So far, we have discussed the BBB permeation
of ingestive peptides with leptin as a major example.
We have discussed the different mechanisms of permeation and trans-BBB signaling,
and the contribution of
circumventricular organs in the crosstalk between the CNS and periphery.
We will now move on to glial biology in feeding and obesity regulation.
Not all astrocytes participate in BBB functions,
but many astrocytes contribute to the BBB with their NP and the basic QD molecules.
In the world of neuroendocrine control of obesity,
neurons initially attracted the most attention.
Gradually, the field is paying more attention to glial cells because
of observed the reactive gliosis changes in astrocytes and microglia.
This is mainly caused by obesity related neuro inflammation.
Our group was among the first to report how obesity
regulates astro acidic leptin receptor or ObR expression,
and how the reactive astrocytes in turn modulated feeding behavior and obesity.
We will elaborate on the regulation of
the astro acidic leptin system in obesity in the following slides.
In the arcuate nucleus of the mice hypothalamus,
immunofluorescence staining of leptin receptor ObR shows two types of cells.
A circular pattern belongs to cell surface and cytoplasm of
neurons as shown by double labeling with a neuronal maker such as new n. Thus,
any pattern shows cellular processes and is expressed by astrocytes as confirmed
by colocalization with an astro acidic marker such as GFP or S100 beta.
In a lean mouse,
there are more neurons expressing leptin receptor in this region,
in an age and sex matched AVY mouse with
adult onset obesity resulting from genetic changes.
There are more ObR positive astrocytes.
Then, C in elite C57B6 mouse.
This provides the first evidence that obesity might up regulate astro acidic ObR.