familiarize yourself with their research and areas of expertise. Be nice, enthusiastic and ask smart questions. Also, during your interview, highlight why you want to be part of the training environment at that particular university or location and why you’d be a good match for the program and the department. Remember to send thank you e-mail to the faculty that met with you and anybody else you deem appropriate to thank.
Graduate school: Do your best to learn and understand the material presented in your intro classes, as it will be the foundation that most of the other classes will be built upon. You don’t need stellar grades in graduate school, but you do need to pass, which for most universities is a solid B. While you are during your first year, you will most probably rotate through different labs in which you will be able to get to know the lab, learn the techniques and figure out if it’s a good fit for you. After you finish classes, you will be working on your thesis. Most likely, you will need to propose your thesis, select a review committee (composed of experts in fields relating to your research), work in lab and collect data to support your thesis, and defend it. After you defend your thesis, your committee decides your fate. This is the meat of grad school. Work, work, work. Get that thesis out and publishing well. Bonus if you learn how to write grants.
Post-graduate school: Postdoctoral fellowships are a common way of learning additional techniques or addressing a different but related question. Or you could also go into something you don’t know much about. I keep hearing that a postdoc is supposed to add versatility, diversity and publications to your CV. This is also the time period in which you learn how to run a lab, work on your own independent projects, write grants, and decide where you want your career to go (i.e. industry, academia, clinical). Think about it as an extension of your training in which you get more freedom and flexibility.
Alternatively, some people enroll in medical school to pursue an MD degree in addition to the Ph.D. one while others go back to school for other degrees (ex. PsyD, law, etc…). Others find industry jobs or go into public policy.
Hope this helps. If you want to know about something more specific not listed here, contact me.