Effect Of HIV On Neurological System

Today's post from zedie.wordpress.com (see link below) talks about something that is causing arguments for and against across the scientific world. Along with aging more quickly, if you have HIV, the incidence of neurological disorders (including dementia, memory loss, Alzheimers and Parkinsons and of course neuropathy) amongst HIV positive people is said to be both higher and occurs sooner, than in the general population. It's difficult to prove, which is why there are many who disagree but as far as neuropathy is concerned, when 30% to 40% of HIV carriers have neuropathic problems, those are pretty convincing statistics. The problem is that just as many diabetes patients end up with neuropathy, so restricting it to HIV patients is somewhat tenuous.

The Effect of HIV on Neurologic Disorders.
Source: Journal Watch Infectious Diseases Nov.22nd 2012

In a large cohort study, HIV-positive men developed neurologic disorders at an earlier age and more frequently than HIV-negative men.

The incidence of many neurologic complications of HIV infection has fallen dramatically since effective combination antiretroviral therapy (ART) was introduced in 1996. To determine whether HIV infection continues to have an effect on neurologic disorders during the era of combination ART, investigators studied a large cohort of men followed between July 1996 and June 2011 in the Multicenter AIDS Cohort Study.

HIV-positive (n=1862) and HIV-negative (n=2169) men who have sex with men were included in the analyses. In the HIV-positive men, the median CD4 count was 585 cells/mm3, and the average duration of ART use was 10.6 years. The incidence of neurologic disorders was higher in HIV-positive men than in HIV-negative men. The median age of first neurologic diagnosis was 48 in the HIV-positive men compared with 57 in the HIV-negative ones. Peripheral nerve and muscle disorders (the most common diagnoses), nervous system infections, dementia, and seizures were more common in HIV-infected than in HIV-negative men; when only confirmed cases were counted, stroke was not more common in the HIV-infected group. Although this study took place during the era of effective therapy, 21% of HIV-infected patients with a neurologic disorder were not receiving ART at the time of the complication.

Comment: This study suggests that HIV infection may increase the rate — and perhaps accelerate the development — of neurologic disorders. However, the relevance of these findings to patients who are doing well on current therapy is difficult to know. A substantial fraction of patients who developed neurologic complications were not receiving ART, and, of those on treatment, we are not told what proportion had virologic suppression. Moreover, the development of some diagnoses in this study, such as peripheral neuropathy, may have been exacerbated by antiretrovirals that we no longer use (e.g., stavudine, didanosine). Also, because ascertainment of neurologic conditions in this study was based on medical record review, more recently recognized and subtle entities, such as mild neurocognitive disorder, were not included. Nevertheless, this study highlights the importance of following HIV-infected patients closely for neurologic disorders and emphasizes the need to initiate effective ART before such complications develop.

http://zedie.wordpress.com/2012/11/22/the-effect-of-hiv-on-neurologic-disorders/

NEWLY DISCOVERED BRAIN CELLS EXPLAIN A PROSOCIAL EFFECT OF OXYTOCIN

Oxytocin, the body's natural love potion, helps couples fall in love, makes mothers bond with their babies, and encourages teams to work together. Now new research at Rockefeller University reveals a mechanism by which this prosocial hormone has its effect on interactions between the sexes, at least in certain situations. The key, it turns out, is a newly discovered class of brain cells.

"By identifying a new population of neurons activated by oxytocin, we have uncovered one way this chemical signal influences interactions between male and female mice," says Nathaniel Heintz, James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology.

The findings, published today in Cell (October 9), had their beginnings in a search for a new type of interneuron, a specialized neuron that relays messages to other neurons across relatively short distances. As part of her doctoral thesis, Miho Nakajima began creating profiles of the genes expressed in interneurons using a technique known as translating ribosome affinity purification (TRAP) previously developed by the Heintz lab and Paul Greengard's Laboratory of Molecular and Cellular Neuroscience at Rockefeller. Within some profiles from the outer layer of the brain known as the cortex, she saw an intriguing protein: a receptor that responds to oxytocin.

"This raised the question: What is this small, scattered population of interneurons doing in response to this important signal, oxytocin?" Nakajima says. "Because oxytocin is most involved in social behaviors of females, we decided to focus our experiments on females."

To determine how these neurons, dubbed oxytocin receptor interneurons or OxtrINs, affected behavior when activated by oxytocin, she silenced only this class of interneurons and, in separate experiments, blocked the receptor's ability to detect oxytocin in some females. She then gave them a commonly used social behavior test: Given the choice between exploring a room with a male mouse or a room with an inanimate object -- in this case a plastic Lego block -- what would they do? Generally, a female mouse will go for the non-stackable choice. Legos just aren't that interesting to rodents. But Nakajima's results were confusing: Sometimes the mice with the silenced OxtrINs showed an abnormally high interest in the Lego, and sometimes they responded normally.

This led her to suspect the influence of the female reproductive cycle. In another round of experiments, she recorded whether the female mice were in estrus, the sexually receptive phase, or diestrus, a period of sexual inactivity. Estrus, it turned out, was key. Female mice in this phase showed an unusual lack of interest in the males when their receptors were inactivated. They mostly just sniffed at the Lego. There was no effect on mice is diestrus, and there was no effect if the male love interest was replaced with a female. When Nakajima tried the same alteration in males, there was also no effect.

"In general, OxtrINs appear to sit silently when not exposed to oxytocin," says Andreas Görlich, a postdoc in the lab who recorded the electrical activity of these neurons with and without the hormone. "The interesting part is that when exposed to oxytocin these neurons fire more frequently in female mice than they do in male mice, possibly reflecting the differences that showed up in the behavioral tests."

"We don't yet understand how, but we think oxytocin prompts mice in estrus to become interested in investigating their potential mates," Nakajima says. "This suggests that the social computation going on in a female mouse's brain differs depending on the stage of her reproductive cycle."

Oxytocin has similar effects for humans as for mice, however, it is not yet clear if the hormone influences the human version of this mouse interaction, or if it works through a similar population of interneurons. The results do, however, help explain how humans, mice and other mammals respond to changing social situations, Heintz says.

"Oxytocin responses have been studied in many parts of the brain, and it is clear that it, or other hormones like it, can impact behavior in different ways, in different contexts and in response to different physiological cues," he says. "In a general sense, this new research helps explain why social behavior depends on context as well as physiology."