Biology Reference
In-Depth Information
6. MECHANISM OF NEUROPROTECTIVE EFFECTS
OF ELECTRICAL ACTIVITY ON CNS
Many studies have been performed to try to determine the mechanism
for activity-dependent neuronal survival. The brain consists of neurons and
glial cells that influence each other and collaborate to keep the brain func-
tional and to perform a wide range of complex tasks. I will review the mech-
anisms of neuroprotection of neuronal activity on the entire CNS.
6.1. Production of neurotrophic factors
Neurons and glia interact to maintain the homeostasis and integrity of the ner-
vous system. Endogenous or exogenous electrical activity activates neurons and
glia to produce neurotrophic agents. Patterned electrical stimulation, which
more closely mimics neuronal activity
in vivo
, is effective in releasing endoge-
nous BDNF from primary sensory neurons (
Balkowiec & Katz, 2000
)andpri-
mary hippocampal neurons (
Brosenitsch&Katz, 2001
). The amount of released
BDNF is regulated by both the stimulus frequency and pattern of electrical stim-
ulation (
Balkowiec & Katz, 2000
). Patterned electrical stimulation depends on
N-type channel and PKA and PKC signaling (
Brosenitsch & Katz, 2001
).
Glial cells control the survival of their associated neurons in both Dro-
sophila and mammals. However, this control is dependent on prior neuronal
triggering of glial cell fate commitment and expression of trophic factors
(
Lemke, 2001
). Glial cells are also able to respond directly to electrical stim-
ulation. Astrocytes align their processes inside an electrical field (
Borgens,
Shi, Mohr, & Jaeger, 1994
), and axon growth can be guided through these
aligned processes
in vitro
(
Alexander, Fuss, &Colello, 2006
). Retinal Mueller
cells, a specialized type of retinal astrocyte, respond to electrical stimulation
by upregulating the expression of neurotrophic factors such as BDNF (
Sato
et al., 2008a
) and IGF-1 (
Morimoto et al., 2005; Sato et al., 2008b
). Thus,
exogenous electrical activity induces the production of neurotrophic factors
by glial cells.
6.2. Neuronal activity controls cerebral blood flow
In addition to the neurons and glial cells, the vascular cells are linked to neu-
ronal functioning through neurovascular coupling. The coupling of the blood
vessel diameter and thus blood flow is related to neuronal activity (
Harder,
Roman, Gebremedhin, Birks, & Lange, 1998
). The nervous system, especially
the brain, is a heterogeneous organ with regionally varied and constantly
