Behavioural brain research. 2010;209(2):212-20.
Mucopolysaccharidosis IIIB (MPSIIIB) is a lysosomal storage disease characterised
by progressive central nervous system degeneration in patients, with death usually
in the late teens. Serious behavioural problems have been reported in children at
the early stages of the disease, such as hyperactivity and severe sleep disturbances,
which suggest alterations in circadian rhythms. We investigated the circadian rhythm
of locomotor activity of young and old MPSIIIB mice, under a 24-h light-dark (LD)
cycle and under constant darkness (DD), and also examined neuropeptide expression
in the suprachiasmatic nucleus (SCN), site of the principal biological pacemaker.
We show that MPSIIIB mice have higher activity levels during the light (resting) phase
of the LD cycle, together with weaker circadian rhythms, and a longer active phase
due to a late peak of activity, in both LD and DD. In addition, young MPSIIIB mice
showed shorter phase delays in response to a light pulse in DD. Increased lysosomal
storage, neuroinflammation and changes in the expression of Arginine Vasopressin and
Vasointestinal Polypeptide, two circadian neuropeptides, were observed in the SCN,
which may be in part responsible for the changes in circadian behaviour observed in
MPSIIIB mice. These findings suggest an alteration of the circadian system in MPSIIIB
mice, and may inform better clinical management of circadian, sleep and behavioural
disturbances in patients with MPSIII.