Navigation Links
Neuroscientists show insulin receptor signaling regulates structure of brain circuits
Date:6/18/2008

A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated for the first time in living animals that insulin receptors in the brain can initiate signaling that regulates both the structure and function of neural circuits.

The finding suggests a significant role for this class of receptors and perhaps for insulin, not only in brain development, but also in cognition and in pathological processes in which cognition is impaired, as in Alzheimer's disease, for example.

Insulin receptors on the surface of cells throughout the body have long been understood to play a central role in controlling metabolism through the regulation of glucose. When a molecule of insulin, a hormone, "docks" with the receptor, a complex signaling cascade is set in motion inside a cell, culminating in the cell's uptake of insulin.

The Brain Is Not "Insulin-Insensitive" After All

Although insulin receptors are observed in certain parts of the mammalian brain, most scientists, until a few years ago, had assumed the organ was "insulin-insensitive," knowing that glucose could be taken up by brain cells without the involvement of either insulin or insulin receptors.

In recent years, however, it has been shown that the brain is indeed an insulin target, and in cell-culture experiments that insulin receptor signaling in neurons can have an impact on the formation and development of neural circuits. This had never been demonstrated in living organisms until it was shown in experiments performed in the laboratory of CSHL Professor Hollis Cline, Ph.D., and reported this week in the journal Neuron.

These experiments, in Xenopus tadpoles, show that insulin receptor signaling in neurons regulates the maintenance of synapses, contributes to the processing of sensory information and is also involved in adjusting the plasticity of brain circuits in response to experience. The latter function is particularly interesting, notes Dr. Cline, since "it is required for the incorporation of neurons into brain circuits."

Blocking the Receptor

To test the idea that insulin receptor signaling regulates the formation of brain circuits during development, the Cold Spring Harbor team used two different techniques to block the function of the receptor in neurons located in the visual pathway of tadpoles. One method "knocked down" expression of the receptors genetically, while the other left them in place but prevented them from initiating signaling cascades within the cell.

"Tadpoles are wonderful creatures for such experiments," Dr. Cline explained, "in part because they have translucent bodies, which makes it easy for us to visualize and record what happens to individual neurons as we manipulate the insulin receptors on their surface."

When insulin receptor function was blocked, neurons in the visual pathway connecting the tadpole's retina to a brain region called the tectum responded very poorly to light stimuli. The tectum is the area in which brain cells process incoming visual signals. "We showed that the insulin receptor is critical for the proper operation of this circuit, and also that defects in receptor signaling cause a reduction in the animal's visual responses," Dr. Cline said.

Time-Lapse Images of Dendritic Branching

The team went on to perform other experiments that demonstrated two remarkable facts. One is that insulin receptor signaling correlates with the density of the synapses, or neuron-to-neuron connections, in brain circuits. In more technical terms, they found that insulin receptors maintain synaptic density and that synapse density decreases when insulin receptors are removed or dysfunctional.

The team also secured time-lapse images of dendritic formations, the ethereal, branch-like structures that receive chemical signals sent from one neuron to the next. Again, they found that when insulin receptors are engaged and sending signals inside the neuron, dendritic growth is enhanced, specifically in response to visual stimulation.

In this, as in the findings about synaptic density, the team found that insulin receptor signaling regulates the form and function of brain circuits in response to incoming visual information. Another way to put this is that the receptor regulates brain circuits in response to "experience."

Possible Links to Disease

This suggests that insulin receptors in the brain may play a key role not only in the brain's development early in life, but also in disease processes that usually occur late in life. People with advanced diabetes suffer memory loss and cognitive deficits, possibly because insulin receptor signaling in the brain is disrupted, synaptic connections are lost and brain circuits don't work optimally.

In addition, other researchers have found a correlation between diminished insulin receptor signaling and Alzheimer's disease. Results of the Cold Spring Harbor team's research raise the question of whether deficits in learning and memory associated with Alzheimer's might be linked causally to decreased synaptic density as a consequence of lowered insulin receptor signaling. "We are a long way from knowing this for sure, but it's the direction in which our work now takes us," Dr. Cline said.


'/>"/>

Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. QBI neuroscientists make Alzheimers disease advance
2. Jefferson neuroscientists find early lead exposure impedes recovery from brain injury
3. Jefferson neuroscientists show anti-inflammation molecule helps fight MS-like disease
4. Insulin Resistance Tied to Peripheral Artery Disease
5. Some patients may not need insulin for long-term control of type 2 diabetes
6. Novel mechanisms controlling insulin release and fat deposition discovered
7. Photo: Introduction of the Amigo Insulin Pump Offers a Lifestyle Where Life Has No Limits
8. Aspirin-like compounds increase insulin secretion in otherwise healthy obese people
9. Disturbed regulation of insulin production
10. New nanotube sensor can continuously monitor minute amounts of insulin
11. How Patients Can Meet the Criteria for Insulin Pump Therapy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... , ... February 12, 2016 , ... ... devoted exclusively to funding innovative lymphoma research and serving the lymphoma community through ... over 250 members of South Florida’s philanthropic community at its 10th anniversary Fashion ...
(Date:2/12/2016)... ... , ... As a former television executive, owner Tal Rabinowitz knows how stressful ... decompress, Rabinowitz found herself drawn to a casual meditation class while working at NBC ... implementing a 20-minute-per-day meditation practice with her team. After her tenure at NBC, she ...
(Date:2/12/2016)... Miami, FL (PRWEB) , ... February 12, 2016 ... ... Workspace as a Service (WaaS), today announced the integration of Clarity Intelligence Platform ... itopia’s channel partners to offer real-time business intelligence (BI) to their small and ...
(Date:2/12/2016)... ... ... The Jones Agency, a family owned insurance company with offices serving Arlington, Dallas, ... with the Tarrant Area Food Bank in the hopes of alleviating hunger for nearby ... Tarrant County Food Bank offers hope and security to the one in six Texas ...
(Date:2/12/2016)... , ... February 12, 2016 , ... Donor Network West, ... California and Nevada, announced a partnership with San Ramon Regional Medical Center. Under the ... hospital’s facilities as a way to accommodate a more certain time frame for donor ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... -- The primary goal of this research is to ... usage of liquid biopsy. Key information the survey seeks ... of liquid biopsy adoption amidst future users - Predominantly ... - Sample inflow to conduct liquid biopsy tests - ... so on. - Correlation analysis of sample type and ...
(Date:2/11/2016)... SAN FRANCISCO , Feb. 11, 2016  Kindred ... focused on saving and improving the lives of pets, ... Technical Section of the New Animal Drug Application (NADA) ... the pivotal field study (KB0120) of Zimeta for the ... by the Company. --> ...
(Date:2/11/2016)... Feb. 11, 2016 Potrero Medical, Inc., the developer ... announce the appointment of George M. Rapier, III , ... Antonio, TX , WellMed is one of the nation,s ... and HMO members in Texas and ... out of his own internal medicine practice, he has been ...
Breaking Medicine Technology: