Natalie Joe, a BSc Honours student in Physiology, was recently awarded the Dean's Prize for the best Summer Studentship in the OSMS.
Natalie's project (Regulation of brain activity in dehydration) was undertaken with Dr Colin Brown and Dr Victoria Scott in the Department of Physiology.
Magnocellular neurosecretory cells are large neurons that are located in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus in the brain.
These neurons synthesise and secrete either one of the hormones, vasopressin or oxytocin, directly into the bloodstream where the hormones exert multiple roles in various areas of the body.
Vasopressin is most commonly known as the hormone that conserves water in the body; it does so by inhibiting urine production by promoting water reabsorption in the kidneys, whereas oxytocin stimulates the secretion of excess sodium.
Both vasopressin and oxytocin have separate but coordinated roles in regulating water and sodium levels, both of which are highly regulated to maintain body fluid balance.
Disorders of body fluid balance are among the most common problems encountered in clinical practice; such disorders increase the risk of death from other medical conditions by 50-fold.
Glial cells are found surrounding neurons including magnocellular neurosecretory cells and have historically been perceived as merely support cells to the adjacent neurons.
However, their roles are much more diverse than originally thought and it is now known that glial cells can undergo plasticity and structural adaptation in varying conditions that the body is placed under, much like neurons.
Glial cells are also able to modulate the activity of nearby neurons and one mechanism that they achieve this is via expression of transporters and channels that help remove glutamate, an excitatory neurotransmitter, from the space around neurons, thereby decreasing the ability of glutamate to act on neurons and decreasing their excitability resulting in a reduced release of vasopressin and oxytocin into the bloodstream.
In this study we investigated the role of these "support cells" in regulating the excitability of SON neurons during chronic dehydration by their contribution to glutamate uptake.
Conducting experiments on anaesthetised virgin female rats, we recorded the activity, or firing rate, of the magnocellular neurosecretory cells in the SON.
These rats were either non-dehydrated (euhydrated) or dehydrated and were administered dihydrokainic acid (DHK), a drug that is a selective inhibitor for the transporters that remove glutamate that are found exclusively on glial cells.
In the presence of DHK, the firing rate of SON neurons increased in euhydrated rats but not dehydrated rats.
This indicates that under basal conditions, where the body fluid composition is within the normal range, glial cells are able to take up glutamate from the space around SON neurons to decrease their excitability.
This is important to prevent inappropriate or over-secretion of oxytocin and vasopressin from these neurons into the blood.
During dehydration, our results indicate that there is a decrease in glial glutamate uptake, increasing the availability of glutamate to the neurons.
This results in an increase in SON excitability to increase vasopressin and oxytocin secretion to defend the organism from further water loss in the urine.
Our study shows that glial cells are not merely support cells, but play an active role in neuronal function by regulating excitability of neurons.
For vasopressin neurons, altered glial regulation of neuronal activity during disorders of body fluid balance might contribute to inappropriate vasopressin neuron responses to rehydration, and thus to inappropriate secretion of vasopressin, leading to an increased risk to patients during treatment.
This research was funded by an Otago School of Medical Sciences Summer Scholarship.
The animal procedures conducted were approved by the University of Otago Animal Ethics Committee.