posted on 2021-06-17, 17:40authored byJosephine
M. Brown, Lauren S. Baker, Kim B. Seroogy, Mary Beth Genter
Parkinson’s
disease (PD) is a debilitating neurodegenerative
disorder. Early symptoms include motor dysfunction and impaired olfaction.
Toxic aggregation of α-synuclein (aSyn) in the olfactory bulb
(OB) and substantia nigra pars compacta (SNpc) is a hallmark of PD
neuropathology. Intranasal (IN) carnosine (2 mg/d for 8 weeks) was
previously demonstrated to improve motor behavior and mitochondrial
function in Thy1-aSyn mice, a model of PD. The present studies evaluated
the efficacy of IN carnosine at a higher dose in slowing progression
of motor deficits and aSyn accumulation in Thy1-aSyn mice. After baseline
neurobehavioral assessments, IN carnosine was administered (0.0, 2.0,
or 4.0 mg/day) to wild-type and Thy1-aSyn mice for 8 weeks. Olfactory
and motor behavioral measurements were repeated prior to end point
tissue collection. Brain sections were immunostained for aSyn and
tyrosine hydroxylase (TH). Immunopositive cells were counted using
design-based stereology in the SNpc and OB mitral cell layer (MCL).
Behavioral assessments revealed a dose-dependent improvement in motor
function with increasing carnosine dose. Thy1-aSyn mice treated with
2.0 or 4.0 mg/d IN carnosine exhibited fewer aSyn-positive (aSyn(+))
cell bodies in the SNpc compared to vehicle-treated mice. Moreover,
the number of aSyn(+) cell bodies in carnosine-treated Thy1-aSyn mice
was reduced to vehicle-treated wild-type levels in the SNpc. Carnosine
treatment did not affect the number of aSyn(+) cell bodies in the
OB-MCL or the number of TH(+) cells in the SNpc. In summary, intranasal
carnosine treatment decreased aSyn accumulation in the SNpc, which
may underlie its mitigation of motor deficits in the Thy1-aSyn mice.