Biology Reference
In-Depth Information
morphogenesis. Additionally, rats with hydrocephalus, and thus impaired CP struc-
ture and function, also have impaired cortical development, suggesting that the fac-
tors in circulating CSF are vital for development
[19]
.
4.5 Choroid Plexus and Aging
As with developmental effects, CP also directly influences aging. In humans, the
height of CP epithelial cells decreases by about 10-11% during life
[20]
. The aged
epithelial-cell cytoplasm becomes rich with Biondi Ring tangles and lipofuscin
deposits
[21]
, and the nuclei appear irregular and flattened as the basement mem-
brane thickens
[20]
. The stroma thickens and collects collagen fibers, hyaline bod-
ies, calcifications, and psammoma bodies, and the infiltrating arteries become thicker
and fragmented
[22,23]
. Analogous aberrant changes occur in aged mouse and rat
choroid epithelial cells
[24,25]
.
Because the overall functions of CP are energy dependent, and with energy
metabolism compromised in aging, the CP cannot maintain its normal energy output
in the aged brain. Synthesis of enzymes needed for anaerobic respiration and oxida-
tive phosphorylation decline in aging rats, with lactate dehydrogenase and succinate
dehydrogenase decreasing 9% and 26%, respectively
[26]
. As a consequence of the
aging-mediated reduction in energy metabolism, there is a surge in the number of
epithelial cells deficient in cytochrome C oxidase, which alters the respiratory mito-
chondrial chain and decreases ATP production
[27]
. Reductions in Na
K
-ATPase
and the Na
K
-2Cl
co-transporter also occur
[28]
. The combined anatomical and
enzymatic deteriorations could lead to a diminution of CSF secretion that translates
to about a 45% decrement in aged animals
[29]
. As a result of reduced secretion and
the simultaneously increased CSF volume caused by brain atrophy, CSF turnover
is significantly longer in elderly rats (7.9 hours) than in young rats (2.2 hours). In
agreement with the aged rat research, CSF production has been reported to dimin-
ish with aging in humans, from 0.41 ml/min at 28 years to 0.19 ml/min at 77 years
[9,22]
. Together with age-related cerebral atrophy, the turnover of CSF decreases to
less than 2 times daily in elderly subjects, versus 3-4 times per day in young adults.
These significant alterations in CP and CSF have been postulated to result in inad-
equate distribution of nutritive substances, additional cellular stress, and reduced
clearance of toxic compounds. The functional consequences of an aged CP are also
recognized at the level of clinical symptoms, including accelerated cognitive and
motor decline and/or the development of certain neurological disorders.
4.6 Choroid Plexus and Neurodegeneration:
Alzheimer's Disease as a Case in Point
In an effort to elucidate the influence of an aging CP on CNS disorder, we discuss
laboratory evidence demonstrating CP alterations in Alzheimer's disease (AD).
The age-related deficiencies of CP are exacerbated in AD, and are characterized
