Emerging Role of the Cerebrospinal Fluid – Neuronal Interface in Neuropathology

Vanessa Ochoa, Annalee J. Loeffler and Christie D. Fowler*

Emerging Role of the Cerebrospinal Fluid – Neuronal Interface in Neuropathology

Historically, the function of the Cerebrospinal fluid was considered to be limited
to maintenance of extracellular ion concentrations and to serve as a protective ‘cushion’ during cranial impact.

However, recent advances have revealed that the CSF provides a rich source
of signaling molecules, including growth factors, hormones, proteins, peptides, lipids, glucose,
microRNAs, mRNA, and enzymes.1-5 Indeed, primary CSF removed from the brain is sufficient
to maintain cortical explants and cells in culture without the presence of other factors,6 clearly
demonstrating the extent of micronutrient and growth factor enrichment in this fluid.

Several initial studies of CSF function had suggested that signaling factors present in the CSF mediate
satiety, circadian rhythms, and locomotor behavior.

In these early studies, reinstatement of
feeding behaviour was induced by infusing CSF collected from fasted sheep into the ventricles
of satiated sheep,9 and similarly, CSF collected from sleep-deprived goats increased the duration of sleep and decreased locomotor activity when infused into the ventricles of rats.

These findings indicated that substances present in the CSF can exert a significant
influence on motivated behaviors. More recently, Pedrazzoli and colleagues established
that the peptide orexin (a.k.a., hypocretin) is increased in the CSF during sleep deprivation.

In addition to regulating
arousal and wakefulness, orexin has been implicated in drug reinforcement,
obesity and neurodegenerative diseases, such as Parkinson and Alzheimer’s diseases.

As such altered expression of orexin in the CSF under these physiological conditions
could be a mediating factor for the sleep-related effects in the earlier study7
and may also have additional multifaceted effects
on physiological function.

Neuro Open J. 2015; 2(3): 92-98. doi: 10.17140/NOJ-2-118