Objective:This article reviews the potential uses of vestibular stimulation to augment neuroplasticity and cognition in rats through suppressing the AChE activity.
Methods:Rotatory vestibular stimulation was provided in a rotatory vestibular stimulating apparatus at a rate of 50 rpm for 5 minutes, for 30 days for rats. 0.3mg/kg of physostigmine also administered to rats of another group as a standard drug. No rotatory vestibular stimulation or physostigmine is given to the control rats. Biochemical studies were done after vestibular stimulation.
Results:The activity of AChE decreased significantly in rats subjected to vestibular stimulation by rotation when compared with the control.
Conclusion: Rotatory vestibular stimulation enhances neuroplasticity via inhibiting acetyl cholinesterase activity in rats.
People endowed with a prodigious memory generally admit that they use various strategies to improve their cognition. But even if you’re not a memory genius, these common sense strategies can help you forget less often. Various neurological disorders like AD and dementia is related with synaptic loss. In a hypothetical point of view, subjects with AD are able to reacquire
knowledge, and pharmacological modulation of acetylcholine,
norepinephrine and dopamine can influence the maintenance and reformation of neuronal networks. Manipulation of certain neurotransmitters with vestibular stimulation therapy has the potential to promote the maintenance and restoration of the functional connectivity within the semantic networks that are the basis of neuroplasticity . How the release of neurotransmitters occurs is briefly explained in Figure 1.
As an outcome of living in an enriched environment, the
brain of animals undergoes molecular and morphological
changes leading to improvements in learning and memory.
These improvements associate well with intensification in
neurogenesis, synaptic density, or neurotropic factors .
Neural plasticity is continuing in the brain during aging and also
plastic changes occur in young and aged animals as a result of
living in an enriched environment . We highlight the results
from our own laboratory on the dynamics of neurotransmitter
release in the area of the brain confined to cognition. Specifically,
we reviewed the effects of an enriched environment (Vestibular
Stimulation) on the changes in neurons, dendrites and in the
activity of AChE in hippocampus . Acetylcholinesterase
(AChE) or acetyl hydrolase, is the primary cholinesterase in the
body with a very high catalytic activity. It is an enzyme catalyzes
the breakdown of acetylcholine and of some other cholinesters
that function as neurotransmitters.
AChE is found mainly at neuromuscular junctions and in
chemical synapses of the cholinergic type, where its activity
serves to terminate synaptic transmission. Each molecule of
AChE degrades about 25000 molecules of acetylcholine (ACh)
per second, approaching the limit allowed by diffusion of the
substrate [4,5]. Throughout neurotransmission, ACh is released
from the presynaptic neuron into the synaptic cleft and binds to
ACh receptors on the post synaptic membrane, relaying the signal
from the nerve. AChE, also located on the post synaptic membrane,
terminates the signal transmission by hydrolyzing ACh. The
released choline is taken up again by the pre-synaptic neuron
and ACh is synthesized by combining with acetyl CoA through
the action of choline acetyl transferase. A cholinomimetic drug
disrupts this process by acting as a cholinergic neurotransmitter
that is impervious to acetylcholinesterase’s lysing action [6,7].
Vestibular stimulation acts as an environmental enriching
factor and it helps the increased release of neurotransmitters
and also enhances the performance of neurotransmitter like
acetylcholine by inhibiting the activity of AChE, as this is the
enzyme which hydrolyze acetylcholine. Thereby it accelerates the
transmission of action potential through the increased synaptic
connections. The hippocampus is the major center for learning
and memory and is furnished with neurogenesis throughout the
life and firing of two types of hippocampal neurons (place cells
and HD cells) crucial for spatial behavior . Figure 2 shows the
Hippocampal HD cells and Place cells.
Learning a behavioral task or something complicated with
excess physical activity causing the animal to shift away from
homeostasis. This results in consumption of more energy leads
to physiological stress. This in turn leads to the production of free
radicals which will lead to oxidative stress. This can be harmful
for proteins or DNA involved in dendritic growth. This will get
reflected in learning and memory performance also. Enriched
environments and soothing physical activities can be a good
remedy for memory problems and also to enhance learning
and memory via enhancing the production of the required
In our previous papers we have clearly explained about the
vestibular stimulation apparatus which we designed and used in our lab . Schematic Representation of Rotatory Vestibular
Stimulating Apparatus is given in Figure 3.
Rats were randomly divided into different groups comprising
18 rats. Physostigmine (Standard drug) and Rotatory Vestibular
Stimulation were administered to group B and C respectively for
30 days before the beginning of the behavioral task and also 15
minutes prior to the start of acquisition phase as well as each
Group A: Control group (neither Vestibular Stimulation, nor
the drug was administered).
Group B: Standard drug Physostigmine Treated Group
(Rats of Group B were administered with the standard drug
Physostigmine, 0.3mg/kg intraperitoneally)
Group C: Rotatory Vestibular Stimulated Group (RVS).
After 30 days of vestibular stimulation, the rats were
subjected for Behavioral studies in 8 arm Radial arm Maze
(Figure 4). The details of the behavioral experiments were
also published in our earlier papers . For the assessment of
learning and memory the no. of trails taken for attaining the task
were recorded and the we recorded the Long Term Potentiation
(LTP), by subjecting the experimental rats for a retention test
which includes various sessions . Control rats (Group A)
were under gone the same procedure of behavioral task without
providing any drug or vestibular stimulation. The rats of Group
B were administered with the drug physostigmine (0.3mg/kg,
orally) for 30 days without any vestibular stimulation and kept
as standard drug group [10,11].
AChE activity was done by using UV Spectrophotometer by
Ellman et al.  method. Immediately after last retention test,
the rats were sacrificed and the hippocampus was dissected
out in an ice cold 0.1M phosphate buffer saline (pH 7.2). The
hippocampus (10mg/ml) was homogenized in ice cold 0.1M
phosphate buffer saline (pH 7.2) using Teflon homogenizer.
The homogenate was centrifuged at 5000 rpm for 10 min at
40C. The supernatant (0.4ml) mixed with 2.6ml of phosphate
buffer (0.1M, pH 8) and 0.1ml of DTNB (0.01M). After that
0.1ml of acetylthiocholine iodide added, the absorbance was
measured every one minute for 10 minutes at 412nm using
Rate of Acetyl cholinesterase of Group B (5.17±0.71) and C
(5.24±0.55) is significantly decreased when compare with the
Group A (6.87±0.65, p< 0.001). There is no significant difference
between group B and C. From the result it is clear that rate of
AChE activity is reduced in treated groups of rats and this in turn
results in an improved learning and memory. Results shown in
Rotatory Vestibular Stimulation enhances long term
potentiation (LTP). Vestibular nuclei and hippocampus have anatomical connections thus improves cognition because of
the firing of two types of hippocampal neuronal cells (place
cells and HD cells) crucial for spatial behavior. Vestibular
stimulation activates the hippocampal formation and increases
neuronal activity and synaptic connections via increasing
dendritic arborization also. The horizontal semicircular canals
activated by rotation which leads to improved learning and
memory by enhancing the bustle of hippocampus and also by
increasing the level of acetylcholine indirectly by inhibiting
acetylcholinesterase. This can be considered as the root of neural
basis for the improved cognitive functions in the treated rats..