TY - JOUR
T1 - Circadian rhythm and suprachiasmatic nucleus alterations in the mouse model of mucopolysaccharidosis IIIB
AU - Canal, Maria M.
AU - Wilkinson, Fiona L.
AU - Cooper, Jonathan D.
AU - Ed Wraith, J.
AU - Wynn, Rob
AU - Bigger, Brian W.
N1 - Funding Information:
This work was funded by grants from the UK Society for Mucopolysaccharide Diseases to BWB, and the Research Councils UK and the Biotechnology and Biological Sciences Research Council to MMC. JEW and BWB are supported by the NIHR Manchester Biomedical Research Centre. FLW is funded by the Lady Shauna Gosling Trust. The authors gratefully acknowledge the help and assistance of the staff of the Manchester BSU.
PY - 2010/6/19
Y1 - 2010/6/19
N2 - 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.
AB - 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.
KW - Behaviour
KW - Circadian rhythm
KW - Lysosomal storage disease
KW - MPSIIIB
KW - Mucopolysaccharidosis
KW - Neurodegenerative disease
KW - Sanfilippo
KW - Suprachiasmatic nucleus
KW - Synaptic loss
UR - http://www.scopus.com/inward/record.url?scp=77949261494&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2010.01.045
DO - 10.1016/j.bbr.2010.01.045
M3 - Article
C2 - 20138090
AN - SCOPUS:77949261494
SN - 0166-4328
VL - 209
SP - 212
EP - 220
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -